
[Federal Register: November 18, 2009 (Volume 74, Number 221)]
[Rules and Regulations]               
[Page 59607-59686]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18no09-8]                         


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Part II





Environmental Protection Agency





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40 CFR Part 180



Carbofuran; Order Denying FMC's Objections and Requests for Hearing; 
Final Rule


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0162; FRL-8797-6]

 
Carbofuran; Order Denying FMC's Objections and Requests for 
Hearing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Order.

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SUMMARY: In this order, EPA denies objections to, and requests for 
hearing on, a final rule revoking all pesticide tolerances for 
carbofuran under section 408(d) of the Federal Food, Drug, and Cosmetic 
Act (FFDCA). The objections and hearing requests were filed on June 30, 
2009, by the National Corn Growers Association, National Sunflower 
Association, National Potato Council, and FMC Corporation 
(``Petitioners'').

DATES: This final order is effective November 18, 2009.

ADDRESSES: EPA has established a docket for this action under docket 
identification (ID) number EPA-HQ-OPP-2005-0162. To access the 
electronic docket, go to http://www.regulations.gov, and search for the 
docket number. Follow the instructions on the regulations.gov Web site 
to view the docket index or access available documents. All documents 
in the docket are listed in the docket index available in 
regulations.gov. Although listed in the index, some information is not 
publicly available, e.g., Confidential Business Information (CBI) or 
other information whose disclosure is restricted by statute. Certain 
other material, such as copyrighted material, is not placed on the 
Internet and will be publicly available only in hard copy form. 
Publicly available docket materials are available in the electronic 
docket at http://www.regulations.gov, or, if only available in hard 
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac 
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket 
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The Docket Facility telephone number is (703) 
305-5805.

FOR FURTHER INFORMATION CONTACT: Jude Andreasen, Pesticide Re-
evaluation Division (7508P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001; telephone number: (703) 308-9342; e-mail 
address: andreasen.jude@epa.gov.

SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does this Action Apply to Me?

    In this document EPA denies objections and hearing requests by the 
National Corn Growers Association, National Sunflower Association, 
National Potato Council, and FMC Corporation (``Petitioners'') 
concerning EPA's final rule revoking all pesticide tolerances for 
carbofuran. This action may also be of interest to agricultural 
producers, food manufacturers, or pesticide manufacturers. Potentially 
affected entities may include, but are not limited to:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Access Electronic Copies of this Document?

    In addition to accessing an electronic copy of this Federal 
Register document through the electronic docket at http://
www.regulations.gov, you may access this Federal Register document 
electronically through the EPA Internet under the Federal Register 
listings at http://www.epa.gov/fedrgstr. You may also access a 
frequently updated electronic version of EPA's tolerance regulations at 
40 CFR part 180 through the Government Printing Office's pilot e-CFR 
site at http://www.gpoaccess.gov/ecfr.

C. Acronyms

    The following is a list of acronyms used in this order:

AChE--Acetylcholinesterase
aPAD--Acute Population Adjusted Dose
BMD--Bench Mark Dose
BMDL--Bench Mark Dose Level
CCA--Comparative Cholinesterase Assay
CNS--Central Nervous System
CRA--Cumulative Risk Assessment
CSFII--Continuing Survey of Food Intakes by Individuals
CWA--Clean Water Act
CWS--Community Water System
DEEM-FCID--Dietary Exposure Evaluation Model-Food Commodity Intake 
Database
ECG--Electrocardiogram
EDWC--Estimated Drinking Water Concentration
EPA--Environmental Protection Agency
FACA--Federal Advisory Committee Act
FDA--Food and Drug Administration
FIFRA--Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA--Federal Food, Drug, and Cosmetic Act
FQPA--Food Quality Protection Act of 1996
HSRB--Human Studies Review Board
HUC-8--8-digit hydrologic unit code
IRED--Interim Reregistration Eligibility Decision
LD50--Lethal Dose for 50% of a population
LOAEL--Lowest Observable Adverse Effect Level
NAWQA--National Water Quality Assessment Program
NHEERL--National Health and Environmental Effects Laboratory
NMC CRA--N-Methyl Carbamate Cumulative Risk Assessment
NOAEL--No Observable Adverse Effect Level
NOIC--Notice of Intent to Cancel
NRDC--National Resources Defense Council
OP--Organophosphate
ORD--Office of Research and Development
PAD--Population Adjusted Dose
PCA--Percent Cropped Area
PCT--Percent Crop Treated
PDP--Pesticide Data Program
PND--Post-Natal Day
PNS--Peripheral Nervous System
PoD--Point of Departure
ppb--parts per billion
ppm--parts per million
PRZM-EXAMS--Pesticide Root Zone Model-Exposure Analysis Model System
RBC--red blood cell
RED--Reregistration Eligibility Decision
RfD--Reference Dose
SAP--Scientific Advisory Panel
SDWA--Safe Drinking Water Act
USDA--United States Department of Agriculture
USGS--United States Geological Survey
WARP--Watershed Regression for Pesticides

II. Introduction

A. What Action Is the Agency Taking?

    Exposure to the pesticide carbofuran resulting from existing legal 
uses is unsafe--unsafe for the general

[[Page 59609]]

population, and particularly unsafe for infants and children. EPA 
reached this conclusion in 2006 after an exhaustive multi-year review 
of the data on carbofuran as part of its effort to determine whether 
carbofuran should be reregistered under the Federal Insecticide, 
Fungicide, and Rodenticide Act (``FIFRA''), and whether the tolerances 
allowing carbofuran residues on certain foods met the revised safety 
standard in section 408 of the FFDCA. This multi-year review included 
multiple opportunities for public participation, including no less than 
four formal public comment periods. Following EPA review of yet more 
carbofuran data submitted by FMC, the carbofuran registrant, and the 
review of EPA's science findings by the FIFRA Scientific Advisory Panel 
(SAP)--an independent scientific peer review panel--EPA again reached 
the same conclusion in its July 31, 2008 proposal to revoke the 
carbofuran tolerances (73 FR 44864 (July 31, 2008)). In response to 
this proposed revocation, FMC submitted comments challenging many of 
EPA's science findings and also requesting the cancellation of the 
registration of carbofuran on several crops and the restriction of 
where, and the manner in which, carbofuran could be used in the United 
States on its remaining registered crop sites. Finding FMC's science 
arguments to be flawed and its proposed amendments to the carbofuran 
registration to be insufficient, EPA finalized the rule revoking 
carbofuran tolerances on May 15, 2009 (74 FR 23046 (May 15, 2009)).
    Pursuant to the procedures of the FFDCA, on June 29, 2009 
objections to the final revocation rule were filed by the National Corn 
Growers Association, National Sunflower Association, National Potato 
Council, and FMC Corporation (``Petitioners''). The Petitioners also 
requested a hearing on their objections. Coupled with these objections, 
FMC filed on the same day yet another series of proposed amendments to 
its carbofuran registration. These proposed modifications contained new 
application and geographic restrictions as well as an unprecedented 
non-governmental scheme for preventing the use of carbofuran in any one 
area of the country above a small percentage of that area's 
agricultural acreage. The Petitioners relied on these proposed 
carbofuran registration amendments as central to, and inextricably 
intertwined with, their objection to EPA's prior determination in the 
final rule that carbofuran tolerances are unsafe. Specific challenges 
raised by the Petitioners involved EPA's decision on the appropriate 
level of the additional safety factor to protect infants and children, 
EPA's estimate of carbofuran levels in drinking water, EPA's 
consideration of the time needed to recover from exposure to 
carbofuran, and EPA's refusal to consider a human toxicity study 
conducted with carbofuran.
    Today's order denies all of the Petitioners' objections and 
requests for hearing. A principal flaw in the Petitioners' objections 
is that they have objected to EPA's determination in the final rule on 
the safety of carbofuran based on the FIFRA registration amendments 
that FMC filed with EPA 45 days after the safety determination was 
made. As such, the Petitioners' objections are irrelevant, and thus 
immaterial, to the determination EPA made in the final rule. FMC has 
the statutory right under FIFRA to request amendment of its carbofuran 
registration. What Petitioners may not do is prolong the FFDCA 
tolerance revocation process by challenging EPA's safety determination 
based on proposed FIFRA registration changes not before EPA at the time 
of its final revocation decision.
    It should be noted that EPA's decision on the carbofuran tolerances 
is not a determination on FMC's proposed registration amendments. FMC 
may continue to pursue these amendments and also the re-establishment 
of carbofuran tolerances in light of the amendments. Further, FMC may 
seek administrative review, and potentially an administrative hearing, 
with regard to any adverse decision issued by EPA on its proposed 
amendments. But that process must be played out in the future, a future 
in which any decision about the safety of carbofuran is made prior to 
the re-introduction of carbofuran residues in food and water, rather 
than concurrent with the continued exposure of infants and children to 
levels of carbofuran residues that EPA has found to be unsafe.
    Despite the fact that a central aspect of the Petitioners' 
objections is based on a flawed conception of the objection process 
(i.e., the notion that the objection process presents the opportunity 
for a complete reformulation of the matter in dispute, rather than a 
chance for a review of the accuracy of EPA's earlier determination), 
EPA has undertaken a comprehensive analysis of the merits of each of 
the Petitioners' objections and hearing requests. That analysis shows, 
as is exhaustively set out in Unit VI, that none of the Petitioners' 
requests for hearing meets the regulatory standard for granting a 
hearing and none of the Petitioners' objections has merit. There are 
numerous reasons for these conclusions, but two related themes running 
throughout EPA's analysis are the Petitioners' failure to timely raise 
issues or submit supporting documents during the public comment process 
on the proposed rule and the Petitioners' failure to object to how EPA, 
in the final rule, resolved the issues the Petitioners did raise in the 
comment process. EPA considers issues untimely raised to be waived--as 
EPA clearly warned at the proposal stage--and finds recycled comments 
on the proposed rule to be irrelevant to the detailed determinations 
made in the final rule. The rulemaking phase of the revocation process 
has a purpose, and parties treat it lightly at their peril. Finally, 
EPA notes that an additional problem with the Petitioners' objections 
is that once the newly proposed registration amendments are stripped 
from the objections, it is not at all clear that any remaining issues, 
even if concluded in the Petitioners' favor, would result in lowering 
carbofuran's estimated risks--which EPA has estimated as far exceeding 
the safety standard--to an acceptable level. For all of these reasons, 
the Petitioners' objections and hearing requests are denied.

B. What Is the Agency's Authority for Taking This Action?

    EPA is taking this action pursuant to the authority in FFDCA 
section 408(g)(2)(C), which requires the Agency to issue a final order 
resolving the objections to its final rule, issued pursuant to 
408(b)(1)(b), 408(b)(2)(A), and 408(e)(1)(A). 21 U.S.C. 346a(b)(1)(b), 
(b)(2)(A), (e)(1)(A), (g)(2)(C).)

III. Statutory and Regulatory Background

    In this Unit, EPA provides background on the relevant statutes and 
regulations governing the Petitioners' objections and requests for 
hearing as well as on pertinent Agency policies and practices.

A. FFDCA/FIFRA and Applicable Regulations

    1. In general. EPA establishes maximum residue limits, or 
``tolerances,'' for pesticide residues in food under section 408 of the 
FFDCA (21 U.S.C. 346a). Without such a tolerance or an exemption from 
the requirement of a tolerance, a food containing a pesticide residue 
is ``adulterated'' under section 402 of the FFDCA and may not be 
legally moved in interstate commerce (21 U.S.C. 331,

[[Page 59610]]

342). Monitoring and enforcement of pesticide tolerances are carried 
out by the U.S. Food and Drug Administration (``FDA'') and the U.S. 
Department of Agriculture (``USDA''). Section 408 was substantially 
rewritten by the Food Quality Protection Act of 1996 (``FQPA''), which 
added the provisions discussed below establishing a detailed safety 
standard for pesticides, additional protections for infants and 
children, and the process for establishing or revoking tolerances (Pub. 
L. 104-170, 110 Stat. 1489 (1996)).
    EPA also regulates pesticides under the Federal Insecticide, 
Fungicide, and Rodenticide Act (``FIFRA'') (7 U.S.C. 136 et seq.). 
While the FFDCA authorizes the establishment of legal limits for 
pesticide residues in food, FIFRA requires the approval of pesticides 
prior to their sale and distribution (7 U.S.C. 136a(a)), and 
establishes a registration regime for regulating the use of pesticides. 
FIFRA regulates pesticide use in conjunction with its registration 
scheme by requiring EPA review and approval of pesticide labels and 
specifying that use of a pesticide inconsistent with its label is a 
violation of federal law (7 U.S.C. 136j(a)(2)(G)). In the FQPA, 
Congress integrated action under the two statutes by requiring that the 
safety standard under the FFDCA be used as a criterion in FIFRA 
registration actions as to pesticide uses that result in dietary risk 
from residues in or on food (7 U.S.C. 136(bb)), and directing that EPA 
coordinate, to the extent practicable, revocations of tolerances with 
pesticide cancellations under FIFRA. (21 U.S.C. 346a(l)(1)).
    2. Safety standard for pesticide tolerances. Section 
408(b)(2)(A)(i) of the FFDCA requires EPA to modify or revoke a 
tolerance if EPA determines that the tolerance is not ``safe'' (21 
U.S.C. 346a(b)(2)(A)(ii)). Section 408(b)(2)(A)(ii) of the FFDCA 
defines ``safe'' to mean that ``there is a reasonable certainty that no 
harm will result from aggregate exposure to the pesticide chemical 
residue, including all anticipated dietary exposures and all other 
exposures for which there is reliable information.'' This includes 
exposure through drinking water and in residential settings, but does 
not include occupational exposure. Section 408(b)(2)(D) directs EPA, in 
making a safety determination, to:
    Consider, among other relevant factors--* * *
    (vi) Available information concerning the aggregate exposure levels 
of consumers (and major identifiable subgroups of consumers) to the 
pesticide chemical residue and to other related substances, including 
dietary exposure under the tolerance and all other tolerances in effect 
for the pesticide chemical residue, and exposure from other non-
occupational sources;

EPA must also consider, in evaluating the safety of tolerances, 
``safety factors which * * * are generally recognized as appropriate 
for the use of animal experimentation data.'' (21 U.S.C. 
346a(b)(2)(D)(ix).)
    Risks to infants and children are given special consideration. 
Specifically, section 408(b)(2)(C) states that EPA:


    Shall assess the risk of the pesticide chemical based on--* * *
    (II) Available information concerning the special susceptibility 
of infants and children to the pesticide chemical residues, 
including neurological differences between infants and children and 
adults, and effects of in utero exposure to pesticide chemicals;

    (21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)). This provision also 
creates a presumptive additional safety factor for the protection of 
infants and children. Specifically, it directs that ``[i]n the case of 
threshold effects, * * * an additional tenfold margin of safety for the 
pesticide chemical residue and other sources of exposure shall be 
applied for infants and children to take into account potential pre- 
and post-natal toxicity and completeness of the data with respect to 
exposure and toxicity to infants and children'' (21 U.S.C. 
346a(b)(2)(C)). EPA is permitted to ``use a different margin of safety 
for the pesticide chemical residue only if, on the basis of reliable 
data, such margin will be safe for infants and children'' (Id.). The 
additional safety margin for infants and children is referred to 
throughout this order as the ``children's safety factor.''
    3. Procedures for establishing, amending, or revoking tolerances. 
Tolerances are revoked by rulemaking under the unique procedural 
framework set forth in the FFDCA. Section 408(e) of the FFDCA, 21 
U.S.C. 346a(e), authorizes EPA to modify or revoke tolerances on its 
own initiative.
    In issuing a regulation on its own initiative, EPA must first 
publish a notice of proposed rulemaking, and must generally provide at 
least 60 days to allow the public to comment on the proposed 
regulation. After considering comments submitted during this comment 
period, EPA issues a final rule.
    Once EPA issues a final rule, any person may file objections with 
EPA and, if desired, request an evidentiary hearing on those objections 
(21 U.S.C. 346a(g)(2)). Objections must specify ``with particularity 
the provisions of the regulation * * * deemed objectionable and stating 
reasonable grounds therefore'' (21 U.S.C. 346a(g)(2)(A); 40 CFR 
178.25(a)). Objections and hearing requests must be filed within 60 
days (Id.). The statute provides that EPA shall ``hold a public 
evidentiary hearing if and to the extent the Administrator determines 
that such a public hearing is necessary to receive factual evidence 
relevant to material issues of fact raised by the objections'' (21 
U.S.C. 346a(g)(2)(B)). EPA regulations make clear that hearings will 
only be granted where it is shown that there is ``a genuine and 
substantial issue of fact;'' the requestor has identified evidence 
``which, if established, will resolve one or more of such issues in 
favor of the requestor,'' and the issue is ``determinative'' with 
regard to the relief requested (40 CFR 178.32(b)). After consideration 
of any objections, EPA must issue a final order stating the action 
taken in response to each objection, including a determination as to 
whether any hearing is appropriate (21 U.S.C. 346a(g)(2)(C)). The final 
order also establishes any revisions to the final regulation EPA deems 
to be warranted based on the objections. Id. EPA's final order on the 
objections is subject to judicial review in the Court of Appeals, 
within 60 days of the publication of the order (21 U.S.C. 346a(h)(1)).
    4. Tolerance reassessment and FIFRA reregistration. EPA revoked the 
carbfuran tolerances to implement the Agency's findings made during the 
reregistration and tolerance reassessment processes.
    The FQPA required that EPA reassess the safety of all pesticide 
tolerances existing at the time of its enactment. (21 U.S.C. 346a(q)). 
EPA was given 10 years to reassess the approximately 10,000 tolerances 
in existence in 1996. In this reassessment, EPA was required to review 
existing pesticide tolerances under the new ``reasonable certainty that 
no harm will result'' standard set forth in section 408(b)(2)(A)(i). 
(21 U.S.C. 346a(b)(2)(A)(i)). This reassessment was substantially 
completed by the August 3, 2006 deadline. Tolerance reassessment was 
generally handled in conjunction with a similar program involving 
reregistration of pesticides under FIFRA. (7 U.S.C. 136a-1). 
Reassessment and reregistration decisions were generally combined in a 
document labeled a Reregistration Eligibility Decision (RED).

[[Page 59611]]

B. EPA's Human Research Rule

    EPA decisions regarding the use of human studies in pesticide 
regulatory decisions are governed by the Protection for Subjects in 
Human Research final rule (``Human Research rule''), which 
significantly strengthened and expanded protections for subjects of 
human research (71 FR 6138 (February 6, 2006)). The framework of the 
Human Research rule rests on the basic principle that EPA will not, in 
its actions, rely on data derived from unethical research. The rule 
divides studies involving intentional dosing of human subjects into two 
groups: ``new'' studies--those initiated after April 7, 2006 (the 
effective date of the rule)--and ``old'' studies--those initiated 
before April 7, 2006. The Human Research Rule forbids EPA from relying 
on data from any ``new'' study, unless EPA has adequate information to 
determine that the research was conducted in substantial compliance 
with the ethical requirements contained therein (40 CFR 26.1705). These 
ethical rules are derived primarily from the ``Common Rule,'' (40 CFR 
part 26), a rule setting ethical parameters for studies conducted or 
supported by the federal government. In addition to requiring informed 
consent and protection of the safety of the subjects, among other 
things, the rule specifies that ``[r]isks to subjects [must be] 
reasonable in relation to * * * the importance of the knowledge that 
may reasonably be expected to result [from the study].'' (40 CFR 
26.1111(a)(2)). In other words, a study would be judged unethical if it 
did not have scientific value outweighing any risks to the test 
subjects.
    As to ``old'' studies, the Human Research Rule forbids EPA from 
relying on such data if there is clear and convincing evidence that the 
conduct of the research was fundamentally unethical or significantly 
deficient with respect to the ethical standards prevailing at the time 
the research was conducted (40 CFR 26.1704). EPA has indicated that in 
evaluating ``the ethical standards prevailing at the time the research 
was conducted'' it will consider the Nuremburg Code, various editions 
of the Declaration of Helsinki, the Belmont Report, and the Common 
Rule, as among the standards that may be applicable to any particular 
study (71 FR at 6161). Further, reflecting the concern that 
scientifically invalid data are ``always unethical,'' (71 FR at 6160), 
the rule limits the human research that can be relied upon by EPA to 
``scientifically valid and relevant data'' (40 CFR 26.1701).
    Whether the data are ``new'' or ``old,'' the Human Research rule 
forbids EPA from relying on data from any study involving intentional 
exposure of pregnant women, fetuses, or children subject to a very 
limited exception (40 CFR 26.1703, 1706).
    To aid EPA in making scientific and ethical determinations under 
the Human Research rule, the rule established an independent Human 
Studies Review Board (HSRB) to review both proposals for new research 
(new studies) and reports of completed human research (old studies) on 
which EPA proposes to rely (40 CFR 26.1603). The rule directs that the 
HSRB shall be comprised of non-EPA employees ``who have expertise in 
fields appropriate for the scientific and ethical review of human 
research, including research ethics, biostatistics, and human 
toxicology'' (40 CFR 26.1603(a)). If EPA decides to rely on the results 
from ``old'' research conducted to identify or measure a toxic effect, 
EPA must submit the results of its assessment to the HSRB for 
evaluation of the ethical and scientific merit of the research (40 CFR 
26.1602(b)(2)).
    EPA has established the HSRB as a federal advisory committee under 
the Federal Advisory Committee Act (FACA) to take advantage of ``the 
benefits of the transparency and opportunities for public 
participation'' that accompany a FACA committee (71 FR at 6156). The 
HSRB, as appointed by EPA, contains approximately 16 distinguished 
experts in the fields of bioethics, biostatistics, human health risk 
assessment and human toxicology, primarily from academia (Ref. 10).

IV. EPA's Approach to Dietary Risk Assessment

    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. A short summary is provided 
below to aid the reader. For further discussion of the regulatory 
requirements of section 408 of the FFDCA and a complete description of 
the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/
1999/January/Day-04/p34736.htm.
    To assess the risk of a pesticide tolerance, EPA combines 
information on pesticide toxicity with information regarding the route, 
magnitude, and duration of exposure to the pesticide. The risk 
assessment process involves four distinct steps: (1) Identification of 
the toxicological hazards posed by a pesticide; (2) determination of 
the exposure ``level of concern'' for humans; (3) estimation of human 
exposure; and (4) characterization of human risk based on comparison of 
human exposure to the level of concern.

A. Hazard Identification and Selection of Toxicological Endpoint

    1. In General. Any risk assessment begins with an evaluation of a 
chemical's inherent properties, and whether those properties have the 
potential to cause adverse effects (i.e., hazard identification). EPA 
then evaluates the hazards to determine the most sensitive and 
appropriate adverse effect of concern, based on factors such as the 
effect's relevance to humans and the likely routes of exposure.
    Once a pesticide's potential hazards are identified, EPA determines 
a toxicological level of concern for evaluating the risk posed by human 
exposure to the pesticide. In this step of the risk assessment process, 
EPA essentially evaluates the levels of exposure to the pesticide at 
which effects might occur. An important aspect of this determination is 
assessing the relationship between exposure (dose) and response (often 
referred to as the dose-response analysis). In evaluating a chemical's 
dietary risks EPA uses a reference dose (RfD) approach, which involves 
a number of considerations including:
     A `point of departure' (PoD)--the value from a dose-
response curve that is at the low end of the observable data and that 
is the dose that serves as the `starting point' in extrapolating a risk 
to the human population;
     An uncertainty factor to address the potential for a 
difference in toxic response between humans and animals used in 
toxicity tests (i.e., interspecies extrapolation);
     An uncertainty factor to address the potential for 
differences in sensitivity in the toxic response across the human 
population (i.e., intraspecies variability); and
     The need for an additional safety factor to protect 
infants and children, as specified in FFDCA section 408(b)(2)(C).
    EPA uses the chosen PoD to calculate a safe dose or RfD. The RfD is 
calculated by dividing the chosen PoD by all applicable safety or 
uncertainty factors. Typically in EPA risk assessments, a combination 
of safety or uncertainty factors providing at least a hundredfold 
(100X) margin of safety is used: 10X to account for interspecies 
extrapolation and 10X to account for intraspecies variability. Further, 
as required by FFDCA section 408(b)(2)(C), in evaluating the dietary 
risks for pesticide chemicals, an additional safety factor of 10X is 
presumptively applied to protect infants and children, unless reliable 
data support selection of a different

[[Page 59612]]

factor. In implementing FFDCA section 408, EPA also calculates a 
variant of the RfD referred to as a Population Adjusted Dose (PAD). A 
PAD is the RfD divided by any portion of the children's safety factor 
that does not correspond to one of the traditional additional 
uncertainty/safety factors used in general Agency risk assessment. The 
reason for calculating PADs is so that other parts of the Agency, which 
are not governed by FFDCA section 408, can, when evaluating the same or 
similar substances, easily identify which aspects of a pesticide risk 
assessment are a function of the particular statutory commands in FFDCA 
section 408. For acute assessments, the risk is expressed as a 
percentage of a maximum acceptable dose or the acute PAD (i.e., the 
acute dose which EPA has concluded will be ``safe''). As discussed 
below in Unit V.C., dietary exposures greater than 100 percent of the 
acute PAD are generally cause for concern and would be considered 
``unsafe'' within the meaning of FFDCA section 408(b)(2)(B). Throughout 
this document general references to EPA's calculated safe dose are 
denoted as an acute PAD, or aPAD, because the relevant point of 
departure for carbofuran is based on an acute risk endpoint.
    2. Acetylcholinesterase Inhibition. Carbofuran is a member of the 
class of pesticides called N-methyl carbamates (NMCs). The primary 
toxic effect caused by NMCs, including carbofuran, is neurotoxicity 
resulting from inhibition of the enzyme acetylcholinesterase (AChE). 
The toxicity profile of these pesticides is characterized by rapid time 
to onset of effects followed by rapid recovery (minutes to hours). 
Consistent with its mechanism of action, toxicity data on AChE 
inhibition from laboratory rats provide the basis for deriving the PoD 
for carbofuran.
    AChE inhibition is a disruption of the normal process in the body 
by which the nervous system chemically communicates with muscles and 
glands. Communication between nerve cells and a target cell (i.e., 
another nerve cell, a muscle fiber, or a gland) is facilitated by the 
chemical, acetylcholine. When a nerve cell is stimulated it releases 
acetylcholine into the synapse (or space) between the nerve cell and 
the target cell. The released acetylcholine binds to receptors in the 
target cell, stimulating the target cell in turn. As EPA has explained, 
``the end result of the stimulation of cholinergic pathway(s) includes, 
for example, the contraction of smooth (e.g., in the gastrointestinal 
tract) or skeletal muscle, changes in heart rate or glandular secretion 
(e.g., sweat glands) or communication between nerve cells in the brain 
or in the autonomic ganglia of the peripheral nervous system.'' (Ref. 
78 at 10).
    AChE is an enzyme that breaks down acetylcholine and terminates its 
stimulating action in the synapse between nerve cells and target cells. 
When AChE is inhibited, acetylcholine builds up prolonging the 
stimulation of the target cell. This excessive stimulation potentially 
results in a broad range of adverse effects on many bodily functions 
including muscle cramping or paralysis, excessive glandular secretions, 
or effects on learning, memory, or other behavioral parameters. 
Depending on the degree of inhibition these effects can be serious, 
even fatal.
    EPA's cholinesterase inhibition policy statement explains EPA's 
approach to evaluating the risks posed by AChE-inhibiting pesticides 
such as carbofuran (Ref. 78 at 10). The policy focuses on three types 
of effects associated with AChE-inhibiting pesticides that may be 
assessed in animal and human toxicological studies: (1) Physiological 
and behavioral/functional effects; (2) AChE inhibition in the central 
and peripheral nervous system; and (3) AChE inhibition in red blood 
cells and blood plasma. The policy discusses how such data should be 
integrated in deriving an acceptable dose (RfD/PAD) for a AChE-
inhibiting pesticide.
    After clinical signs or symptoms, AChE inhibition in the nervous 
system provides the next most important endpoint for evaluating AChE-
inhibiting pesticides. Although AChE inhibition in the nervous system 
is not itself regarded as a direct adverse effect, it is ``generally 
accepted as a key component of the mechanism of toxicity leading to 
adverse cholinergic effects'' (Id. at 25). As such, the policy states 
that it should be treated as ``direct evidence of potential adverse 
effects'' and ``data showing this response provide valuable information 
in assessing potential hazards posed by antiAChE pesticides'' (Id.). 
Unfortunately, useful data measuring AChE inhibition in the peripheral 
nervous system tissues has only been relatively rarely captured by 
standard toxicology testing, particularly for the NMC compounds. For 
central nervous system effects, however, more recent neurotoxicity 
studies ``have sought to characterize the time course of inhibition in 
* * * [the] brain, including brain regions, after acute and 90-day 
exposures'' (Id. at 27).
    AChE inhibition in the blood is one step further removed from the 
direct harmful consequences of AChE-inhibiting pesticides. According to 
the policy, inhibition of blood AChEs ``is not an adverse effect, but 
may indicate a potential for adverse effects on the nervous system'' 
(Id. at 28). The policy states that ``[a]s a matter of science policy, 
blood AChE data are considered appropriate surrogate measures of 
potential effects on peripheral nervous system AChE activity in 
animals, for central nervous system (``CNS'') AChE activity in animals 
when CNS data are lacking and for both peripheral and central nervous 
system AChE in humans'' (Id. at 29). The policy notes that ``there is 
often a direct relationship between a greater magnitude of exposure [to 
a AChE-inhibiting pesticide] and an increase in incidence and severity 
of clinical signs and symptoms as well as blood AChE inhibition'' (Id. 
at 30). Thus, the policy regards blood AChE data as ``appropriate 
endpoints for derivation of reference doses or concentrations when 
considered in a weight-of-the-evidence analysis of the entire database 
* * *'' (Id. at 29). Between AChE inhibition measured in red blood cell 
(``RBC'') or blood plasma, the policy states a preference for reliance 
on RBC AChE measurements because plasma is composed of a mixture of 
acetylcholinesterase and butyrylcholinesterase, and inhibition of the 
latter is less clearly tied to inhibition of acetylcholinesterase in 
the nervous system (Id. at 29, 32).
    EPA has relied on a benchmark dose (BMD) approach for deriving the 
PoD from the available rat toxicity studies. A BMD is a point estimate 
along a dose-response curve that corresponds to a specific response 
level. For example, a BMD10 represents a 10% change from the 
background; 10% is often used as a typical value for the response of 
concern (Ref. 76). Generically, the direction of change from background 
can be an increase or a decrease depending on the biological parameter 
and the chemical of interest. In the case of carbofuran, inhibition of 
AChE is the toxic effect of concern. Following exposure to carbofuran, 
the normal biological activity of the AChE enzyme is decreased (i.e., 
the enzyme is inhibited). Thus, when evaluating BMDs for carbofuran, 
the Agency is interested in a decrease in AChE activity compared to 
normal activity levels, which are also termed ``background'' levels. 
Measurements of ``background'' AChE activity levels are usually 
obtained from animals in experimental studies that are not treated with 
the pesticide of interest (i.e., ``negative control'' animals).
    In addition to the BMD, a confidence limit was also calculated. 
Confidence limits express the uncertainty in a BMD that may be due to 
sampling and/or

[[Page 59613]]

experimental error. The lower confidence limit on the dose used as the 
BMD is termed the BMDL, which the Agency uses as the PoD. Use of the 
BMDL for deriving the PoD rewards better experimental design and 
procedures that provide more precise estimates of the BMD, resulting in 
tighter confidence intervals. Use of the BMDL also helps ensure with 
high confidence (e.g., 95% confidence) that the selected percentage of 
AChE inhibition is not exceeded. From the PoD, EPA calculates the RfD 
and aPAD. Specific to carbofuran and the other NMCs, EPA the FIFRA SAP 
has reviewed and supported the statistical methods used to derive the 
BMD and BMDLs on multiple occasions (Refs. 34, 35, 36).
    In the Agency's BMD analysis for carbofuran, EPA used a response 
level of 10% brain AChE inhibition; this value represents the estimated 
dose where AChE is inhibited by 10%, compared to untreated animals. For 
the last several years EPA has used the 10% value to regulate AChE 
inhibiting pesticides, including organophosphorous pesticides (OPs) and 
NMCs. For a variety of toxicological and statistical reasons, EPA chose 
10% brain AChE inhibition as the response level for use in BMD 
calculations. EPA analyses have demonstrated that 10% is a level that 
can be reliably measured in the majority of rat toxicity studies; is 
generally at or near the limit of sensitivity for discerning a 
statistically significant decrease in AChE activity across the brain 
compartment; and is a response level close to the background (Refs. 34, 
35).

B. Estimating Human Dietary Exposure Levels

    Pursuant to section 408(b) of the FFDCA, EPA has evaluated 
carbofuran's dietary risks based on ``aggregate exposure'' to 
carbofuran. By ``aggregate exposure,'' EPA is referring to exposure to 
carbofuran by multiple pathways of exposure. EPA uses available data 
and standard analytical methods, together with assumptions designed to 
be protective of public health, to produce separate estimates of 
exposure for a highly exposed subgroup of the general population, for 
each potential pathway and route of exposure. For acute risks, EPA then 
calculates potential aggregate exposure and risk by using probabalistic 
\1\ techniques to combine distributions of potential exposures in the 
population for each route or pathway. For dietary analyses, the 
relevant sources of potential exposure to carbofuran are from the 
ingestion of residues in food and drinking water. The Agency uses a 
combination of monitoring data and predictive models to evaluate 
environmental exposure of humans to carbofuran.
---------------------------------------------------------------------------

    \1\ Probabilistic analysis is used to predict the frequency with 
which variations of a given event will occur. By taking into account 
the actual distribution of possible consumption and pesticide 
residue values, probabilistic analysis for pesticide exposure 
assessments ``provides more accurate information on the range and 
probability of possible exposure and their associated risk values'' 
(Ref. 77). In capsule, a probabilistic pesticide exposure analysis 
constructs a distribution of potential exposures based on data on 
consumption patterns and residue levels and provides a ranking of 
the probability that each potential exposure will occur. People 
consume differing amounts of the same foods, including none at all, 
and a food will contain differing amounts of a pesticide residue, 
including none at all.
---------------------------------------------------------------------------

    1. Exposure from Food. The level of human exposure to pesticide 
residues in food is a function of both the pesticide residues in food 
and the amount of food consumed. Data on the residues of carbofuran in 
foods are available from a variety of sources. One of the primary 
sources of data comes from federally-conducted surveys, including the 
Pesticide Data Program (PDP) conducted by the USDA. Further, market 
basket surveys, which are typically performed by registrants, can 
provide additional residue data. These data generally provide a 
characterization of pesticide residues in or on foods consumed by the 
U.S. population that closely approximates real world exposures because 
they are sampled closer to the point of consumption in the chain of 
commerce than field trial data, which are generated to establish the 
maximum level of legal residues that could result from maximum 
permissible use of the pesticide. In certain circumstances, when EPA 
believes the information will provide more accurate exposure estimates, 
EPA will rely on field trial data (see below in Unit VI.E.1).
    EPA relies on USDA's Continuing Survey of Food Intake by 
Individuals (CSFII) for information on food consumption by the US 
population as well as 32 subgroups based on age, gender, ethnicity, and 
region. The latest CSFII was conducted in 1994-1996 and 1998. The 1998 
survey was a special survey required by the FQPA to supplement the 
number of children survey participants. DEEM-FCID also contains 
``recipes'' that convert foods as consumed (e.g., pizza) back into 
their component raw agricultural commodities (e.g., wheat from flour, 
or tomatoes from sauce, etc.). This is necessary because residue data 
are generally gathered on raw agricultural commodities rather than on 
finished ready-to-eat food. Data on residue values for a particular 
pesticide and the RfD or PADs for that pesticide are inputs to the 
DEEM-FCID computer program to estimate exposure and risk.
    The DEEM-FCID computer program estimates exposure by combining data 
on human consumption amounts with residue values in food commodities. 
DEEM-FCID also compares exposure estimates to appropriate RfD or PAD 
values to estimate risk. EPA uses DEEM-FCID to estimate exposure for 
the general U.S. population as well as for 32 subgroups based on age, 
sex, ethnicity, and region. DEEM-FCID allows EPA to process extensive 
volumes of data on human consumption amounts and residue levels in 
making risk estimates. Matching consumption and residue data, as well 
as managing the thousands of repeated analyses of the consumption 
database conducted under probabilistic risk assessment techniques, 
requires the use of a computer.
    For carbofuran's assessment, EPA used DEEM-FCID to calculate risk 
estimates based on a probabilistic distribution. DEEM-FCID combines the 
full range of residue values for each food with the full range of data 
on individual consumption amounts to create a distribution of exposure 
and risk levels. More specifically, DEEM-FCID creates this distribution 
by calculating an exposure value for each reported day of consumption 
per person (``person/day'') in CSFII, assuming that all foods 
potentially bearing the pesticide residue contain such residue at a 
value selected randomly from the exposure data sets. The exposure 
amounts for the thousands of person/days in the CSFII are then 
collected in a frequency distribution. EPA also uses DEEM-FCID to 
compute a distribution taking into account both the full range of data 
on consumption levels and the full range of data on potential residue 
levels in food. Combining consumption and residue levels into a 
distribution of potential exposures and risk requires use of 
probabilistic techniques.
    The probabilistic technique that DEEM-FCID uses to combine 
differing levels of consumption and residues involves the following 
steps:
    (1) Identification of any food(s) that could bear the residue in 
question for each person/day in the CSFII;
    (2) Calculation of an exposure level for each of the thousands of 
person/days in the CSFII database, based on the foods identified in 
Step 1 by randomly selecting residue values for the foods from 
the residue database;
    (3) Repetition of Step 2 one thousand times for each 
person/day; and

[[Page 59614]]

    (4) Collection of all of the hundreds of thousands of potential 
exposures estimated in Steps 2 and 3 in a frequency 
distribution.
    The resulting probabilistic assessment presents a range of 
exposure/risk estimates.
    2. Exposure from water. EPA may use field monitoring data and/or 
simulation water exposure models to generate pesticide concentration 
estimates in drinking water. Monitoring and modeling are both important 
tools for estimating pesticide concentrations in water and can provide 
different types of information. Monitoring data can provide estimates 
of pesticide concentrations in water that are representative of the 
specific agricultural or residential pesticide practices in specific 
locations, under the environmental conditions associated with a 
sampling design (i.e., the locations of sampling, the times of the year 
samples were taken, and the frequency by which samples were collected). 
Although monitoring data can provide a direct measure of the 
concentration of a pesticide in water, it does not always provide a 
reliable basis for estimating spatial and temporal variability in 
exposures because sampling may not occur in areas with the highest 
pesticide use, and/or when the pesticides are being used and/or at an 
appropriate sampling frequency to detect high concentrations of a 
pesticide that occur over the period of a day to several days.
    Because of the limitations in most monitoring studies, EPA's 
standard approach is to use simulation water exposure models as the 
primary means to estimate pesticide exposure levels in drinking water. 
Modeling is a useful tool for characterizing vulnerable sites, and can 
be used to estimate peak pesticide water concentrations from 
infrequent, large rain events. EPA's computer models use detailed 
information on soil properties, crop characteristics, and weather 
patterns to estimate water concentrations in vulnerable locations where 
the pesticide could be used according to its label (69 FR 30042, 30058-
30065 (May 26, 2004)). These models calculate estimated water 
concentrations of pesticides using laboratory data that describe how 
fast the pesticide breaks down to other chemicals and how it moves in 
the environment at these vulnerable locations. The modeling provides an 
estimate of pesticide concentrations in ground and surface water. 
Depending on the modeling algorithm (e.g., surface water modeling 
scenarios), daily concentrations can be estimated continuously over 
long periods of time, and for places that are of most interest for any 
particular pesticide.
    EPA relies on models it has developed for estimating pesticide 
concentrations in both surface water and ground water. Typically EPA 
uses a two-tiered approach to modeling pesticide concentrations in 
surface and ground water. If the first tier model suggests that 
pesticide levels in water may be unacceptably high, a more refined 
model is used as a second tier assessment. The second tier model for 
surface water is actually a combination of two models: The Pesticide 
Root Zone Model (PRZM) and the Exposure Analysis Model System (EXAMS). 
The second tier model for ground water uses PRZM alone.
    A detailed description of the models routinely used for exposure 
assessment is available from the EPA OPP Water Models Web site: http://
www.epa.gov/oppefed1/models/water/index.htm. These models provide a 
means for EPA to estimate daily pesticide concentrations in surface 
water sources of drinking water (a reservoir) using local soil, site, 
hydrology, and weather characteristics along with pesticide application 
and agricultural management practices, and pesticide environmental fate 
and transport properties. Consistent with the recommendations of the 
FIFRA SAP, EPA also considers regional percent cropped area factors 
(PCA) which take into account the potential extent of cropped areas 
that could be treated with pesticides in a particular area. The PRZM 
and EXAMS models used by EPA were developed by EPA's Office of Research 
and Development (ORD), and are used by many international pesticide 
regulatory agencies to estimate pesticide exposure in surface water. 
EPA's use of the percent cropped area factors and the Index Reservoir 
scenario was reviewed and approved by the FIFRA SAP in 1999 and 1998, 
respectively (Refs. 30, 31).
    In modeling potential surface water concentrations, EPA attempts to 
model areas of the country that are vulnerable to surface water 
contamination rather than simply model ``typical'' concentrations 
occurring across the nation. Consequently, EPA models exposures 
occurring in small, highly agricultural watersheds in different growing 
areas throughout the country, over a 30-year period. The scenarios are 
designed to capture residue levels in drinking water from reservoirs 
with small watersheds with a large percentage of land use in 
agricultural production. EPA's models take into account that pesticide 
residues in water fluctuate daily, seasonally, and yearly as a result 
of the timing of pesticide applications, the vulnerability of the water 
supply to pesticide loading through runoff, spray drift and/or 
leaching, and changes in the weather. Concentrations are also affected 
by the method of application, the location and characteristics of the 
sites where a pesticide is used, the climate, and the type and degree 
of pest pressure.
    EPA uses the output of daily concentration values from tier two 
modeling as an input to DEEM-FCID, which combines water concentrations 
with drinking water consumption information in the daily diet to 
generate a distribution of exposures from consumption of drinking water 
contaminated with pesticides. These results are then used to calculate 
a probabilistic assessment of the aggregate human exposure and risk 
from residues in food and drinking water.
    3. Aggregate Exposure Analyses. Using probabilistic analyses, EPA 
combines the national food exposures with the exposures derived for 
individual region and crop-specific drinking water scenarios to derive 
estimates of aggregate exposure. Although food is distributed 
nationally, and exposures to pesticide residues are therefore not 
expected to vary substantially throughout the country, drinking water 
is locally derived and consumed and there can be significant variations 
in pesticide levels in local watersheds due to geographic, climatic, 
and other factors. To be protective of all population subgroups, EPA 
uses modeled estimates from vulnerable watersheds in calculating 
aggregate exposure.
    EPA's standard acute dietary exposure assessment calculates total 
dietary exposure over a 24-hour period; that is consumption over 24 
hours is summed and no account is taken of the fact that eating and 
drinking occasions may spread out exposures over a day. This total 
daily exposure generally provides reasonable estimates of the risks 
from acute dietary exposures, given the nature of most chemical 
endpoints. Due to the rapid recovery associated with carbofuran 
toxicity (AChE inhibition), 24-hour exposure periods may or may not be 
appropriate. To the extent that a day's eating or drinking occasions 
leading to high total daily exposure might be found close together in 
time, or to occur from a single eating event, minimal AChE recovery 
would occur between eating occasions (i.e., exposure events). In that 
case, the ``24-hour sum'' approach, which sums eating events over a 24-
hour period, would provide reasonable estimates of risk from food

[[Page 59615]]

and drinking water. Conversely, to the extent that eating occasions 
leading to high total daily exposures are widely separated in time 
(within one day) such that substantial AChE recovery occurs between 
eating occasions, then the estimated risks under any 24-hour sum 
approach may be overstated. In that case, a more sophisticated 
approach--one that accounts for intra-day eating and drinking patterns 
and the recovery of AChE between exposure events--may be more 
appropriate. This approach is referred to as the ``Eating Occasions 
Analysis'' and it takes into account the fact that the toxicological 
effect of a first dose may be reduced or tempered prior to a second (or 
subsequent) dose.
    Thus, rather than treating a full day's exposure as a one-time 
``bolus'' dose, as is typically done in the Agency's assessments, the 
Eating Occasion analysis uses the actual time of eating or drinking 
occasion, and amounts consumed as reported by individuals to the USDA 
CSFII. The actual CSFII-recorded time of each eating event is used to 
``separate out'' the exposures due to each eating occasion; in doing 
so, this ``separation'' allows the Agency to distinguish between each 
intake event and account for the fact that at least some partial 
recovery of AChE inhibition attributable to the first (earlier) 
exposure occurs before the second exposure event. For chemicals for 
which the toxic effect is rapidly reversible, the time between two (or 
more) exposure events permits partial to full recovery from the toxic 
effect from the first exposure and it is this ``partial recovery'' that 
is specifically accounted for by the Eating Occasion Analysis. More 
specifically, an estimated ``persisting dose'' from the first exposure 
event is added to the second exposure event to account for the partial 
recovery of AChE inhibition that occurs over the time between the first 
and second exposures. The `persisting dose' terminology, and this 
general approach were originally suggested by the FIFRA SAP in the 
context of assessing AChE inhibition from cumulative exposures to OP 
pesticides (Ref. 33).

C. Selection of Acute Dietary Exposure Level of Concern

    Because probabilistic assessments generally are based on a 
realistic range of residue values to which the population may be 
exposed, EPA's starting point for estimating exposure and risk for such 
aggregate assessments is the 99.9th percentile of the population under 
evaluation, which represents one person out of every 1000 persons. When 
using a probabilistic method of estimating acute dietary exposure, EPA 
typically assumes that, when the 99.9th percentile of acute exposure is 
equal to or less than the aPAD, the level of concern for acute risk has 
not been exceeded. By contrast, where the analysis indicates that 
estimated exposure at the 99.9th percentile exceeds the aPAD, EPA would 
generally conduct one or more sensitivity analyses to determine the 
extent to which the estimated exposures at the high-end percentiles may 
be affected by unusually high food consumption or residue values. To 
the extent that one or a few values seem to ``drive'' the exposure 
estimates at the high end of exposure, EPA would consider whether these 
values are reasonable and should be used as the primary basis for 
regulatory decision making (Ref. 77).

V. Carbofuran Background and Regulatory History

A. Tolerance Reassessment and Pesticide Reregistration

    In July 2006, EPA completed a refined acute probabilistic dietary 
risk assessment for carbofuran as part of the tolerance reassessment 
program under section 408(q) of the FFDCA and pesticide reregistration 
under section 4 of FIFRA. The assessment was conducted using Dietary 
Exposure Evaluation Model-Food Commodity Intake Database (DEEM-
FCIDTM, Version 200-2.02), which incorporates consumption 
data from the United States Department of Agriculture's (USDA's) 
Nationwide Continuing Surveys of Food Intake by Individuals (CSFII), 
1994-1996 and 1998, as well as carbofuran monitoring data from USDA's 
Pesticide Data Program \2\ (PDP), estimated percent crop treated 
information, and processing/cooking factors, where applicable. The 
assessment was conducted applying an additional 500-fold safety factor 
that included a 5X children's safety factor, pursuant to section 
408(b)(2)(C). That refined assessment showed acute dietary risks from 
carbofuran residues in food significantly above EPA's level of concern 
(Ref. 14). Based in part on the results of that assessment, EPA 
concluded that carbofuran failed to meet the revised safety standard in 
FFDCA section 408(b) and the standard for FIFRA reregistration.\3\
---------------------------------------------------------------------------

    \2\ USDA's Pesticide Data Program monitors for pesticides in 
certain foods at the distribution points just before release to 
supermarkets and grocery stores.
    \3\ Although not relevant to this proceeding, in addition to 
determining that use of carbofuran resulted in unacceptable dietary 
risks, EPA concluded that use of carbofuran did not meet the 
standard for FIFRA registration based on unacceptable occupational 
and ecological risks.
---------------------------------------------------------------------------

    The tolerance reassessment and FIFRA reregistration process for 
carbofuran contained numerous opportunities for public participation. 
These included public comment periods on the preliminary ecological 
risk assessment (June-August 2005), the preliminary human health risk 
assessment (September-November 2005), the revised combined risk 
assessment (March-May 2006), and the interim Registration Eligibility 
Document (RED) (August-November 2006). EPA received over 200 comments 
(plus a letter campaign supporting carbofuran with 2,896 signatories) 
to the 2006 RED. FMC submitted extensive comments throughout the 
process (including, but not limited to, a comment of 62 pages plus 13 
attachments totaling over 900 pages on August 23, 2005, a letter with 
20 attachments on November 11, 2005, 46 pages of comments on January 
26, 2006, 78 pages of comments on February 17, 2006, a 15-page letter 
with 8 attachments on May 22, 2006, over 200 pages on May 24, 2006, and 
other submissions. Following issuance of the RED in August 2006, FMC 
stated that they would be submitting new data to refute EPA's 
ecological and human health risk concerns, as well as EPA's benefits 
assessments. Twenty-three submissions with studies and analyses were 
submitted in 2007, all of which EPA reviewed. FMC submitted 175 pages 
of comments to the proposed tolerance revocations jointly with the NPC, 
NCGA, NCC, and NSA on 9/29/09. The Agency has also met numerous times 
with FMC, growers, and other stakeholders regarding carbofuran.
    One particular aspect of the risk assessment process that involved 
substantial public participation opportunities was EPA's review of the 
human toxicology studies performed with carbofuran. In making a 
determination on whether these studies met the standards of the Human 
Research rule, EPA, as required, sought the advice of the HSRB. The 
HSRB review process includes the opportunity for the public both to 
submit written comments and to make an oral presentation to the HSRB. 
FMC gave both written and oral comments at the HSRB meeting, which was 
held May 2-4, 2006. FMC also submitted written comments on the final 
HSRB report on the meeting.

[[Page 59616]]

B. Draft Notice of Intent to Cancel Carbofuran Registrations

    In January 2008, EPA published a draft Notice of Intent to Cancel 
(NOIC) all carbofuran registrations, based in part on carbofuran's 
dietary risks. As mandated by FIFRA, EPA solicited comments from the 
FIFRA Scientific Advisory Panel (SAP) on its draft NOIC.\4\ As part of 
that process, EPA presented its dietary risk assessment of carbofuran 
to the FIFRA SAP, and requested comment on key issues in the risk 
assessment: The Agency's approach to selecting the point of departure 
and the children's safety factor. FMC and the remaining Petitioners 
participated in this meeting, making substantial presentations to the 
SAP. As described in the proposal, the Agency believes that the Panel's 
responses unambiguously support the Agency's approach with regard to 
carbofuran's hazard identification and hazard characterization (73 FR 
44875 (July 31, 2008)). In addition, EPA believes that, on balance, the 
application of a 4X children's safety factor is consistent with the 
SAP's advice. Additional detail on the SAP's advice and EPA's responses 
can be found at Ref. 83.
---------------------------------------------------------------------------

    \4\ The draft NOIC was based on all of carbofuran's combined 
risks--dietary, occupational, and ecological. Because some non-food 
use registrations remain, EPA anticipates issuing the NOIC 
subsequent to undertaking the activities required to revoke the 
carbofuran tolerances to cancel these remaining uses.
---------------------------------------------------------------------------

C. Proposed Revocation of Carbofuran Tolerances

    Having considered the comments from the SAP, EPA initiated the 
process to revoke all carbofuran tolerances, publishing a proposed 
revocation on July 31, 2008 (73 FR 44,864 (July 31, 2008) (FRL-8378-
8)). EPA proposed to revoke all of the existing tolerances for residues 
of carbofuran on the grounds that aggregate exposure from all uses of 
carbofuran fails to meet the FFDCA section 408 safety standard (Id). 
Based on the contribution from food alone, EPA calculated dietary 
exposures to carbofuran exceed EPA's level of concern for all of the 
more sensitive subpopulations of infants and children. At the 99.9th 
percentile, aggregate carbofuran dietary exposure from food and 
drinking water from contaminated ground water was estimated to range 
from 1100% of the aPAD for adults, to greater than 10,000% of the aPAD 
for infants, the population subgroup with the highest estimated dietary 
exposure (Ref. 12). Similarly, aggregate dietary exposures from food 
and drinking water from surface water, based on contamination from use 
on corn in Nebraska, ranged from 340% of the aPAD for adults, to 3,900% 
aPAD for infants. EPA also determined that, based on actual residue 
levels measured in food in commerce, individual children consuming 
typical amounts of a single food item received unsafe levels of 
carbofuran. For example, based on the level of residues detected on in 
the food supply, a child between 3-5 years, who consumed \1/2\ cup of 
cantaloupe, would receive a dose ranging between 180% and 7,200% of the 
aPAD. Finally, the proposal discussed a number of sensitivity analyses 
the Agency had calculated in order to further characterize the 
potential risks to children. Every one of these sensitivity analyses 
determined that estimated exposures significantly exceeded EPA's level 
of concern for children.
    EPA held a 60-day comment period on the proposed revocation rule. 
In the proposed rule, EPA made clear that if any person had concerns 
with EPA's proposed revocation, those concerns must be raised during 
the comment period to be preserved. Specifically, EPA stated:

    In addition to submitting comments in response to this proposal, 
you may also submit an objection at the time of the final rule. If 
you anticipate that you may wish to file objections to the final 
rule, you must raise those issues in your comments on this proposal. 
EPA will treat as waived, any issue not originally raised in 
comments on this proposal. Similarly, if you fail to file an 
objection to the final rule within the time period specified, you 
will have waived the right to raise any issues resolved in the final 
rule. After the specified time, issues resolved in the final rule 
cannot be raised again in any subsequent proceedings on this rule.

(73 FR at 44865).

D. Petitioners' Comments on the Proposed Rule

    The comment period for the proposed rule closed on September 29, 
2008. During the comment period, the Petitioners submitted comments 
challenging particular aspects of EPA's risk assessment. For example, 
the Petitioners challenged the basis for EPA's 4X children's safety 
factor, and the method and assumptions on which EPA relied to estimate 
drinking water concentrations. In addition, the registrant, FMC 
Corporation, requested that EPA cancel the use on 22 of the crops on 
which it was registered, including many of the foods posing the highest 
risks to children. FMC also requested that EPA modify its labels to 
include a number of additional restrictions intended to mitigate the 
risks identified in EPA's risk assessment. For example, use was 
prohibited on much of the Eastern US to protect vulnerable sources of 
groundwater; use restrictions were imposed in other areas of the 
country, preventing use within set distances to prevent runoff into 
sources of surface water drinking water supplies.
    On November 7, 2008, the Petitioners submitted additional 
information as a supplement to their September comments. Specifically, 
they submitted carbofuran use data that the Petitioners used in 
preparing its surface water assessments. The information consisted of a 
spreadsheet that contained all of the data provided to the Water Panel 
by FMC, and a document that explained the materials, methods, and 
procedures employed by the Panel to utilize this data.
    On December 24, 2008, FMC submitted a petition requesting that EPA 
stay the effective date of the tolerance revocations, and that EPA 
consider additional information, including further risk mitigation 
measure that the registrant intended to implement, as well as 
additional analyses that the Petitioners' experts were developing.

E. Final Rule Revoking Carbofuran Tolerances

    On May 15, 2009, EPA published its final rule, based on a revised 
risk assessment that addressed the voluntary cancellations and label 
restrictions submitted by the close of the September 29 comment period. 
The only food uses that remained registered after the voluntary 
cancellations were sunflowers, corn, potatoes, and pumpkins. In 
response to the changes made on the labels, EPA revised its risk 
assessment to account for the reduced number of crops, the altered 
geographic restrictions, and the additional risk mitigation measures 
proposed as part of FMC's comments.
    Having considered all comments received by the close of the comment 
period, and based on its revised analyses, EPA concluded that aggregate 
exposures from all remaining uses of carbofuran were still unsafe for 
infants and children, and that revocation of the remaining tolerances 
was warranted. The final rule explained that, although the recent 
cancellation of several registered uses reduced the dietary risks to 
children, EPA's analyses still showed that estimated exposures 
significantly exceed EPA's level of concern for children. For example, 
EPA determined that the estimated risks could be as high as 9,400% of 
the aPAD for infants. A detailed description of the risk assessment 
supporting the final rule follows.

[[Page 59617]]

    1. Toxicity. AChE inhibition in brain and the PNS is the initial 
adverse biological event which results from exposure to carbofuran, and 
with sufficient levels of inhibition leads to other effects such as 
tremors, dizziness, as well as gastrointestinal and cardiovascular 
effects, including bradycardia (Ref. 15). Thus, AChE inhibition 
provides the most appropriate effect to use in risk extrapolation for 
derivation of RfDs and PADs. Protecting against AChE inhibition ensures 
that the other adverse effects associated with cholinergic toxicity, 
mentioned above, do not occur.
    There are three studies available that compare the effects of 
carbofuran on eleven-day-old rats (i.e., post-natal day 11 or PND11) 
rats with those in young adult rats (herein called comparative AChE 
studies) (Refs. 1, 2, 4, and 66). Two of these studies were submitted 
by FMC, the registrant, and one was performed by EPA-ORD. An additional 
study conducted by EPA-ORD involved PND17 rats (Ref. 63). Although it 
is not possible to directly correlate ages of juvenile rats to humans, 
PND11 rats are believed to be close in development to newborn humans. 
PND17 rats are believed to be closer developmentally to human toddlers 
(Refs. 10, 22, and 23). Other studies in adult rats used in the 
Agency's analysis included additional data from EPA-ORD (Refs. 54, 62, 
and 66).
    The studies in juvenile rats show a consistent pattern that 
juvenile rats are more sensitive than adult rats to the effects of 
carbofuran. These effects include inhibition in AChE in addition to 
incidence of clinical signs of neurotoxicity such as tremors. This 
pattern has also been observed for other NMC pesticides, which exhibit 
the same mechanism of toxicity as carbofuran (Ref. 81). It is not 
unusual for juvenile rats, or indeed, for infants or young children, to 
be more sensitive to chemical exposures as metabolic detoxification 
processes in the young are still developing. Because juvenile rats, 
called `pups' herein, are more sensitive than adult rats, data from 
pups provide the most relevant information for evaluating risk to 
infants and young children and are thus used to derive the PoD. In 
addition, typically (and this is the case for carbofuran) young 
children (ages 0-5 years) tend to be the age groups most exposed to 
carbofuran because they tend to ingest larger amounts of food and water 
per their body weight than do teenagers or adults. As such, the focus 
of EPA's analysis of carbofuran's dietary risk from residues in food 
and water is on young children (ages 0 to 5 years). Since these age 
groups experience the highest levels of dietary risk, protecting these 
groups against the effects of carbofuran will, in turn, also protect 
other age groups.
    The Agency used a meta-analysis to calculate the BMD10 
and BMDL10 for pups and adults; this analysis includes brain 
data from studies where either adult or juvenile rats or both were 
exposed to a single oral dose of carbofuran. The Agency used a dose-
time-response exponential model where benchmark dose and half-life to 
recovery can be estimated together. This model and the statistical 
approach to deriving the BMD10 s, BMDL10 s, and 
half-life to recovery have been reviewed and supported by the FIFRA SAP 
(Refs. 34, 35, and 36). The meta-analysis approach offers the advantage 
over using single studies by combining information across multiple 
studies and thus provides a robust PoD.
    For AChE-inhibiting pesticides, EPA generally evaluates the effects 
of the pesticide on both brain and RBC AChE. RBC AChE is used as a 
surrogate for effects on the PNS because data directly measuring 
effects on the PNS are difficult to obtain.
    Using quality brain AChE data from the three studies (two FMC, one 
EPA-ORD) conducted with PND11 rats, in combination, provides data to 
describe both low and high doses. By combining the three studies in 
PND11 animals together in a meta-analysis, the entire dose-response 
range is covered. The results of the BMD analysis for PND11 pup brain 
AChE data provide a BMD10 of 0.04 mg/kg/day and 
BMDL10 of 0.03 mg/kg/day--this BMDL10 of 0.03 mg/
kg/day provides the PoD (Ref. 70).
    EPA, however, lacked adequate data on carbofuran's effects on RBC 
AChE. Two studies required from FMC were rejected as flawed. To account 
for the lack of data in the PNS and/or a surrogate (i.e., RBC AChE 
inhibition data) in pups at the low end of the response curve, and for 
the fact that RBC AChE inhibition appears to be a more sensitive point 
of departure compared to brain AChE inhibition, EPA determined that, 
consistent with the statutory mandate, some portion of the statutory 
default 10X children's safety factor needed to be retained. Because 
there are some carbofuran data that characterize the toxicity in 
juveniles, EPA concluded that the weight-of-the-evidence supports 
reducing the statutory factor of 10X to a value lower than 10X. This 
results in a children's safety factor that is less than 10 but more 
than 1.
    The modified children's safety factor takes into account the 
greater sensitivity of the RBC AChE. The preferred approach to 
comparing the relative sensitivity of brain and RBC AChE inhibition 
would be to compare the BMD10 estimates. However, 
BMD10 estimates from the available RBC AChE inhibition data 
are not reliable due to lack of data at the low end of the dose 
response curve. As an alternative approach, EPA used the ratio of brain 
to RBC AChE inhibition at the BMD50, since there are quality 
data at or near the 50% response level such that a reliable estimate 
can be calculated. EPA estimated the RBC BMD50 to brain 
BMD50 potency ratio using EPA's data for RBC (the only 
reliable RBC data in PND11 animals for carbofuran) and all available 
data in PND11 animals for brain. There is, however, an assumption 
associated with using the 50% response level--namely that the magnitude 
of difference between RBC and brain AChE inhibition is constant across 
dose. In other words, EPA is assuming the RBC and brain AChE dose 
response curves are parallel. There are currently no data to test this 
assumption for carbofuran.
    Comparing RBC BMD50 and brain BMD50 AChE 
inhibition, EPA calculated a BMD50 ratio of 4.1X. 
Accordingly, EPA concluded that a children's safety factor of 4X would 
be protective of infants and children.
    Using the BMDL10 of 0.03 mg/kg/day, combined with the 
default 10X interspecies and intraspecies factors, along with the 4X 
children's safety factor results in an aPAD = 0.000075 mg/kg/day for 
infants and children. The aPAD for youths and adults is calculated in 
the same manner, but EPA does not apply the 4X children's safety 
factor, resulting in an aPAD of 0.0002 mg/kg/day.
    2. Acute Exposures from Food. The estimated acute dietary exposure 
from carbofuran residues in food alone (i.e., assuming no additional 
carbofuran exposure from drinking water), is below EPA's level of 
concern for the U.S. Population and all population subgroups. Children 
1 to 2 years of age (78% aPAD) were the most highly exposed population 
subgroup when food only was included. The major driver of the acute 
dietary exposure risk (food only) for Children 1 to 2 years is milk, at 
greater than 90% of the exposure.
    3. Acute Exposures from Drinking Water. EPA's analyses show that 
those individuals-both adults as well as children--who receive their 
drinking water from vulnerable sources are exposed to levels that 
exceed EPA's level of concern--in some cases by orders of magnitude. 
This primarily includes those populations consuming drinking water from 
ground water from

[[Page 59618]]

shallow wells in acidic aquifers overlaid with sandy soils that have 
had crops treated with carbofuran. It could also include those 
populations that obtain their drinking water from reservoirs located in 
small agricultural watersheds, prone to runoff, and predominated by 
crops that are treated with carbofuran, although there is more 
uncertainty associated with these exposure estimates.
    a. Ground Water. In EPA's revised assessment, ground water 
concentrations were estimated for all remaining crops on carbofuran 
labels, and used two new Tier 2 scenarios. Based on a new corn 
scenario, representative of potentially vulnerable areas in the upper 
Midwest, EPA estimated 1-in-10-year concentrations for ground water 
source drinking water of 16 to 1.6 x 10-3 [mu]g/L, for pH 
6.5 and 7, respectively. A potato scenario representing use in the 
Northwest estimated no measurable concentrations of carbofuran in 
ground water. Other remaining uses were modeled using a Tier 1 ground 
water model (Screening Concentration in Groundwater) with estimated 
peak 90-day concentrations of 48-178 [mu]g/L, depending on application 
rate. Well setback prohibitions of 50 feet were proposed on the 
September 2008 label for the flowable and granular formulations in 
select counties in Kentucky (seven counties), Louisiana (one county), 
Minnesota (one county), and Tennessee (one county). Analysis of the 
impact of these setbacks for the use on corn indicated that the 
setbacks would not reduce concentrations significantly at locations 
where exposure to carbofuran in ground water is of concern because at 
acid pHs, carbofuran does not degrade sufficiently during the travel 
time from the application site to the well to substantially reduce the 
concentration.
    Exposure estimates for this assessment are drawn primarily from 
EPA's modeling. To conduct its modeling, EPA examined readily available 
data with respect to ground water and soil pH to evaluate the spatial 
variability of pH. Ground water pH values can span a wide range; this 
is especially true for shallow ground water systems, where local 
conditions can greatly affect the quality and characteristics of the 
water (higher or lower pHs compared to average values). The ground 
water simulations reflect variability in pH by modeling carbofuran 
leaching in four different pH conditions (pH 5.25, 6.5, 7.0, and 8.7), 
representing the range in the Wisconsin aquifer system. The upper and 
lower bound of pH values that EPA chose for this assessment were 
measured values from the aquifer, and the remaining two values were 
chosen to reflect common pH values between the measured values. Based 
on EPA's assessment, the maximum 1-in-10-year peak carbofuran 
concentrations in vulnerable ground water for a single application on 
corn in Wisconsin, at a rate of 1 pound per acre were estimated to 
range from a low of less than 1 ppb based on a pH of 7 or higher, to a 
high of 16 ppb, based on a pH of 6.5.
    The results of EPA's revised corn modeling, based on a scenario in 
Wisconsin, are consistent with the results of the PGW study developed 
by FMC in Maryland in the early 1980s. Using higher use rates than 
currently permitted, the peak concentration measured in the PGW study 
was 65 ppb; when scaled to current use rates, the estimated peak 
concentration was 11 ppb. EPA's modeling is also consistent with a 
number of other targeted ground water studies conducted in the 1980s 
showing that high concentrations of carbofuran can occur in vulnerable 
areas; the results of these studies as well as the PGW study are 
summarized in References 13 and 67.
    While there have been additional ground water monitoring studies 
that included carbofuran as an analyte since that time, there has been 
no additional monitoring targeted to carbofuran use in areas where 
aquifers are vulnerable. However, data compiled in 2002 by EPA's Office 
of Water show that carbofuran was detected in treated drinking water at 
a few locations. Based on samples collected from 12,531 ground water 
supplies in 16 states, carbofuran was found at one public ground water 
system at a concentration of greater than 7 ppb and in two ground water 
systems at concentrations greater than 4 ppb (measurements below this 
limit were not reported). An infant receiving these concentrations 
would receive doses equivalent to 220% of the aPAD or 130% aPAD, 
respectively, based on a single 8 ounce serving of water. As this 
monitoring was not targeted to carbofuran, the likelihood is low that 
these samples capture peak concentrations. Given the lack of targeted 
monitoring, EPA has primarily relied on modeling to develop estimates 
of carbofuran residues in ground water sources of drinking water.
    EPA compiled a distribution of estimated carbofuran concentrations 
in water based on these estimates, which was used to generate 
probabilistic assessments of the potential exposures from drinking 
water derived from vulnerable ground water sources. Based on these 
assessments, estimated exposures ranged between 770% aPAD for adults to 
9400% aPAD for infants.
    b. Surface Water. For the final rule, EPA conducted additional 
refined modeling based on the September 2008 label submitted by FMC. 
The modeling addressed all of the domestic uses that remain registered, 
and included certain refinements to better understand the impacts of 
varying pH. EPA also conducted modeling to assess the impact of the 
proposed spray drift buffer requirements and other spray drift measures 
included on the September label.
    EPA estimated carbofuran concentrations resulting from the use on 
pumpkins by adjusting the estimated drinking water concentrations 
(EDWC) from a previous run simulating melons in Missouri; adjustments 
accounted for differences in application rate and row spacing. Two 
EDWCs were calculated for pumpkins: One based on a 36-inch row spacing, 
representing pumpkins for consumption (77.6 ppb); and a second based on 
a 60-inch row spacing, representing decorative pumpkins (46.6 ppb).
    EPA had previously evaluated the corn rootworm rescue treatment at 
seven representative sites, representing use in states with extensive 
carbofuran usage at locations more vulnerable than most in each state 
in areas corn is grown. Using measured rainfall values, and assuming 
typical rather than maximum use rates, peak concentrations for the corn 
rescue treatments simulated for Illinois, Iowa, Indiana, Kansas, 
Minnesota, Nebraska, and Texas ranged from 16.6-36.7 ppb (Ref. 47). 
Under the revised assessment to account for the September 2008 use 
restrictions, concentrations for corn, calculated including the 
proposed spray drift buffers in Kansas and Texas, decreased 5.1% and 
4.7%, respectively, from simulations with no buffer from the previous 
assessment (Ref. 47). In Kansas, the 1-in-10-year peak EDWCs decreased 
from 33.5 to 31.8 ppb when a 300-foot buffer was added, and in Texas, 
from 29.9 to 28.5 ppb with the addition of a 66-foot buffer.
    For the sunflower use, 12 simulations were performed for 
sunflowers, 9 in Kansas, and 3 in North Dakota. The North Dakota 
scenario was used to represent locations where sunflowers are grown 
that are vulnerable to pesticide movement to surface water while the 
Kansas scenario represents places that are not particularly vulnerable, 
based on the limited rainfall and generally well-drained soils 
(hydrologic group B soils) that are found in that area. Estimated 1-in-
10-year concentrations ranged from 11.6 to 32.7

[[Page 59619]]

[mu]g/L. When simulating three applications, one at plant and two 
foliar with a 14-day interval between the two foliar applications and a 
66-foot buffer, the 1-in-10-year peak EDWC for North Dakota was 22.4 
[mu]g/L. In contrast, the same three applications in Kansas with a 14-
day interval between the foliar applications and a 300-foot buffer 
produced a 1-in-10-year peak EDWC of 20.5 [mu]g/L. The 1-in-10-year 
peak EDWCs, assuming that carbofuran is applied only at plant, were 
14.0 and 16.0 [mu]g/L in Kansas and North Dakota respectively. EPA also 
evaluated the impact of pH on carbofuran concentrations for sunflowers, 
resulting in a 10% decrease in 1-in-10-year peak concentrations 
assuming high pH in the reservoir. Spray drift buffers of 66 and 300 
feet decreased concentrations 4.7 and 5.1% for corn and 10.0% and 16.0% 
for sunflowers, respectively, in comparison to previous labels that had 
no spray drift buffer requirements. Additional details on these 
assessments can be found at Reference 84.
    These predicted carbofuran water concentrations are similar or 
lower than the peak concentrations reported in the United States 
Geological Survey-National Ambient Water Quality Survey (USGS-NAWQA) 
monitoring data. In addition, these data, which represent 
concentrations in surface water prior to any treatment by a public 
drinking water system, are consistent with the results of the 2002 data 
on finished water compiled by EPA's Office of Water. Based on samples 
collected from 1,394 surface water source drinking water supplies in 16 
states, carbofuran was found at no public drinking water supply systems 
at concentrations exceeding maximum contaminant level (MCL) of 40 ppb. 
However, carbofuran was found at one surface water public water system 
in finished (i.e., post-treatment) water at concentrations greater than 
4 ppb (measurements below this limit were not reported). Sampling is 
costly and is conducted typically four times a year or less at any 
single drinking water facility. The overall likelihood of collecting 
samples that capture peak exposure events is, therefore, low. For 
chemicals with acute risks of concern, such as carbofuran, higher 
concentrations and resulting risk is primarily associated with these 
peak events, which are not likely to be captured in monitoring unless 
the sampling rate is very high.
    There are few surface water field-scale studies targeted to 
carbofuran use that could be compared with modeling results. Most of 
these studies were conducted in fields that contain tile drains, which 
is a common practice throughout midwestern states to increase drainage 
in agricultural fields (Ref. 13). Drains are common in the upper 
Mississippi river basin (Illinois, Iowa, and the southern part of 
Minnesota), and the northern part of the Ohio River Basin (Indiana, 
Ohio, and Michigan) (Ref. 58). Although it is not possible to directly 
correlate the concentrations found in most of the studies with drinking 
water concentrations, these studies confirm that carbofuran use under 
such circumstances can contaminate surface water, as tile drains have 
been identified as a conduit to transport water and contaminants from 
the field to surface waters.
    EPA conducted dietary exposure analyses based on the modeling 
scenarios for the proposed September 2008 label. Exposures from all 
modeled scenarios substantially exceeded EPA's level of concern (Ref. 
12). For example, a Kansas sunflower scenario, assuming two foliar 
applications at a typical 1 lb active ingredient (a.i.) per acre use 
rate, applied at 14-day intervals, estimated a 1-in-10-year peak 
carbofuran water concentration of 11.6 ppb. Exposures at the 99.9th 
percentile based on this modeled distribution ranged from 160% of the 
aPAD for youths 13 to 19 years, to greater than 2,000% of the aPAD for 
infants. This scenario is intended to be representative of sites that 
are less vulnerable than most on which sunflowers could be grown. By 
contrast, exposure estimates from a comparable North Dakota sunflower 
scenario, intended to represent more vulnerable sites, estimated a 1-
in-10-year peak concentration of 22.4 ppb. These concentrations would 
result in estimated exposures ranging between 450% aPAD for youths 13 
to 19 years, to 5,500% aPAD for infants. Similarly, exposures based on 
a Washington surface water potato scenario, and using a 3 lb a.i. acre 
rate, ranged from 230% of the aPAD for children 6 to 12 years to 890% 
of the aPAD for infants, with a 1-in-10-year peak carbofuran 
concentration of 7.2 ppb. Although other crop scenarios resulted in 
higher exposures, estimates for these two crops are presented here, as 
they are major crops on which a large percentage of carbofuran use 
occurs. For example, one of EPA's refined exposure analyses is based on 
a Nebraska corn rootworm ``rescue treatment'' scenario, and assumes a 
single aerial application at a typical rate of 1 lb a.i. per acre. The 
full distribution of daily concentrations over a 30-year period was 
used in the probabilistic dietary risk assessment. The 1-in-10-year 
peak concentration of the distribution of values for the Nebraska corn 
rescue treatment was 22.3 ppb. Estimated dietary exposures based on 
these concentrations ratned from 340% of the aPAD for adults to 3900% 
of the aPAD for infants. More details on these assessments, as well as 
the assessments EPA conducted for other crop scenarios, can be found in 
References 12, 47, and 67.
    4. Aggregate (food and water) Exposures. EPA conducted a number of 
probabilistic analyses to combine the national food exposures with the 
exposures from the individual region and crop-specific drinking water 
scenarios. Although food is distributed nationally, and residue values 
are therefore not expected to vary substantially throughout the 
country, drinking water is locally derived and consumed and 
concentrations of pesticides in source water fluctuate over time and 
location for a variety of reasons. Consequently, EPA conducted several 
estimates of aggregate dietary risks by combining exposures from food 
and drinking water. These estimates showed that, because drinking water 
exposures from any of the crops on the label exceed safe levels, 
aggregate exposures from food and water are unsafe. Although EPA's 
assessments showed that, based on the Idaho potato scenarios, exposures 
from ground water from use on potatoes would be safe, surface water 
exposures from carbofuran use on potatoes far exceed the safety 
standard. More details on the individual aggregate assessments 
presented below, as well as the assessments EPA conducted for other 
regional and crop scenarios, can be found in References 12 and 13.
    The results of aggregate exposures from food and from drinking 
water derived from ground water in extremely vulnerable areas (i.e., 
from shallow wells associated with sandy soils and acidic aquifers, 
such as are found in Wisconsin), ranged from 780% of the aPAD for 
adults, to 9,400% of the aPAD for infants.
    The results of aggregate exposure from food and water derived from 
one of the least conservative surface water scenarios--Kansas 
sunflower, with two foliar applications--ranged from 190% of the aPAD 
for adults to 2,100% aPAD for infants. These estimates reflect the 
risks only for those people in watersheds with characteristics similar 
to that used in the scenario, and assuming that water treatment does 
not remove carbofuran. The estimated water concentrations are 
comparable to the maximum peak concentrations reported in monitoring 
studies that were not designed to detect peak, daily

[[Page 59620]]

concentrations of carbofuran in vulnerable locations.
    More details on this assessment, as well as the assessments EPA 
conducted for other crop scenarios, can be found in References 12, 47, 
and 67. For example, in the proposed rule, EPA presented the results 
from aggregate exposures resulting from a Nebraska surface water 
scenario based on a Nebraska corn rootworm ``rescue treatment.'' 
Estimated exposures from that scenario ranged from 330% of the aPAD for 
youths 13 to 19 years to 3,900% of the aPAD for infants.
    As noted previously, EPA's food and water exposure assessments 
typically sum exposures over a 24-hour period, and EPA used this 24-
hour total in developing its acute dietary risk assessment for 
carbofuran. Because of the rapid nature of carbofuran toxicity and 
recovery, EPA conducted an analysis using information about dietary 
exposure, timing of exposure within a day, and half-life of AChE 
inhibition from rats to estimate risk to carbofuran at durations less 
than 24 hours. Specifically, EPA has evaluated individual eating and 
drinking occasions and used the AChE half-life to recovery information 
(herein called half-life information) to estimate the residual effects 
from carbofuran from previous exposures within the day. The carbofuran 
analyses are described in the 2009 aggregate (dietary) memo (Ref. 55).
    Using the two FMC time course studies in rat pups, EPA calculated 
half-lives for recovery of 186 and 426 minutes (Refs. 24 and 25). The 
two values provide an indication that half-lives to recovery can vary 
among juvenile rats. By extension, children are expected to vary in 
their ability to recover from AChE inhibition where longer recoveries 
would be associated with a potentially higher ``persisting dose'' (as 
described below).
    This analysis had little impact on the exposures from food alone. 
However, accounting for drinking water consumption throughout the day 
and using the half-life to recovery information, risk is reduced by 
approximately 2-3X. Consequently, risk estimates for which food and 
drinking water are jointly considered and incorporated (i.e., Food + 
Drinking Water) are also reduced considerably--by a factor of two or 
more in some cases--compared to baseline. But even though the risk 
estimates from aggregate exposure are reduced, they nonetheless still 
substantially exceed EPA's level of concern for infants and children. 
Using drinking water derived from the surface water from the Idaho 
potato surface water scenario, which estimated one of the lowest 
exposure distributions, aggregate exposures at the 99.9th percentile 
ranged from 328% of the aPAD under the scenario for which infants 
rapidly metabolize carbofuran (e.g., 186 minute half-life), to a high 
of 473% of the aPAD under the scenario for which infants metabolize 
carbofuran more slowly, (e.g., scenarios in which a 426 minute half 
life is assumed).
    Moreover, even accounting for the estimated decreased risk from 
accounting for carbofuran's rapid reversibility, the Agency remains 
concerned about the risks from single eating or drinking events, as 
illustrated in the following example, based on an actual food 
consumption diary from the CSFII survey. A 4-month old male non-nursing 
infant weighing 10 kg is reported to have consumed a total of 1,070 
milliters (ml) of indirect water over eight different occasions during 
the day. The first eating occasion occurred at 6:30 a.m., when this 4 
month old consumed 8 fluid ounces of formula prepared from powder. The 
FCID food recipes indicate that this particular food item consists of 
approximately 87.7% water, and therefore, 8 ounces of formula contains 
approximately 214 ml (or grams) of indirect water; with the powder 
(various nutrients, dairy, soy, oils, etc.) accounting for the 
remaining 12.3%. This infant also reportedly consumed a full 8-ounce 
bottle of formula at 12 p.m., 4 p.m., and 8 p.m. that day. The food 
diary also indicates that the infant consumed about 1 tablespoon of 
water (14.8 ml) added to prepare rice cereal at 10 a.m., about 2 ounces 
of water (59.3 ml) added to pear juice at 11 a.m., another \1/2\ tsp of 
water (2.5 ml) to prepare more rice cereal at 8:30 p.m.; and finally, 
he consumed another 4 ounces of formula (107 ml) at 9:30 p.m.
    The infant's total daily water intake (1,070 ml, or approximately 
107 ml/kg/day) is not overly conservative, and represents substantially 
less than the 90th percentile value from CSFII on a ml water/kg 
bodyweight (ml/kg/bw) basis. As noted, carbofuran has been detected in 
finished water at concentrations of 4 ppb. For this 10 kg body weight 
infant, an 8-ounce bottle of formula prepared from water containing 
carbofuran at 4 ppb leads to drinking water exposures of 0.0856 
micrograms of active ingredient/kilogram of bodyweight ([micro]g ai/kg 
bw), or 114% of the aPAD. Based on the total daily water intake of 
1,070 ml/day (no reversibility), total daily exposures from water at 4 
ppb concentration would amount to 0.4158 [micro]g ai/kg bw, or 555% of 
the aPAD; this is the amount that would be used for this person-day in 
the Total Daily Approach.
    Peak inhibition occurs following each occasion on which the infant 
consumed 8 fluid ounces of formula (6 a.m., 12 p.m., 4 p.m. and 8 
p.m.); however, the maximum persisting dose occurs following the 9:30 
p.m. eating occasion, based on a 186-minute half-life parameter. This 
produces a maximum persisting dose of 0.1457 [micro]g ai/kg bw, or 
about 30% of the total daily exposure of 0.4158 [micro]g ai/kg bw 
derived above, or expressed as a fraction of the level of concern, the 
maximum persisting dose amounts to about 194% of the aPAD (or 30% of 
554%). Note that with drinking water concentration at 4 ppb, an infant 
consuming one 8 oz bottle of formula--prepared from powder and tap 
water containing carbofuran at 4 ppb will obtain exposures of 
approximately 114% of aPAD. Since many infants consume the equivalent 
of this amount on a single eating occasion, accounting for 
reversibility over multiple occasions is not essential to ascertain 
that infants quite likely have obtained drinking water exposures to 
carbofuran exceeding the level of concern based on drinking water 
concentrations found in public drinking water supplies.
    In this regard, it is important to note EPA's Eating Occasion 
Analyses underestimate exposures to the extent that they do not take 
into account carry-over effects from previous days, and because 
drinking water pesticide concentrations are randomly picked from the 
entire 30-year distribution. As discussed previously, DEEM-FCID 
[FN(TM)] is a single day dietary exposure model, and the DEEM-based 
Eating Occasion Analysis accounts for reversibility within each 
simulated person-day. All of the empirical data regarding time and 
amounts consumed (and corresponding exposures based on the 
corresponding residues) from the CSFII survey are used, along with the 
half-life to assess an equivalent persisting dose that produced the 
peak inhibition expected over the course of that day. This is a 
reasonable assumption for food alone; since the time between exposure 
events across 2 days is relatively high (compared to the half-life)--
most children (>9 months) tend to sleep through the night--and the time 
between dinner and breakfast the following morning is long enough it is 
reasonable to ``ignore'' persisting effects from the previous day. A 
single day exposure model will underestimate the persisting effects 
from drinking water exposures (formula) among infants, and newborns in 
particular (<3 months), since newborns tend to wake up every 2 to 4 
hours to feed. Any carry over

[[Page 59621]]

effects may be important, especially if exposures from the previous day 
are relatively high, since the time between the last feeding (formula) 
of the day and the first feeding of the subsequent day is short. A 
single day model also does not account for the effect of seasonal 
variations in drinking water concentrations, which will make this 
effect more pronounced during the high use season (i.e., the time of 
year when drinking water concentrations are high). Based on these 
analyses, the Agency concludes that the current exposure assessment 
methods used in the carbofuran dietary assessment provide realistic and 
high confidence estimates of risk to carbofuran exposure through food 
and water.

F. Response to FMC Comments on the Final Rule

    FMC's comments raised a range of issues. Those issues are not 
summarized here because FMC basically refilled many of its comments as 
objections without modifying them in response to EPA's decision in the 
final rule. In addition, FMA submitted a an alternate risk analysis 
purporting to show that aggregate carbofuran exposures to children 
would be safe. However, FMC failed to provide the data and details of 
that assessment to the Agency. They also failed to provide several 
critical components that served to support key inputs into that 
assessment; and for several of these, EPA was unable to replicate the 
claimed results based on the information contained in the comments. In 
the absence of such critical components, the Agency was unable to 
accept the validity or utility of the analyses, let alone rely on the 
results.
    Nonetheless, based on the summary descriptions provided in the 
registrant's comments, EPA concluded that the risk analyses contained a 
critical flaw. The commenters' determination of safety rests on the 
presumption that under real world conditions, events will always occur 
exactly as hypothesized by the multiple assumptions in their 
assessment. For example, the comments assumed, despite all available 
evidence to the contrary, that children would not be appreciably more 
sensitive to carbofuran's effects than adults. They assumed that 
carbofuran's effects will be highly reversible, and that children will 
be uniformly sensitive, such that the effects will be adequately 
accounted for by the assumption of a 150-minute half-life, despite the 
fact that children are not uniformly sensitive. They further assumed 
that there would be no carry over effect from the preceding day's 
exposures for infants. They assumed that the cancellation of use on 
alfalfa would reduce carbofuran residues in milk by over 70%, even 
though many cows' diet consists primarily of corn. They assumed that 
residues would decrease between 19% and 23% as a result of the buffer 
requirements on the September 2008 label, even though the label does 
not require the use of all of the recommended ``best management 
practices'' (e.g., no requirements regarding swath displacement), and 
applicators do not universally use such practices in the absence of any 
requirement. They assumed that average ground water pH adequately 
characterizes the temporal and spatial heterogeneity common in most 
areas, despite the available evidence to the contrary. Finally, they 
assumed that the percent of the crop treated in any watershed would 
never exceed 5%, despite varying pest pressures, consultant 
recommendations, and individual grower decisions. Leaving aside that 
EPA believes most, if not all of these assumptions are not supported by 
the available evidence described throughout the final rule, the 
probability of all these assumptions always simultaneously holding true 
under real world conditions is unreasonably low, and certainly does not 
approach the degree of certainty necessary for EPA to conclude that 
children's exposures will be safe.
    Determining whether residues will be safe for U.S. children is not 
a theoretical paper exercise; it cannot suffice to hypothesize a unique 
set of circumstances that make residues ``fit in the box.'' There must 
be a reasonable certainty that under the variability that exists under 
real world conditions, exposures will be ``safe.'' EPA's assessments 
incorporate a certain degree of conservatism precisely to account for 
the fact that assumptions must be made that may not prove accurate. 
This consideration is highly relevant for carbofuran, because as 
refined as EPA's assessments are, areas of uncertainty remain with 
regard to carbofuran's risk potential. For example, a recent 
epidemiological study reported that 45% of maternal and cord blood 
samples in a cohort of New York City residents of Northern Manhattan 
and the South Bronx between 2000 and 2004, contained low, but 
measurable residues of carbofuran (Ref. 88). The Agency is currently 
unable to account for the source of such sustained exposures at this 
frequency.
    A further consideration is that the risks of concern are acute 
risks to children. For acute risks, the higher values in a 
probabilistic risk assessment are often driven by relatively high 
values in a few exposures rather than relatively lower values in a 
greater number of exposures. This is due to the fact that an acute 
assessment looks at a narrow window of exposure where there are 
unlikely to be a great variety of consumption sources. Thus, to the 
extent that there is a high exposure it will be more likely due to a 
high residue value in a single consumption event. Additionally 
worrisome in this regard is that carbofuran is a highly potent (i.e., 
has a very steep dose-response curve), acute toxicant, and therefore 
any aPAD exceedances are more likely to have greater significance in 
terms of the potential likelihood of actual harm. For all of these 
reasons, EPA determined that the existing carbofuran tolerances did not 
meet the FFDCA safety standard, and should therefore be revoked.

VI. Response to Objections and Requests for Hearing

A. Overview

    Petitioners raised several objections that correspond to four basic 
categories of issues. The first category of objections and hearing 
requests relates to challenges to EPA's selection of the appropriate 
children's safety factor. In this category of issues, they raise 
primarily two claims: (1) That EPA's scientific basis for retaining a 
4X safety factor is flawed, and (2) the statistical calculations 
supporting the 4X safety factor are flawed, and based on faulty 
assumptions. The second category of issues relate to the manner in 
which EPA conducted its assessment of the exposure from carbofuran 
through drinking water sources. In this regard, all of their objections 
fall within three basic categories of issues: (1) EPA should have 
accounted for a more realistic percent of the crop treated (PCT) in its 
surface water modeling; (2) EPA's ground water concentration estimates 
are not based on the best available data, but on obsolete data and 
overly conservative assumptions; and (3) FMC's new label restrictions 
and revised terms of registration will ensure that drinking water 
concentrations will not exceed 1.1 ppb. The third category of issues 
relates to the manner in which EPA conducted its dietary risk 
assessment. Under this category, the objections and hearing requests 
raise four primary issues: (1) Petitioners challenge the way in which 
EPA's risk assessments accounted for individuals to recover from the 
effects of carbofuran between exposures; (2) EPA should have relied on 
the carbofuran human study and therefore use of the default 10X 
interspecies factor is inconsistent with

[[Page 59622]]

the ``best available data; (3) the import tolerances by themselves are 
safe and EPA should have retained them even if EPA believed tolerances 
associated with the domestic uses were unsafe; and (4) Petitioners 
claim that the combined food and water exposures are safe, based on 
FMC's drinking water estimates of a 1.1 ppb maximum concentration, 
which are guaranteed by new label restrictions submitted as part of 
objections. Finally, Petitioners raise one legal objection 
unaccompanied by a hearing request. They argue that EPA lacks authority 
to limit issues and supporting information that can be raised in 
objections and hearing to those raised in earlier comments.
    EPA denies each of the Petitioners' objections as well as their 
hearing requests. In the first instance, EPA denies Petitioners' 
objections and their hearing requests because the objections are 
inextricably intertwined with proposed changes to carbofuran's FIFRA 
registration that were not submitted until after publication of the 
final tolerance revocation rule. Objections to EPA's decision based on 
FIFRA registration amendments proposed after EPA's decision are 
irrelevant, and thus immaterial, to a challenge to EPA's decision (See 
Unit VI.C.). Secondly, an individual analysis of Petitioners' 
objections and hearing requests leads to the same conclusion for the 
reasons summarized below.
    The Petitioners' hearing requests fail to meet the statutory and 
regulatory requirements for holding a hearing. In most cases, EPA has 
denied the request on the grounds that the objection is irrelevant, and 
therefore immaterial, with regard to EPA's final tolerance revocation 
regulation. In particular, many claims are immaterial because they 
largely restate the claims in their combined comments on EPA's proposed 
rule without challenging the substance or even responding to EPA's 
explanations for the reasons that EPA declined to adopt the approaches 
or otherwise make the revisions suggested by the Petitioners in their 
comments. These claims are irrelevant to the determinations reached in 
the final rule. In several instances, EPA concluded that Petitioners 
evidentiary proffer was inadequate, because the data and information 
submitted, even if accurate, would be insufficient to justify the 
factual determination urged, or to resolve one or more of the issues in 
their favor. Further, in many cases, the evidence submitted constituted 
mere allegations and general denials and contentions, which EPA 
regulations expressly provide to be insufficient to justify a hearing. 
In addition, many of Petitioners' claims do not present genuine and 
substantial issues of fact and/or are immaterial to the relief 
requested.
    On the merits, the majority of Petitioners' objections are denied 
for substantially the same reasons given in EPA's final rule and 
response to comments. As noted, many of Petitioners' objections are 
simply their recycled comments which do not address the conclusions 
reached by EPA in the final rule. To the extent a response is even 
needed to such a stale claim, it is provided in the final rule and the 
response to comments.
    The remainder of this Unit is organized in the following manner. 
Unit VI.B describes in greater detail the requirements pertaining to 
when it is appropriate to grant a hearing request. In Unit VI.C, EPA 
generally denies all of Petitioners' objections and hearing requests. 
Unit VI.D provides EPA's response to the Petitioners legal objection 
that EPA lacks the legal authority to limit the issues and supporting 
information that can be raised in an objection and hearing to those 
raised in comments on the proposed rule. Units VI. G and I provide 
Petitioners' claims regarding EPA's risk assessment. EPA's conclusions 
on the hearing requests and objections are summarized in Unit VI.K.
    EPA has adopted a 4-part format in Units VI.E through I. for 
explaining its ruling on each of the subissues EPA identified in the 
objections. First, the Petitioners' claim and any arguments or evidence 
tendered to support that claim are described. Second, background 
information on the claim is provided including whether and how the 
claim was presented in Petitioners' comments and, if it was presented, 
EPA's reasons for denying the claim in its final rule and response to 
comments. Third, EPA explains its reasons for denying a hearing on that 
claim. Finally, EPA explains its reasons for denying the claim on the 
merits.

B. The Standard for Granting an Evidentiary Hearing

    EPA has established regulations governing objections to tolerance 
rulemakings and tolerance petition denials and requests for hearings on 
those objections. (40 CFR Part 178; 55 FR 50291 (December 5, 1990)). 
Those regulations prescribe both the form and content of hearing 
requests and the standard under which EPA is to evaluate requests for 
an evidentiary hearing.
    As to the form and content of a hearing request, the regulations 
specify that a hearing request must include: (1) A statement of the 
factual issues on which a hearing is requested and the requestor's 
contentions on those issues; (2) a copy of any report, article, or 
other written document ``upon which the objector relies to justify an 
evidentiary hearing;'' and (3) a summary of any other evidence relied 
upon to justify a hearing. (40 CFR 178.27).
    The standard for granting a hearing request is set forth in section 
178.32. That section provides that a hearing will be granted if EPA 
determines that the ``material submitted'' shows all of the following:

    (1) There is a genuine and substantial issue of fact for 
resolution at a hearing. An evidentiary hearing will not be granted 
on issues of policy or law.
    (2) There is a reasonable possibility that available evidence 
identified by the requestor would, if established, resolve one or 
more of such issues in favor of the requestor, taking into account 
uncontested claims or facts to the contrary. An evidentiary hearing 
will not be granted on the basis of mere allegations, denials, or 
general descriptions of positions and contentions, nor if the 
Administrator concludes that the data and information submitted, 
even if accurate, would be insufficient to justify the factual 
determination urged.
    (3) Resolution of the factual issue(s) in the manner sought by 
the person requesting the hearing would be adequate to justify the 
action requested. An evidentiary hearing will not be granted on 
factual issues that are not determinative with respect to the action 
requested. For example, a hearing will not be granted if the 
Administrator concludes that the action would be the same even if 
the factual issue were resolved in the manner sought.

    (40 CFR 178.32(b)).
    This provision essentially imposes four requirements upon a hearing 
requestor. First, the requestor must show it is raising a question of 
fact, not one of law or policy. Hearings are for resolving factual 
issues, not for debating law or policy questions. Second, the requestor 
must demonstrate that there is a genuine dispute as to the issue of 
fact. If the facts are undisputed or the record is clear that no 
genuine dispute exists, there is no need for a hearing. Third, the 
requestor must show that the disputed factual question is material--
i.e., that it is outcome determinative with regard to the relief 
requested in the objections. Finally, the requestor must make a 
sufficient evidentiary proffer to demonstrate that there is a 
reasonable possibility that the issue could be resolved in favor of the 
requestor. Hearings are for the purpose of providing objectors with an 
opportunity to present evidence supporting their objections as the 
regulation states, hearings will not be granted on the basis of ``mere 
allegations, denials, or general

[[Page 59623]]

descriptions of positions or contentions.'' (40 CFR 178.32(b)(2)).
    EPA's hearing request requirements are based heavily on FDA 
regulations establishing similar requirements for hearing requests 
filed under other provisions of the FFDCA (53 FR 41126, 41129 (October 
19, 1988)). FDA pioneered the use of summary judgment-type procedures 
to limit hearings to disputed material factual issues and thereby 
conserve agency resources. FDA's use of such procedures was upheld by 
the Supreme Court in 1972, (Weinberger v. Hynson, Westcott & Dunning, 
Inc., 412 U.S. 609 (1973)), and, in 1975, FDA promulgated generic 
regulations establishing the standard for evaluating hearing requests 
(40 FR 22950 (May 27, 1975)). It is these regulations upon which EPA 
relied in promulgating its hearing regulations in 1990.
    Unlike EPA, FDA has had numerous occasions to apply its regulations 
on hearing requests. FDA's summary of the thrust of its regulations, 
which has been repeatedly published in the Federal Register in orders 
ruling on hearing requests over the last 24 years, is instructive on 
the proper interpretation of the regulatory requirements. That summary 
states:

    A party seeking a hearing is required to meet a threshold burden 
of tendering evidence suggesting the need for a hearing.' [] An 
allegation that a hearing is necessary to sharpen the issues' or 
fully develop the facts' does not meet this test. If a hearing 
request fails to identify any evidence that would be the subject of 
a hearing, there is no point in holding one.
    A hearing request must not only contain evidence, but that 
evidence should raise a material issue of fact concerning which a 
meaningful hearing might be held. [] FDA need not grant a hearing in 
each case where an objection submits additional information or 
posits a novel interpretation of existing information. [] Stated 
another way, a hearing is justified only if the objections are made 
in good faith and if they ``draw in question in a material way the 
underpinnings of the regulation at issue.'' Finally, courts have 
uniformly recognized that a hearing need not be held to resolve 
questions of law or policy

    (49 FR 6672, 6673 (February 22, 1984); 72 FR 39557, 39558 (July 19, 
2007) (citations omitted)).
    EPA has been guided by FDA's application of its regulations in this 
proceeding. Congress confirmed EPA's authority to use summary judgment-
type procedures with hearing requests when it amended FFDCA section 408 
in 1996. Although the statute had been silent on this issue previously, 
the FQPA added language specifying that when a hearing is requested, 
EPA ``shall * * * hold a public evidentiary hearing if and to the 
extent the Administrator determines that such a public hearing is 
necessary to receive factual evidence relevant to material issues of 
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)). This 
language grants EPA broad discretion to determine whether a hearing is 
``necessary to receive factual evidence'' to objections (H.R. Rep. No. 
104-669, at 49 (1996)).

C. General Denial of Objections and Hearing Requests

    Petitioners' objections and hearing requests are denied in their 
entirety as irrelevant, and therefore immaterial, to EPA's 
determination in the May 15, 2009 final rule that the carbofuran 
tolerances were unsafe and could not be sustained under FFDCA section 
408. In that final rule, EPA assessed the risks from carbofuran based 
on existing uses of carbofuran, as modified by all use restrictions 
proposed by FMC. EPA concluded that the carbofuran tolerances 
substantially exceeded the FFDCA safety standard, particularly as to 
infants and children.
    Petitioners' objections and hearing requests as to that final rule 
disclose on their face their irrelevance to the conclusions reached in 
the May 15, 2009 final rule. As Petitioners summarize their objections 
on the first page of their submission:

    Petitioners disagree that the carbofuran tolerances are unsafe 
and argue that the available scientific data show that there is a 
reasonable certainty of no harm to human health from the continued 
use of carbofuran for certain specific uses and related tolerances 
under the terms for reregistration proposed by Petitioners.

    (Objections at 1) (footnote omitted) (emphasis added). As 
Petitioners' footnote to this sentence reveals, however, the proposed 
terms for FIFRA reregistration referenced by Petitioners include 
significant terms submitted to EPA on June 29, 2009, 44 days after 
publication of the final rule revoking carbofuran's FFDCA tolerances. 
In fact, the body of Petitioners' objections show that FMC's June 29, 
2009 proposed FIFRA registration amendments are inextricably 
intertwined with the claims made in the objections. Thus, Petitioners 
are actually not objecting to the conclusions in EPA's final rule; 
rather, they are suggesting that EPA might reach a different result in 
a different factual scenario.
    Objections, however, must be directed ``with particularity [at] the 
provisions of the regulation or order deemed objectionable.'' 21 U.S.C. 
346a(g)(2). The key here is that a party must file particularized 
objections to--that is, identify some type of error in--a specific 
regulatory decision. In no sense, however, can it be claimed that EPA 
erred, or that there is something objectionable, in its May 15, 2009 
file rule because EPA did not consider a proposed revision to the terms 
of the carbofuran registration that had not yet been made. EPA need not 
shoot at a moving target, much less a target that is not in existence. 
Therefore, Petitioners' objections are irrelevant, and thus immaterial, 
to the May 15, 2009 final rule; they are based on hypothetical terms of 
carbofuran use not before the Agency as it made its determination in 
that final rule.
    Moreover, it is not as if Petitioners' proposed terms for 
carbofuran use are simple, straightforward use deletions that could be 
immediately effectuated. While such a proposal is still irrelevant as a 
challenge to a prior EPA determination, such a proposal might lead EPA 
to expeditiously modify its action. Rather, Petitioners have proposed 
an unprecedented scheme involving FMC playing a role as a middleman 
between EPA and growers to ensure that carbofuran use in no one area 
exceeds a certain percentage of the cropped area. FMC has properly 
filed proposed amendments to its FIFRA registration, which would 
incorporate these new restrictions on carbofuran use and EPA will 
review these proposals consistent with the substantive and procedural 
requirements of FIFRA. At such time as these new terms of registration 
are determined by EPA to meet the standard for registration, and not 
before, would it be appropriate for EPA to consider whether the 
tolerance revoked by the May 15, 2009 rule should be re-established.
    Finally, Petitioners argue that it can raise its proposed terms of 
carbofuran use because EPA cannot limit them from putting forward new 
issues in a hearing. As explained below, EPA believes Petitioners have 
misconstrued the law on this point. However, even assuming for the sake 
of argument that Petitioners are correct that new issues can be raised 
at a hearing on objections, Petitioners admit that any newly raised 
issues must meet the standard of relevance. As explained above, 
however, objections based on terms or FIFRA registration proposed after 
EPA's final rule are irrelevant to the correctness of EPA's 
determination in that final rule.
    EPA has nonetheless evaluated each of Petitioners' objections and 
hearing requests and determined that there are alternate grounds for 
denying them. (See Units VI.E through I). EPA has undertaken this 
analysis for all of the objections despite the fact that it is not at 
all clear that those of Petitioners'

[[Page 59624]]

claims which appear to be unrelated to FMC's recently proposed 
registration amendments would either individually or collectively 
change EPA's safety determination for the carbofuran tolerances given 
the relatively high level of risk estimated for the carbofuran 
tolerances in the final revocation rule. Petitioners have certainly not 
provided any road map as to how a safety finding could be made absent 
FMC's recently-proposed registration amendments. The failure to make 
such a showing is further justification for EPA's denial of 
Petitioners' objections and hearing requests.

D. Response to Petitioners' Objection That EPA Lacks the Authority To 
Limit the Issues That May Be Raised in Objections and Hearing Requests

    1. Response to Legal Issue. Petitioners claim that EPA lacks the 
authority to restrict the issues that may be raised as part of their 
objections. Specifically, they challenge EPA's interpretation that the 
failure to raise issues or provide information during the comment 
period on the proposed rule bars consideration of such issues or 
evidence as part of submitted objections or hearings. Petitioners make 
two arguments in support of this contention: (1) That neither FFDCA 
section 408(g) on its face nor EPA's regulations implementing FFDCA 
section 408(g) limit the issues that can be raised in objections, or in 
any hearing; and (2) that even though the rulemaking phase is governed 
by 553 of the Administrative Procedure Act (APA), the hearing must be 
held in accordance with APA sections 556 and 557, which requires that 
the ``exclusive record for decision must consist of testimony and 
exhibits received at the hearing, as well as other papers filed in the 
hearing proceeding'' (Obj at 64). On this basis, the Petitioners 
conclude that all of the cases cited in the Final Rule requiring 
parties to raise all issues and information on which they intend to 
rely in subsequent proceedings are inapplicable.
    These arguments are premised on several fundamental 
misconstructions of the FFDCA section 408 and the APA. None of the 
cases they cite address the specific question of whether and how the 
requirements of section 553 of the APA apply to FFDCA section 408. And 
for many of these cases, Petitioners misquote the cases, misinterpret 
the holdings, or misconstrue language taken out of context.
    Petitioners' first argument, that neither section 408(g) nor EPA's 
regulations limit the issues that can be raised in objections or in any 
hearing, is incorrect and misses the point. As discussed at length in 
the Final Rule, the provisions of 408(g) are not to be viewed in 
isolation, but as part of a coherent statutory structure inextricably 
linked to the FFDCA's informal rulemaking procedures and section 553 of 
the APA. Petitioners concede that FFDCA section 408 establishes an 
informal rulemaking process (Obj at 62-63). As an informal rulemaking, 
the process is governed by section 553 of the APA and the case law 
interpreting these requirements, except to the extent that section 408 
provides otherwise.\5\ In this regard, it is well established that the 
failure to raise factual or legal issues during the comment period of a 
rulemaking constitutes waiver of the issues in further proceedings. 
E.g., Forest Guardians v. U.S. Forest Service, 495 F.3d 1162, 1170-1172 
(10th Cir. 2007) (Claim held waived where commenters ``failed to 
present its claims in sufficient detail to allow the agency to rectify 
the alleged violation''); Nuclear Energy Institute v. EPA, 373 F.3d 
1251, 1290-1291 (DC Cir. 2004) (``To preserve a legal or factual 
argument, we require its proponent to have given the agency a `fair 
opportunity' to entertain it in the administrative forum before raising 
it in the judicial forum.'') Native Ecosystems Council v. Dombeck, 304 
F.3d 886, 889-900 (9th Cir. 2002) (Purpose of requirement that issues 
not presented at administrative level are deemed waived is to avoid 
premature claims and ensure that agency be given a chance to bring its 
expertise to bear to resolve a claim); Kleissler v. U.S. Forest 
Service, 183 F.3d 196, 202 (3d Cir. 1999) (Policy underlying exhaustion 
requirement is that ``objections and issues should first be reviewed by 
those with expertise in the contested subject area''); National 
Association of Manufacturers v. U.S. DOI, 134 F.3d 1095, 1111 (DC Cir. 
1998) (``We decline to find that scattered references to the services 
concept in a voluminous record addressing myriad complex technical and 
policy matters suffices to provide an agency like DOI with a `fair 
opportunity' to pass on the issue''); Linemaster Switch Corporation v. 
EPA, 938 F.2d 1299, 1305-1306 (DC Cir. 1991) (declining to consider in 
challenge to final rule, data alluded to in comments but not submitted 
during the comment period, and information submitted to EPA office that 
was not developing the rule).
---------------------------------------------------------------------------

    \5\ For example, section 408(d) allows the Agency to proceed to 
a final rule after publication of a submitted petition, rather than 
requiring publication of a proposal.
---------------------------------------------------------------------------

    Moreover, EPA clearly stated in the proposed rule that the Agency 
considered that the usual requirements applicable to informal 
rulemakings would remain applicable in this informal rulemaking. The 
proposal explicitly noted that ``[i]f you anticipate that you may wish 
to file objections on the final rule, you must raise those issues in 
your comments on this proposal. EPA will treat as waived, any issue not 
originally raised in comments on this proposal'' (73 FR 44,865 (July 
31, 2008)).
    The fact that FFDCA section 408 in certain limited circumstances 
supplements the informal rulemaking with a hearing does not 
fundamentally alter the requirements applicable to informal 
rulemakings. Nor, as discussed below, does it convert this into a 
formal rulemaking, subject to the exception in section 553. The FFDCA 
section 408 establishes a unique statutory structure with multiple 
procedural stages, and delegates to EPA the discretion to determine the 
implementation that best achieves the statutory objectives. 
Accordingly, EPA interprets the notice and comment rulemaking portion 
of the FFDCA section 408 process as an integral part of the FFDCA 
process, inextricably linked to the administrative hearing. The point 
of the rulemaking is to resolve the issues that can be resolved, and to 
identify and narrow any remaining issues for adjudication. Consequently 
the administrative hearing does not represent an unlimited opportunity 
to supplement the record, particularly with information that was 
available during the comment period, but that commenters have chosen to 
withhold. For example, as discussed at greater length in Unit VI.E.2, 
both in their comments, and again in their objections, the Petitioners 
failed to provide the underlying mathematical modeling that supported 
their claim that the appropriate children's safety factor was 1X, 
rather than 4X. Instead, they presented only summary results. 
Similarly, although the Petitioners claimed in their comments to have 
conducted an alternate analysis showing that aggregate carbofuran 
exposures to children would be safe, they failed to provide the data 
and details of that assessment to the Agency. They also failed to 
provide several critical components that served to support key inputs 
into that assessment.
    To read the statute otherwise would be to render the rulemaking 
portion of the process entirely duplicative of the hearing, and thus, 
ultimately meaningless. See, e.g., FDA v. Brown & Williamson Tobacco, 
529 U.S. 120, 132-133 (2000) (Court must interpret statute as a 
symmetrical and coherent regulatory scheme, and fit, if possible,

[[Page 59625]]

all parts into a harmonious whole.) APW, AFL-CIO v. Potter, 343 F.3d 
619, 626 (2nd Cir. 2003) (``A basic tenet of statutory construction * * 
* [is] that a text should be construed so that effect is given to all 
its provisions, so that no part will be inoperative or superfluous, 
void or insignificant, and so that one section will not destroy another 
* * *''), quoting Silverman v. Eastrich Mulitple Investor Fund, 51 F.3d 
28, 31 (3rd Cir. 1995). The equities of this construction are 
particularly strong, where, as here, the information was (or should 
have been) available during the comment period. See, Kleissler, 183 
F.3d at 202 (``[A]dministrative proceedings should not be a game or a 
forum to engage in unjustified obstructionism by making cryptic and 
obscure reference to matters that `ought to be' considered and then, 
after failing to do more to bring the matter to the agency's attention, 
seeking to have that agency determination vacated'') citing Vermont 
Yankee Nuclear Power Corp. v. NRDC, 435 U.S. 519, 553-54 (1978). For 
example, one of Petitioners' exhibits is the drinking water modeling 
that served as the basis for the comments submitted on the proposed 
rule. The documents are dated well before the close of the comment 
period, and were clearly available for submission along with the 
comments (Exhibit 15). Yet they were only provided to EPA as part of 
the Petitioners' objections.
    Contrary to Petitioners' contention, EPA's interpretation is 
entirely consistent with the FFDCA's language and structure. The fact 
that the statute and regulations allow ``any person'' to file 
objections is immaterial. At issue is not ``who'' may raise objections, 
but what issues may be raised as part of the objections to justify a 
hearing. And on the relevant question, the statute is clear that only 
certain issues--those of material fact--may be raised in objections to 
justify a hearing (21 U.S.C. 346a(g)(2)(B)). EPA's regulations expand 
on this limitation, providing, among other requirements, that hearings 
will not be held on legal or policy issues, nor on the basis of mere 
allegations, nor where EPA concludes that the data and information 
submitted, even if accurate, would be insufficient to justify the 
factual determination urged (See 40 CFR 178.32). It is true that FFDCA 
section 408(g)(2)(A) provides little guidance on the objections that a 
party may raise, requiring only that parties identify the specific 
provisions challenged, and state ``reasonable grounds'' for their 
objection. But the relative silence of the statutory provision does not 
mean that EPA is required to allow parties to raise any and all 
objections; rather it means that Congress left the question of what 
constitutes ``reasonable grounds'' for EPA to resolve.
    In construing that requirement, EPA gives weight to the fact that 
408(g) is only one part of a larger, multi-stage, administrative 
process, and that the statute does not support an interpretation that 
this one phase be granted greater significance than the rest of the 
process. Also relevant is that Congress delegated broad discretion to 
the Agency to determine whether a hearing is ``necessary'' (21 U.S.C. 
346a(g)(2)(B)). Accordingly, EPA believes that whether an objection 
states ``reasonable grounds'' is to be measured against the context of 
the rulemaking, and the provisions applicable to hearing requests.
    Fundamentally, FFDCA section 408 delegates broad discretion to EPA, 
both to determine how best to harmonize the statutory process and to 
determine what constitutes ``reasonable grounds'' for objections. 
Consequently, the relevant question is whether EPA's exercise of 
discretion in requiring parties to present all available factual issues 
and evidence during the rulemaking is reasonable. It is undeniably a 
reasonable exercise of discretion to ensure that the rulemaking is not 
an opportunity for one party to waste the time and resources of all 
parties--both the government and other rulemaking participants--by 
failing to raise all of their issues or withholding information for the 
purpose of surprising the government at a later point during the 
proceeding. See, e.g., Vt. Yankee, 435 U.S. at 553-554; United States 
v. L.A. Tucker Truck Lines, 344 U.S. 33, 37 (1952) (``courts should not 
topple over administrative decisions unless the administrative body * * 
* has erred against objection made at the time appropriate under its 
practice'').
    EPA has consistently interpreted section 408 in this fashion since 
the 1996 amendments. For example, EPA previously ruled that a 
petitioner could not raise new issues in filing objections to EPA's 
denial of its Original petition. See 72 FR 39318, 39324 (July 18, 2007) 
(``The FFDCA's tolerance revocation procedures are not some sort of 
`game,' whereby a party may petition to revoke a tolerance on one 
ground, and then, after the petition is denied, file objections to the 
denial based on an entirely new ground not relied upon by EPA in 
denying the petition.''). EPA reasoned that new issues were not 
cognizable because they ``not an objection to the `provisions of the * 
* * order [denying the petition]' '' (Id.). Similarly, in a recent 
decision EPA denied NRDC's request for a hearing because they had 
failed in their original petition to raise the claim asserted in their 
objection (73 FR 42683, 42696 (July 23, 2008)). EPA noted that although 
NRDC did argue in its petition that EPA cannot make a safety finding 
without completing the endocrine screening program under FFDCA section 
408(p), it did not assert claims regarding the endocrine data and the 
children's safety factor. Citing its previous decision, EPA denied 
NRDC's objections and hearing requests as to the children's safety 
factor (Id.). In that same decision, EPA also denied a number of 
hearing requests on the ground that requestor failed to proffer 
supporting evidence; EPA opined that a failure to offer evidence at an 
earlier stage of the administrative proceeding could not be cured by 
suddenly submitting such evidence with a hearing request. (See 73 FR 
42683, 42710 (July 23, 2008) (``Presumably Congress created a multi-
stage administrative process for resolution of tolerance petitions to 
give EPA the opportunity in the first stage of the proceedings to 
resolve factual issues, where possible, through a notice-and-comment 
process, prior to requiring EPA to hold a full evidentiary hearing, 
which can involve a substantial investment of resources by all parties 
taking part * * * Accordingly, if a party were to withhold evidence 
from the first stage of a tolerance petition proceeding and only 
produce it as part of a request for a hearing on an objection, EPA 
might very likely determine that such an untimely submission of 
supporting evidence constituted an amendment to the Original petition 
requiring a return to the first stage of the administrative proceeding 
(if, consideration of information that was previously available is 
appropriate at all'').
    The two cases Petitioners cite that are specific to section 408(d) 
do not alter this assessment. Neither of those cases addressed the 
scope of the evidence that could be properly raised as part of 
objections to justify a hearing. Nor were the courts examining the 
extent of EPA's authority to impose requirements on the filing of 
objections under 408(g). Rather these courts were evaluating the scope 
of the FFDCA's exclusive review provisions, and whether the plaintiffs 
could bring a challenge to EPA policies and individual tolerance 
decisions without first exhausting the FFDCA's petition process. 
Geertson Farms v. Johanns, 439 F.Supp.2d 1012, 1022-1023 (N.D. Ca 
2006); NY v. EPA, 350 F.Supp.2d 429, 442-443 (S.D.N.Y. 2004). This 
issue is not identical to the questions at issue here: for example, the

[[Page 59626]]

court in Geertson Farms held that the plaintiffs' procedural and policy 
decisions were properly raised initially before the Agency through the 
petition process. 439 F.Supp2d at 442. Yet it is undeniable that EPA's 
regulations preclude the reliance on policy or legal issues as a 
justification for an Agency hearing.
    Nor do the Petitioners' other cases compel a different result. The 
majority of the Petitioners' cases concern FFDCA section 701(e), which 
differs in several significant respects from FFDCA section 408. Section 
701(e) imposes no requirements whatsoever on the party submitting the 
objection: ``any person may file objections * * * specifying the 
provisions of the order deemed objectionable, stating the grounds 
therefore * * *'' 21 U.S.C. 371(e)(2). This section also expressly 
provides that FDA must hold a hearing upon request: ``As soon as 
practicable after such request for a public hearing, the Secretary, 
after due notice, shall hold such a public hearing for the purpose of 
receiving evidence relevant and material to the issues raised by such 
objections.'' 21 U.S.C. 371(e)(3). In the face of this language, it is 
unsurprising that the courts held that FDA lacked discretion to deny a 
hearing. Further, under FFDCA section 701(e) the mere filing of an 
objection automatically stays the effectiveness of the challenged 
provisions. ``Until final action is taken upon such objections is taken 
by the Secretary under paragraph (3), the filing of such objections 
shall operate to stay the effectiveness of those provisions of the 
order to which the objections are made.'' 21 U.S.C. 371(e)(3). By 
contrast, section 408 grants the Administrator the discretion to stay 
the effectiveness of the regulation if objections are filed. 21 U.S.C. 
346a(g)(1). Indeed, the Petitioners' own cases specifically distinguish 
between section 701(e) and other FFDCA provisions. See Pactra 
Industries v. Consumer Product Safety Commission, 555 F.2d 677, 685 
(9th Cir. 1977) (rejecting FDA argument that FFDCA section 701 should 
be read consistently with FFDCA sections 505 and 507 to allow for 
summary judgment procedures).
    Petitioners' second argument is equally incorrect.\6\ As an initial 
matter, the parties agree that FFDCA 408 establishes a hybrid 
rulemaking procedure, with informal rulemaking initiating, and 
frequently ending, the process (74 FR 23070 (May 15, 2009)); Obj at 
62). Hybrid rulemaking is not formal rulemaking, which is the only 
rulemaking to which APA sections 556 and 557 apply. Nevertheless, 
Petitioners contend that once objections are raised, ``Congress 
required the use of a formal rulemaking procedure involving an on-the-
record hearing for resolving factual disputes.'' (Obj at 62) Nothing in 
the FFDCA section 408 or the APA supports this interpretation. And the 
cases cited in support of this argument are inapposite or misconstrued.
---------------------------------------------------------------------------

    \6\ As discussed below, it is not clear that a determination 
that a hearing, if held, must be held in accordance with APA 
sections 556 and 557 precludes EPA from exercising its discretion to 
restrict the issues and evidence that may be raised at this final 
stage of the administrative process.
---------------------------------------------------------------------------

    The APA section 553 on its face applies to all rulemakings except 
``[w]hen rules are required by statute to be made on the record after 
opportunity for an agency hearing'' (5 U.S.C. 553(c)). Under this 
language, APA section 553 will apply unless two requirements are met: 
(1) The statute requires an opportunity for a hearing as part of the 
rulemaking, and (2) the hearing is required to be ``on the record.'' 
FFDCA section 408 hearings are neither ``required,'' nor mandated to be 
``on the record.'' The case law is clear that statutes containing both 
characteristics are the hallmark of formal rulemaking, and that formal 
rulemaking is the rare exception. AT&T v. FCC, 572 F.2d 17, 21-23 (2d 
Cir. 1978) (``The APA requires trial-type hearings only `[w]hen rules 
(or adjudications) are required by statute to be made (or determined) 
on the record after opportunity for an agency hearing.' '') (citations 
omitted); Minden Beef Co v. Cost of Living Council, 362 F.Supp. 298 (D. 
Neb. 1973) (examining whether statutory provision that ``[t]o the 
maximum extent possible, the President or his delegate shall conduct 
formal hearings * * *'' makes hearings mandatory, in determinating 
whether formal rulemaking required). See also, e.g., Girard v. 
Klopfenstien, 930 F.2d 738, 741 (9th Cir. 1991) (``The APA does not 
apply because a debarment hearing is not required by statute. The fact 
that the hearing is `on the record' does not trigger an application of 
the formal adjudication provisions of section 554 of the APA''); 
Smedberg Machine & Tool v. Donovan, 730 F.2d 1089, 1092-93 (7th Cir. 
1984) (holding section 554 inapplicable to a proceeding that ``gives 
the adminsitrative law judge the discretion, rather than the obligation 
to conduct a review hearing.''). As discussed below, in contrast to 
other sections of the FFDCA, such as section 701(e), FFDCA section 408 
makes clear that a hearing is not mandatory upon request, but that EPA 
has broad discretion to determine whether a public hearing is necessary 
to receive factual evidence. See, 21 U.S.C. 346a(g)(2)(B), 
346a(g)(2)(C). See also, H.R. Rep. No. 104-669, at 49 (1996).
    The Supreme Court made clear in Florida East Coast Railway v. FLRA, 
that the circumstances under which rules are ``required to be made on 
the record after opportunity for an agency hearing'' are limited to 
those where Congress clearly indicates the intent to do so. 410 US 224, 
241 (1973). The mere fact that statute offers an opportunity for an 
agency hearing is not sufficient to bring rulemaking under scope of 
this exemption. Id. See also, U.S. v. Allegheny-Ludlum Steel, 406 U.S. 
742 (1972); NRA v. Brady, 914 F.2d 475, 485 (9th Cir. 1990) (No oral 
hearing required where statute required Secretary to ``afford 
interested parties opportunity for hearing'' and Agency regulations 
reserved right to determine whether oral hearing warranted); Wisconsin 
Gas Co v. FERC, 770 F.2d 1144, 1165-1168 (DC Cir. 1985) (APA 556 
hearing not required when statute only contained provisions requiring 
decision ``after a hearing'' and ``substantial evidence'' standard of 
judicial review); AT&T v. FCC, 572 F.2d 17, 21-23 (2d Cir. 1978) (APA 
556 hearing not required when statute only contained provisions 
requiring decision ``after a hearing'' and ``substantial evidence'' 
standard of judicial review) Philips Petroleum Co v. FPC, 475 F.2d 842, 
851-852 (10th Cir. 1973) (formal rulemaking not required even though 
statute required ``full hearing'' and Agency traditionally conducted 
trial-type adjudicative hearing).
    Unless the statute providing for agency action prescribes 
``hearings on the record,'' either in those exact words or by using 
similar words to indicate that Congress specifically intended to impose 
the full trial-type requirements of sections 556 and 557, the statute 
does not fall within section 553's exception. FL East Coast Railway, 
410 US at 241. While the absence of those words is not dispositive, 
``in the absence of these magic words, Congress must clearly indicate 
its intent to trigger the formal, on the record hearing provisions of 
the APA.'' City of West Chicago, Illinois v. NRC. 701 F.2d 632, 641 
(7th Cir. 1983) (citations omitted). See also, e.g., National 
Classification Committee v. ICC. 765 F.2d 1146, 1150-1151 (DC Cir. 
1985) (``Thus under Florida East Coast, there is a strong presumption 
that the procedural guarantees of section 553 of the APA are sufficient 
unless Congress specifically indicates to the contrary'' citing Vermont 
Yankee Nuclear Power Corp v. NRC, 435 U.S. 519 (1978)); AT & T v. FCC, 
572 F.2d at 21-23 (``The words, `on the record' have become, as the 
District of Columbia Circuit has

[[Page 59627]]

observed, a `touchstone test' for the applicability of the APA's trial-
type procedures''); Philips Petroleum Co, 475 F.2d at 851-852 (``The 
fact, as previously noted, that the Gas Act does not contain the words 
`on the record' furnishes a strong argument in support of the 
Commission's contention that informal rulemaking satisfies the 
requirements of the APA''); Minden Beef Co, 362 F.Supp. at 306-307 
(``Requiring `formal hearings' is not identical with requiring that 
rules be made on the record after opportunity for agency hearing.'') 
What is notable is that, in all cases, the court required clear 
expression that Congress specifically intended to impose full trial-
type requirements.
    Thus the question is whether Congress indicated any intent to 
entirely remove the FFDCA section 408 process from the requirements of 
553. The mere fact that FFDCA section 408 requires some (or even many) 
of the procedures applicable under section 556 and 557 does not resolve 
the question. See, e.g., National Classification Committee v. U.S., 765 
F.2d 1146, 1150-1151 (DC Cir. 1985) (Rejecting argument that formal 
rulemaking required on grounds that ``[u]nder Florida East Coast there 
is a strong presumption that the procedural guarantees of section 553 
of the APA are sufficient unless Congress specifically indicates to the 
contrary''); Association of National Advertisers v. FTC, 627 F.2d 1151, 
1165-1168 (DC Cir. 1979) (formal rulemaking not required, even though 
statute ``did order use of procedures not required in informal 
rulemaking'' such as rights to rebuttal and cross-examination at public 
hearing.); American Public Gas Association v. FPC, 567 F.2d 1016, 1065-
1067 (DC Cir. 1977) (Formal rulemaking not required by statutory 
provisions requiring ``full hearing'' and ``substantial evidence'' 
standard of judicial review).
    In fact, the language and legislative history of section 408 
provide clear indication of Congressional intent not to subject 
proceedings under these sections to APA sections 556 and 557. FFDCA 
section 408 does not reference APA sections 556 or 557 (see, e.g., 7 
U.S.C. 136d(c)(2)). By contrast, the previous version of section 408 
did reference APA section 556, and the deletion of this requirement 
provides clear evidence of Congressional intent not to exempt FFDCA 
from APA 553. Prior to the 1996 amendments, section 408(d)(5) of the 
original act, which governed the conduct of hearings, specifically 
referenced APA 556. (``Any report, recommendations, underlying data, 
and reasons certified to the Secretary by an advisory committee shall 
be made part of the record of the hearing, if relevant and material, 
subject to the provisions of section [556] of the APA.''). 21 U.S.C. 
346(d)(5). Moreover, the previous version of the statute contained 
additional language consistent with the requirement of hearings subject 
to APA sections 556 and 557; for example, the previous version of 
section 408(d)(5) repeatedly makes reference to ``testifying at such 
hearing.'' A further consideration is that several other provisions of 
the FFDCA do explicitly reference APA sections 554 or 556. Compare, 21 
U.S.C. 333(g)(3) (``A civil penalty * * * shall be assessed by the 
Secretary by an order made on the record after opportunity for a 
hearing provided in accordance with this subparagraph and section 554 
of title 5''); 21 U.S.C. 342(f)(1)(C) (requiring the Secretary, upon 
any declaration of imminent hazard under this section to ``initiate a 
proceeding in accordance with sections 554 and 556 of title 5''). The 
fact that Congress chose not to explicitly reference APA sections 556 
or 557 provides a strong indication that they did not intend to impose 
such a requirement on section 408 proceedings. See, e.g., St Louis Fuel 
and Supply Co v. FERC, 890 F.2d 446, 449 (DC Cir. 1989) (holding that 
formal hearing under APA 554 not required on that grounds that ``[w]e 
consider it significant that, unlike section 7193(c), other 
prescriptions in the DOE Organization Act expressly invoke the APA'') 
(citations omitted).
    Nor does any provision of FFDCA section 408 include the requirement 
that the hearing be ``on the record.'' By contrast, several other 
provisions of the FFDCA include that exact phrase. Compare, 21 U.S.C. 
335a(i) (``The Secretary may not take action * * * unless the Secretary 
has issued an order for such action made on the record after 
opportunity for an agency hearing on disputed issues of material 
fact.''); 21 U.S.C. 335b(b)(1)(A) (``A civil penalty shall be assessed 
* * * by an order made on the record after an opportunity for an agency 
hearing * * *''); 21 U.S.C. 335(c)(b) (``The Secretary may not take 
action * * * unless the Secretary has issued an order for such action 
made on the record after opportunity for an agency hearing on disputed 
issues of material fact.'') Under all rules of statutory construction, 
those differences are presumed to be intentional. Russello v. United 
States, 464 U.S. 16, 23 (1983) (``[W]here Congress includes particular 
language in one section of a statute and omits it in another section of 
the same Act, it is generally presumed that Congress acts intentionally 
and purposely in the disparate inclusion or exclusion'').
    Equally significant is that the language of section 408 explicitly 
grants EPA broad discretion to deny a hearing. Section 408(g)(2)(B) 
provides that EPA shall ``hold a public evidentiary hearing, if and to 
the extent the Administrator determines that such a public hearing is 
necessary to receive factual evidence relevant to material issues of 
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)) (emphasis 
added). This language grants EPA the discretion to determine whether 
the issues raised in objections are ``material'' issues of fact. 
Further, even where evidence relevant to an issue of material fact is 
proffered (essentially the standard set forth in 40 CFR 178.32), EPA 
construes the statutory language as requiring it to hold a hearing only 
where it determines it is necessary to receive proffered evidence. In 
other words, the statute grants EPA the discretion to determine that 
the issues could be resolved entirely on the basis of the existing 
written record. See Philips Petroleum, 475 F.2d at 848-849 (Formal 
rulemaking under APA 556 not required even though statute required that 
hearing be held, but ``Commission has a very broad discretion in 
determining the form of its proceedings'').
    EPA's construction is confirmed by the House Commerce Committee 
Report accompanying the final bill, which states:

    New subparagraph (g)(2)(B) allows an objector to request a 
public evidentiary hearing. The Administrator would decide whether 
[a] hearing were necessary to receive factual evidence relevant to 
material issues of fact raised by the objections. The Committee 
expects EPA to use this discretion fairly and to grant hearings to 
responsible parties on all sides.

    H.R. Rep. No. 104-669, at 49 (1996) (emphasis added). Notably, in 
an earlier version of the 1996 amendments, the House bill provided for 
a mandatory hearing during the notice-and-comment rulemaking stage of 
an EPA-initiated proceeding. [H.R. 1627, 104th Cong. Section 405 (new 
FFDCA section 408(e)(2)) (``EPA shall provide an opportunity for a 
public hearing * * *'') (emphasis added). This requirement was dropped 
prior to enactment but the contrast with section 408(g)(2)(B) confirms 
the discretionary character of the latter.
    If this were not sufficient indication of Congressional intent, 
further evidence is provided by the fact that in amending section 408, 
Congress chose not to adopt the provisions of section 701(e) that 
Petitioners cite in their objections. Clearly, Congress could have

[[Page 59628]]

adopted the same provisions found in FFDCA 701(e), or in any of the 
other comparable FFDCA provisions discussed above, but chose not to do 
so.
    EPA agrees that, when a hearing is warranted, the FFDCA requires an 
evidentiary hearing that comports with the procedures contemplated by 
408(g)(2)(B). But that is not the same as a requirement that section 
553 be inapplicable to the proceedings, or that any hearing be held in 
accordance with APA sections 556 and 557.\7\ Rather, section 408's 
provisions are consistent with APA sections 553 (b) and (c), which 
recognize the potential for hearings as part of informal rulemaking: 
``Except when notice or hearing is required by statute, * * * the 
agency shall give interested persons an opportunity to participate in 
the rule making through submission of written data, views, or 
arguments, with or without the opportunity for oral presentation.'' 5 
U.S.C. Sec.  553(b)(c) (emphasis added).
---------------------------------------------------------------------------

    \7\ EPA's regulations currently provide for a trial-type 
adjudicatory hearing. These regulations were adopted under the 
preceding statutory provision, and EPA has not yet undertaken any 
effort to revise the regulations to take into account the revised 
provisions of section 408.
---------------------------------------------------------------------------

    Finally, Petitioners' citation to case law interpreting FFDCA 
section 701(e) does not compel a different result. Petitioners claim 
that the provisions of FFDCA 701(e) are ``near identical'' to those 
under section 408, and on this basis, argue that, ``by analogy'' these 
decisions compel an identical interpretation of the requirements of 
FFDCA section 408 (Obj at 65). Petitioners are correct that section 
701(e) of the FFDCA has been held to be ``one of those statutes, few in 
number, that does require rule-making hearings to be on the record in 
accordance with APA sections 556.'' Pactra, supra, 555 F.2d 677, 685 
(9th Cir. 1977), citing Florida East Coast Railway, 410 U.S. at 237-38, 
(dictum). But in all other regards, Petitioners are incorrect.
    As previously discussed, there are several significant differences 
between the statutory language of FFDCA sections 701 and 408 that 
render Petitioners' citation to these cases inapposite. Hearings are 
mandatory upon request under section 701, and the filing of objections 
operates to automatically stay the provisions of the rule. Section 
701(e)(2) requires only that the objection ``state the grounds 
therefore,'' rather than requiring the a statement of ``reasonable 
grounds.'' See Pactra at 684 (distinguishing FFDCA section 701(e) from 
507(f) because the latter requires hearing applicants to show 
`reasonable grounds'). Further, although section 701 does not itself 
contain the requirement that the hearing be ``on the record,'' the 
legislative history of this provision indicates that Congress intended 
such hearings to be ``on the record.'' Pactra, 555 F.2d at 682-684 
(detailing FFDCA section 701 legislative history). These 
characteristics played a significant role in the court's decision that 
FDA lacked the authority to deny hearings under section 701(e) on the 
basis of summary judgment proceedings.\8\ However, as shown above, the 
legislative history of section 408 provides a clear indication of a 
contrary Congressional intent with respect to hearings under this 
section.
---------------------------------------------------------------------------

    \8\ Contrary to Petitioners' allegation, the DC Circuit has not 
``arrived at the same conclusion'' (Obj at 65). All of the 
discussion from Independent Cosmetic Manufacturers and Distributors 
v. U.S. Dept of Health, Education, and Welfare presented in their 
objections is dicta from a dissenting opinion. 574 F.2d 553, 572 (DC 
Cir. 1978).
---------------------------------------------------------------------------

    Petitioner's reliance on the ``substantial evidence'' standard in 
FFDCA section 408(i) is equally misplaced. Incorporation of that 
standard into judicial review provisions alone has been consistently 
held to be insufficient to indicate Congressional intent to impose the 
full requirements of APA sections 556 and 557 to a rulemaking. 
Wisconsin Gas Co v. FERC, 770 F.2d at 1167 (``The procedures required 
to develop this `substantial evidence' are not necessarily the strict 
adversary procedures of sections 556 and 557 of the Administrative 
Procedures Act''); Public Systems v. FERC, 606 F.2d 973, 979, n. 32 (DC 
Cir. 1979) (substantial evidence requirement in Natural Gas Act 
``carries no implications for procedures to be followed by the 
Commission in compiling the record''); American Public Gas Association 
v. FPC, 567 F.2d 1016, 1065-1067 (DC Cir. 1977) (``In our view, 
however, this requirement [of the substantial evidence standard] in the 
judicial review provision of the Act does not dictate the procedure to 
be followed, or the nature of the hearing to be held).
    The specific language of 408(i) defines the standard for the 
reviewing court; it does not describe the process by which the agency 
hearing is to be conducted. This is quite different from the language 
under 501(c) of the CWA, on which the DC Circuit relied in holding that 
hearings pursuant to APA section 554 were required. Marathon Oil v. 
EPA, 564 F.2d 1253, 1262-1265 (DC Cir. 1977). The CWA section 501(c) 
states ``[i]n any judicial proceeding * * * in which review is sought 
of a determination under this chapter required to be made on the record 
after notice and opportunity for a hearing * * *'' 33 U.S.C. 1369(c) 
(emphasis added).\9\ By contrast, FFDCA section 408(i) merely provides 
that ``[a]s to orders issued following a public evidentiary hearing, 
the findings of the Administrator with respect to questions of fact 
shall be sustained if supported by substantial evidence when considered 
on the record as a whole'' (21 U.S.C. 346a(i)) (emphasis added). It is 
also worth noting that the court expressly distinguished this case, 
which dealt exclusively with an adjudicatory proceeding, from those 
circumstances in which an agency proceeds through rulemaking. 564 F.2d 
at 1262, n. 30.
    In any event, even if section 556 did apply to hearings under 
section 408, Petitioners cannot avoid the case law under section 553 
and EPA's interpretation of the interrelationship between any hearing 
granted under section 408(g)(2) and the rulemaking preceding it. 
Petitioners cite to the general evidentiary provision in section 556(d) 
that provides that only irrelevant or immaterial evidence may be 
excluded and argue that this generic standard necessarily defines the 
scope of a hearing regardless of the statutory scheme in which it is 
embedded. However, context matters. As the DC Circuit noted, ``the 
informal procedures of section 553 of the APA and the more formal 
requirements of sections 556 and 557 are not mutually exclusive.'' 
American Public Gas Association, 567 F.2d at 1067. Even the caselaw 
relied upon by Petitioners does not suggest that section 556(d)'s 
evidentiary provision trumps all other considerations. Petitioners cite 
primarily to Catholic Medical Center, Inc. v. NLRB, 589 F.2d 1166, 1170 
(2d Cir. 1978). In that case, the Second Circuit interpreted section 
556(d) as specifying that ``an agency thus may not provide for the 
exclusion of evidence not protected by a privilege or countervailing 
policy . * * *'' Id. (emphasis added). Here, EPA has interpreted its 
authority to impose such a countervailing policy. Moreover, EPA's 
interpretation is clearly within the broad discretion granted it by the 
statute and the policy underlying the interpretation is a reasonable 
adaptation of judicial practice with regard to issues not presented in 
notice and comment rulemaking proceedings. Thus, Petitioners' technical 
and formalistic argument concerning section 556(d), which ignores the 
context of the section 408(g)(2) hearing provision, must be rejected.
    Similarly unavailing is Petitioners' argument concerning section 
556(e)'s

[[Page 59629]]

specification that the ``exclusive record for decision'' after a 
hearing is material or testimony submitted in the hearing or hearing 
proceeding. Petitioners assert that this provision somehow removes any 
limitations on what can be submitted at the hearing because ``that 
`exclusive record' is independent of whatever record may exist in the 
prior informal rulemaking * * *.'' (Obj at 64). Yet the hearing record 
is not ``independent'' of the rulemaking record in that EPA regulations 
require that the rulemaking record be included in the record of the 
hearing (40 CFR 179.179.83(a)(1)). Once again, Petitioners' argument 
fails because it considers section 556 in isolation rather than taking 
into account the context of the entire administrative proceeding in 
which the hearing is embedded.
    Finally, Petitioners complain that EPA ``raised a host of new 
issues and assertions for the first time in the Final [rule],'' and it 
would be inequitable for EPA to prevent them from raising objections on 
these new assessments. Petitioners identify ten categories of ``new 
computations and contentions'' that they claim raise issues that go 
beyond those addressed in their prior comments. With one exception, all 
of these ``new computations and contentions'' were revisions to 
analyses conducted in response to Petitioners' comments. Indeed, some 
of these were revisions undertaken in response to Petitioners' specific 
request; for example, the ``new'' BMD analyses they identify were: (1) 
Corrections made in response to an EPA error identified in their 
comments; (2) an extrapolation of BMD50 s, using the dose-
time-response model, to develop a common point of comparison between 
all studies, which they had claimed was the appropriate approach; and 
(3) a calculation generating a new dose-response model in order to 
calculate the BMD50 s for brain and RBC AChE inhibition, in 
response to Petitioners' claim that failure to do so was inappropriate 
(Refs. 24, 25, 85). Since these analyses were done at their behest, 
they can hardly complain that they present new issues on which they had 
no opportunity to comment. The Agency's underlying methodologies were 
the same as those used for the proposed rule; the analyses were based 
on information provided by the Petitioners and/or to address the 
revisions requested as part of the Petitioners' comments.
    Regarding the remaining analyses: The ``new exposure estimates for 
ground and surface water,'' as well as the ``revised dietary risk and 
drinking water assessments'' and ``new assessment of the impact of 
buffers and setbacks'' were conducted to accurately reflect the use 
under the registration, as modified by FMC's cancellation of uses and 
additional mitigation measures. The same is true for the ``new analysis 
of the various carbofuran labels;'' the analysis related to the labels 
submitted as part of the September 2008 comments. The chlopyrifos 
studies were raised in response to the Petitioners' citation to a 
subset of chlorpyrifos data. They acknowledge that the ``new literature 
citations'' were provided to address one of their contentions (Obj at 
56). The sole exception relates to EPA's calculation of carbofuran-
specific half-lives for use in the dietary risk assessment. As 
discussed in Unit VI.G.2, EPA does not reject Petitioners' challenge to 
EPA's calculation of the 186-minute half-life on the basis that it is 
untimely.\10\
---------------------------------------------------------------------------

    \10\ The Petitioners' claim that ``EPA provided new information 
concerning the raw data collected and records maintained by ORD in 
relation to its toxicology studies'' is inaccurate. EPA provided no 
new information on this topic in the final rule.
---------------------------------------------------------------------------

    A fair indication that EPA has not raised a host of new issues in 
the final rule is that, with the exception of the revised half-lives, 
Petitioners do not challenge the substance of any of the allegedly 
``new'' information. Indeed, as discussed in the sections below, 
Petitioners have in many instances failed to address any of the 
explanations or revised analyses EPA presented in the final rule.
    Ultimately, Petitioners' complaint misses the point. EPA does not 
interpret the statute and regulations to preclude the submission of any 
new information as part of the objections phase. Such a position would 
in fact be inconsistent with EPA's own regulations and past practice, 
which require that in order to support a hearing request, a party 
submit more than ``mere allegations or denials'' (40 CFR 178.32(b)(2)). 
Rather, EPA's interpretation in this regard is analogous to the 
determination of whether a final rule is the logical outgrowth of the 
proposal and the comments. For example, EPA does not reject 
Petitioners' citation to new studies in support of the contention that 
RBC AChE data are generally more sensitive than PNS tissues on the 
grounds that they are untimely. This is because these studies are 
simply more evidence supplementing the issue they fairly raised in 
their comments, and are intended to rebut EPA's response in the final 
rule. Similarly, the submission of new analyses relating to the ground 
water pH in Exhibit 14 is not considered untimely, as the issues they 
raise relating to ground water pH were fairly raised in comments and 
discussed throughout the rulemaking. Ultimately, EPA's policy is merely 
that the objections phase does not present an opportunity for parties 
to begin the process entirely anew, by raising issues or information 
that could have been fairly presented as comments on the proposed rule. 
Nor is the statute's additional procedural step an excuse to withhold 
information that was clearly available at the time of the rulemaking.
    2. Implications for FMC's Submission of New Registration Amendments 
as Part of their Objections. On June 29, 2009, in conjunction with 
their objections on the final rule, FMC Corporation submitted a request 
for EPA to amend its registration in several regards. Some of the 
requested amendments were further mitigation measures intended to 
address carbofuran's dietary risks. The most significant of these was a 
proposal intended to ensure that only 2% of any watershed would be 
treated with carbofuran. The proposal would require that, within five 
days of applying the product, all applicators report to FMC the 
following information: The location that the product will be used, 
crop, use rate, application method, acreage, and quantity applied. 
Based on this information, FMC would track the percentage in each 
watershed. ``Whenever it appears that carbofuran has been applied to 
1.75% of any watershed,'' the registrant would report that information 
immediately to EPA, ``cease further sales in any county that overlaps 
with such a watershed for that use season, and shall attempt to recall 
all unused carbofuran within such counties by offering to repurchase 
such unused product'' (Exhibit 2). Additionally, FMC requested that its 
registration be amended to require that ``based on watershed 
boundaries, FMC * * * prior to each use season, allocate to its 
distributors in a manner which will attempt to ensure that no 
distributor receives more carbofuran for sale than can be accommodated 
by the 2% watershed area cap in any watershed supplied by that 
distributor.''
    In addition, FMC proposed to add geographic restrictions that would 
prohibit use in certain parts of the country. Specifically, they 
proposed to restrict the use of carbofuran on potatoes to the three 
states: Idaho, Oregon, and to select counties in Washington. They 
proposed to restrict use on Sunflowers to only Colorado, Kansas, 
Nebraska, and South Dakota, as well as limited portions of North Dakota 
and Oklahoma. Under this proposal, use on corn would be restricted to 
Colorado, Iowa, Illinois, Indiana, Kansas, Missouri, Nebraska, and 
limited counties in Wisconsin. Further, they

[[Page 59630]]

proposed to add set-backs (i.e., areas where carbofuran could not be 
applied) ranging between 100 and 1,000 feet from drinking water wells, 
depending on the geographic area. Finally, as part of these amendments, 
FMC also requested that EPA revise its registration to permit use of 
carbofuran on pumpkins in Ohio, Illinois, and Indiana, and to cancel 
the use on pumpkins in the southeastern United States.
    As made clear in Unit VI.C., FMC's newly-proposed registration 
amendments are irrelevant to the prior determinations made in the final 
tolerance revocation rule. Further, as discussed in Unit VI.D., as a 
consequence of the failure to raise these amendments measures as part 
of their comments on the proposal, EPA considers that all issues 
arising exclusively as a result of these proposed amendments have been 
waived. There is no evident reason that FMC could not have offered 
these amendments as part of its September 2008 proposals. All of the 
information on which they rely was available in September of 2008. All 
of the risk concerns that the amendments were intended to address were 
discussed at length in EPA's proposed rule. Since 2006, EPA has clearly 
stated its determination that carbofuran's potential to leach into 
ground water and to runoff into surface water caused unacceptable 
dietary risks. EPA's methodologies for evaluating these risks have not 
changed since 2006. Indeed, EPA deferred regulatory action for several 
months, subsequent to the Agency's determination in 2006 that 
carbofuran did not meet either the FIFRA or FFDCA standard, to allow 
the Petitioners time to generate data to address the exact same issues 
these proposals are intended to address. In their comments on the 
proposed rule, Petitioners provided some mitigation measures intended 
to address issues relating to the carbofuran's leaching and runoff 
potential: Well set-backs, buffers, geographic use restrictions, and 
aerial application recommendations.
    As previously discussed, EPA provided clear notice in the proposed 
rule that issues that that were not raised during the comment period 
would be considered waived in subsequent stages of the administrative 
process (73 FR 44,865). Petitioners were well aware of this, as they 
commented that ``EPA's requirement to raise all issues in the comments 
does not appear to be legally binding'' (Ref. 18 at 118). Indeed they 
acknowledged that they ``agree that identifying disputed issues in the 
comments is efficient and desirable, and may help to narrow the issues 
arising in subsequent objections and an administrative hearing. 
Therefore, the commenters have made a good faith attempt to raise in 
these comments the principal issues of which they are aware'' (Id.).
    At this stage of the process, the statute requires the Petitioners 
to object to the conclusions and provisions in EPA's final rule, not to 
propose some new alternate license that they claim would meet the 
statutory standards (21 U.S.C. 346a(g)(2)(A) (``any person may file 
objections * * * specifying with particularity the provisions of the 
regulation * * * deemed objectionable''). In fact, one might fairly 
read their proposal as an admission that the existing license fails to 
meet the statutory standards.
    A further consideration is that the question of whether these 
amendments can be approved depends on whether the Agency eventually 
determines the amended registration meets the standards of FIFRA, which 
include considerations beyond the dietary risks evaluated under the 
FFDCA. Under FIFRA, the Agency's review of the amendments is also 
subject to a statutorily mandated schedule (established as part of the 
Pesticide Regulatory Improvement Act (PRIA)). These are no small 
matters. In terms of timing, FMC explicitly acknowledged in its letter 
submitting the proposed amendments that the amendments were subject to 
the PRIA review process, requesting that the actions be subject to the 
PRIA 8-month statutory deadline (which would establish a statutory 
deadline of February 2010 for Agency consideration of FMC's 
application). It is not clear whether FMC is arguing that its 
application be accorded a higher priority than other applications and 
be taken out of turn, or whether FMC is arguing that the consideration 
of the objections and request for hearing must be delayed until the 
FIFRA review process is completed. EPA rejects either position; 
Petitioners cannot use this tolerance proceeding to evade FIFRA's 
statutory review scheme, or use that scheme to delay this tolerance 
proceeding.
    As noted, although FIFRA incorporates the FFDCA dietary risk 
standard, FIFRA also requires the Agency to evaluate a much wider scope 
of issues in determining whether to grant new license requirements. For 
example, EPA must evaluate the impact this proposal would have on 
worker and ecological risks. In addition, EPA must carefully evaluate 
the policy implications involved in authorizing Petitioners' scheme. In 
this regard, it is worth noting that FMC's scheme is a novel one that 
raises significant policy questions that are specific to FIFRA, such as 
whether the steps proposed could be adequately enforced, which could 
affect the confidence that everybody would, in fact, comply with all 
the steps, (e.g., who would investigate whether users have properly 
notified FMC of use of the product; would users have to keep records to 
demonstrate to inspectors that they had appropriately reported use; how 
would further sales in a county be prohibited); and whether the steps 
themselves are appropriate tools from a policy perspective for dealing 
with risks associated with the use of a pesticide (e.g., is it 
appropriate to require users to report use to a pesticide manufacturer; 
is such reporting subject to approval under the Paperwork Reduction 
Act; is it appropriate public policy to limit sales in a watershed so 
that some growers may have preferential access to a product; would the 
scheme encourage early and potentially unnecessary purchase of product 
by users; under what circumstances, if any, should EPA approve label 
and license conditions that require the extra vigilance that would be 
required here of users, distributors, and state and federal 
regulators). Even if this scheme were determined independently to meet 
the FFDCA safety standard, if ultimately EPA were unable to grant the 
amendment based on the other considerations that it must evaluate under 
FIFRA, the unacceptable dietary risks would still remain. Thus, whether 
this scheme could result in a determination that the dietary risks are 
acceptable is not ultimately severable from the larger FIFRA process. 
Nor would it be appropriate to attempt to resolve FIFRA issues in a 
hearing under the FFDCA.
    Indeed it is questionable whether consideration of the proposed 
amendments would be appropriate even under Petitioners' position that 
all objections made in good faith may be presented at this stage of the 
proceeding (Obj at 61). For example, less than six months prior to 
their recent submission, the Petitioners proposed voluntarily 
cancellation of all use on pumpkins except in the Southeastern United 
States, alleging that sales data demonstrated that carbofuran was 
needed in the Southeastern U.S. In response to this amendment, which 
was submitted as part of their comments on the proposed rule, EPA 
analyzed the dietary risks based on this proposed use pattern for the 
final rule. A request, mere months later, for additional use on 
pumpkins in states with different geographic and weather conditions and

[[Page 59631]]

cancellation of the use in the Southeastern U.S., may fairly be 
considered suspect--an action intended to delay the revocation process 
by forcing the Agency to conduct yet additional analyses, rather than a 
good-faith objection.
    For all of these reasons, EPA has determined that reliance on these 
proposed amendments as a basis for raising objections to the final 
rule, or for requesting a hearing is not appropriate. Nevertheless, EPA 
evaluated the individual objections premised on the newly requested 
terms and conditions of registration. And in each case, the submitted 
materials relating to these objections and hearing requests 
independently failed to meet the statutory and regulatory requirements 
to justify a hearing, as discussed in the Units below.

E. Response to Specific Issues Raised in Objections and Hearing 
Requests Relating to EPA's Children's Safety Factor

    To more fully understand Petitioners' objection and hearing request 
with regard to EPA's choice of a 4X children's safety factor and EPA's 
responses, a little background is helpful. Section 408 of the FFDCA 
imposes a default additional safety factor for the protection of 
infants and children, to take into account the fact that children are 
frequently more sensitive to a pesticide's effects than adults. This 
default 10X safety factor can only be revised if the Agency has 
``reliable data'' to demonstrate that the alternative safety factor--or 
no safety factor--``will be safe for infants and children'' (21 U.S.C. 
346a(b)(2)(C)). In determining whether a different factor is safe for 
children, EPA focuses on the three factors listed in section 
408(b)(2)(C)--the completeness of the toxicity database, the 
completeness of the exposure database, and potential pre- and post-
natal toxicity. In examining these factors, EPA strives to make sure 
that its choice of a safety factor, based on a weight-of-the-evidence 
evaluation, does not understate the risk to children. (Ref. 79). The 
Agency's approach to evaluating whether sufficient ``reliable'' data 
exist to support the reduction or removal of the statutory default 10X 
is described below in Figure 1.
BILLING CODE 6560-50-P
[GRAPHIC] [TIFF OMITTED] TR18NO09.000


[[Page 59632]]


BILLING CODE 6560-50-C
    EPA has consistently required that data comparing the AChE 
inhibition in young rat pups (typically PND11) and adult rats be 
submitted on AChE-inhibiting pesticides, such as carbofuran, to 
determine the extent of children's potential sensitivity. The study 
measures the levels of AChE inhibition in both potentially relevant 
target tissues: The brain and either the PNS or red blood cell (RBC), 
which serves as a surrogate for the PNS. EPA required these data from 
FMC for carbofuran, and FMC on two occasions submitted the studies. 
Both sets of data, however, were rejected by EPA as scientifically 
flawed because they inaccurately measured the levels of RBC AChE.
    Despite the invalidity of the two FMC studies as to RBC AChE, EPA 
still has certain, limited RBC AChE data and other PNS-related data on 
carbofuran from other studies. These other carbofuran data indicate the 
following: (1) PNS-related effects (tremors) occur in pups as a result 
of exposure to carbofuran at low doses; (2) juveniles are more 
sensitive than adults to carbofuran based on brain measures; (3) 
juveniles are more sensitive than adults to carbofuran based on RBC 
AChE measures; and (4) the relative sensitivity of juveniles compared 
to adults as to RBC AChE is significantly greater the relative 
sensitivity of juveniles compared to adults as to brain AChE. It is 
also noteworthy that the data in adult rats showed RBC AChE was 
generally more sensitive to carbofuran's effects than brain AChE (RBC 
AChE inhibition was higher than brain at every dose except the lowest), 
although these data are of limited relevance, because they were 
conducted on adult animals rather than pups, and adult responses are 
frequently not predictive of children's responses. However, because the 
available pup RBC AChE data from EPA-ORD did not involve testing at 
doses that produced a sufficiently low level of inhibition, the data 
were not sufficient to develop a PoD for juveniles based on RBC AChE.
    Accordingly, in making its children's safety factor determination 
for carbofuran, EPA was faced with three significant issues: (1) 
Sufficient data on carbofuran that are routinely-required for AChE-
inhibiting pesticides to measure PNS effects was not available; (2) 
available data measuring the levels of AChE inhibition in brain and RBC 
indicated that juveniles were more sensitive than adults to carbofuran 
and other carbofuran data indicated that PNS-related effects could 
occur in pups at low dose levels; and (3) although the evidence on 
carbofuran as to RBC AChE inhibition in juveniles indicated that 
effects on juveniles' PNS might be the most sensitive endpoint, there 
was not sufficient data to calculate a PoD (for use in determining the 
safe dose or PAD) on these effects. Despite the incompleteness of the 
toxicity database and the evidence indicating the potential for pre- 
and post-natal toxicity at a very sensitive level, which indicate the 
need to retain a children's safety factor, EPA nonetheless determined 
that, because there was limited reliable data in juveniles, a full 
statutory default 10X was not necessary to ensure that children's 
exposures would be ``safe.'' EPA undertook a complex comparison of the 
brain and RBC AChE data in juveniles and determined that the likely 
increased level of sensitivity for RBC AChE inhibition is 4X. EPA thus 
concluded that using an additional children's safety factor of 4X 
applied to the PoD from data on brain AChE inhibition in juveniles 
would protect infants and children.
    1. Challenge to EPA's Scientific Basis for Retention of a 4X 
Children's Safety Factor. Petitioners object to EPA's conclusion that 
the lack of peripheral tissue data justifies retention of any portion 
of the children's safety factor. Petitioners raise two claims in this 
regard. First, they allege that a carbofuran PoD based on brain AChE is 
adequately protective of PNS effects. Second, they claim that RBC AChE 
inhibition data are not the best surrogate for PNS effects when brain 
data are available, and therefore, these data are not an ``appropriate 
surrogate for PNS effects'' and should not have been relied upon as the 
basis for retaining any portion of the safety factor. In support of 
these points, Petitioners submit summaries of the testimony they intend 
to offer at a hearing, along with copies of published studies that they 
allege provide evidence of the points raised in the testimony.
    In essence, these two main issues overlap, particularly with 
respect to the evidence submitted. Petitioners rely on the same studies 
to support both points. However, they are presented below separately as 
discrete issues in the interest of clarity. Supplemental to these two 
main points, EPA has identified three separate allegations made by 
Petitioners in support of this objection, which are also analyzed 
individually in this section.
    a. Objection/hearing request subissue: Whether a carbofuran PoD 
based on pup brain AChE inhibition data alone is adequately protective 
of PNS effects. Petitioners argue that by establishing the PoD on pup 
brain AChE inhibition data, EPA has adequately accounted for all PNS 
effects in pups without the need for an additional children's safety 
factor. They argue that brain data will adequately protect against PNS 
effects, based on the claim that the available data show that the brain 
is equally sensitive or more sensitive than PNS tissue. In support of 
this objection, Petitioners' submit the evidence contained in Exhibits 
4 and 6. Exhibit 4 consists of a report by Kendall Wallace, PhD, 
entitled ``Expert Report: Carbofuran FQPA Safety Factor,'' along with 
published studies conducted with OP chemicals, and other NMC chemicals 
(Ref. 17, 51, 53, 54, 59, 61, 62, 72). Exhibit 6 consists of a report 
by Lucio Costa, PhD, entitled, ``Expert Report: Carbofuran's FQPA 
Safety Factor and Interspecies Uncertainty Factor,'' as well as 
published literature studies conducted with chlorpyrifos and 
disulfoton, both OP pesticides, and a single study with propoxur, an 
NMC pesticide.
    i. Background. In the proposed tolerance revocation, EPA presented 
its rationale for retention of a children's safety factor.
    As explained in Unit IV.A, EPA uses a weight of evidence approach 
to determine the toxic effect that will serve as the appropriate PoD 
(or regulatory endpoint) for a risk assessment for AChE inhibiting 
pesticides, such as carbofuran (Ref. 78). Neurotoxicity resulting from 
carbofuran exposures can occur in both the central (brain) and 
peripheral nervous systems (PNS). In its weight of the evidence 
analysis, EPA reviews data, such as AChE inhibition data from the 
brain, peripheral tissues and blood (e.g., RBC or plasma), in addition 
to data on clinical signs and other functional effects related to AChE 
inhibition. Based on these data, EPA selects the most appropriate 
effect on which to regulate; such effects can include clinical signs of 
AChE inhibition, central or peripheral nervous tissue measurements of 
AChE inhibition or RBC AChE measures (Id). Due to the rapid nature of 
NMC pesticide toxicity it is difficult to document effects in the PNS 
or even AChE inhibition in the PNS and thus studies measuring AChE 
inhibition in the PNS are very rare for NMC pesticides. Although RBC 
AChE inhibition is not adverse in itself, EPA's policy is to use it as 
a surrogate for inhibition in peripheral tissues when peripheral data 
are not available. As such, RBC AChE inhibition provides an indirect 
indication of adverse effects on the nervous system (Id.).
    There are laboratory data on carbofuran for cholinesterase activity 
in plasma, RBC, and brain from studies in

[[Page 59633]]

multiple laboratory animals (rat, mouse, dog, and rabbits). Among these 
are three studies that compare the effects of carbofuran on PND11 rats 
with those in young adult rats (i.e., `comparative AChE studies') 
(Refs. 1, 2, 66). Two of these studies were submitted by FMC and one 
was performed by EPA-ORD. An additional study conducted by EPA-ORD 
involved PND17 rats (Ref. 63).
    The studies in juvenile rats show a consistent pattern that 
juvenile rats are more sensitive than adult rats to the effects of 
carbofuran. These effects include inhibition of brain AChE in addition 
to the incidence of clinical signs of PNS neurotoxicity, such as 
tremors, at lower doses in the young rats. This pattern has also been 
observed for other NMC pesticides, which exhibit the same mechanism of 
toxicity as carbofuran (Ref. 81). The 2008 SAP, in its review of the 
carbofuran draft NOIC, concurred with EPA that the brain AChE data 
clearly indicate that the juvenile rat is more sensitive than the adult 
rat (Ref. 36).
    The Agency does not have any AChE inhibition data for carbofuran in 
the PNS tissue of adult or juvenile animals. There is data on RBC AChE 
inhibition, which is a surrogate for PNS tissue AChE inhibition, in 
adult animals at both high and low doses, and RBC data in pups, but 
only at doses causing greater than 50% AChE inhibition (a very high 
level of inhibition). In adults, the data show that RBC is generally 
more sensitive to the effects of carbofuran than the brain, but that at 
the lowest dose tested, brain and RBC have similar sensitivity. In 
pups, the available data at higher doses show that, like adults, RBC is 
more sensitive than brain. For example, the EPA-ORD studies showed that 
RBC AChE inhibition is more sensitive than brain AChE inhibition in 
both PND11 and PND17 pups at the lowest dose tested. However, the 
lowest dose (0.1 mg/kg) in both studies missed the lower portion of the 
RBC AChE inhibition dose-response curve for pups. At the lowest dose, 
PND 11 pups had approximately 40% brain and 53% RBC AChE inhibition 
while PND17 pups had approximately 25% brain and 50% RBC AChE 
inhibition. Consequently, the Agency does not have RBC AChE inhibition 
data in pups at the low doses (i.e., those that cause only 10% 
inhibition) that are relevant to risk assessment to serve as a 
surrogate for PNS tissue data.
    EPA explained that additional evidence for the sensitivity of the 
PNS to carbofuran's effects comes from data in pregnant rats exposed to 
carbofuran that showed clinical signs that may be indicative of 
peripheral toxicity. Finally, EPA explained that data from other AChE 
inhibiting pesticides show that direct measures of peripheral nervous 
system (e.g., lung, heart, and liver AChE) can be more sensitive than 
brain AChE inhibition. To help illustrate, EPA gave an example of 
another chemical for which brain inhibition alone was not at all 
predictive of toxicity, to help explain why the lack of carbofuran data 
was so significant. The example given was fenamiphos (an OP pesticide), 
where cholinergic toxicity (e.g., tremors, miosis, salivation) was 
observed following inhibition of RBC, but not brain, even up to 
maximally tolerated doses (McDaniel and Moser, Ref. 53).
    Normally, EPA would regulate based on the most sensitive endpoint, 
which in this case would appear to be the effects on children's PNS. 
However, as discussed above, EPA lacked the information that would 
allow it to establish a PoD (or regulatory endpoint) based on the 
effects on children's PNS. EPA therefore established its PoD based on 
the AChE inhibition in pup brain. Generally, by regulating based on pup 
data, EPA would directly account for any additional sensitivity that 
children might have, because the safe levels estimated from these data 
would be the levels at which infants and children would be affected. In 
such circumstances, EPA could reduce the children's safety factor.
    But because EPA lacked the data on the PNS effects in pups at low 
doses of carbofuran, which are most analogous to the exposures that 
infants and children will receive from eating food with carbofuran 
residues, the Agency could not be confident that assessing risk using 
brain AChE inhibition would be protective of potential effects in the 
PNS for infants and children. Accordingly, EPA determined that, even 
though the Agency was relying on pup data, consistent with the 
statutory mandate that an additional safety factor be applied to 
account for children's increased sensitivity in the absence of 
information affirmatively demonstrating that no such safety factor is 
necessary, the Agency could not conclude that removal of the statutory 
default 10X would be ``safe for infants and children.'' As some 
information was available to characterize the effects on infants and 
children, EPA concluded that the full default 10X was unnecessary, and 
that it could safely reduce the factor to 4X.
    Petitioners raised many of the same assertions in their comments on 
EPA's proposed rule that they raise in their objections. For example, 
the Petitioners claimed that because EPA relied on pup brain data, no 
additional safety factor would be necessary to account for children's 
increased sensitivity, because ``brain data are a better surrogate for 
the PNS than RBC data.'' The comments also contended that RBC data are 
problematic in a number of regards, e.g., they are more variable. They 
also argued that EPA had generally relied exclusively on brain data for 
other NMC pesticides, and that to require an additional safety factor 
for carbofuran based on the lack of RBC AChE data was inconsistent with 
those other decisions.
    In the final rule and response to comments EPA responded to all of 
the Petitioners' claims, and comprehensively restated its reasoning 
that the lack of PNS inhibition data warranted retention of some 
portion of the children's safety factor for carbofuran (74 FR 68694-
68695 (May 15, 2009)). In essence, EPA explained that Petitioners had 
not presented any information that fundamentally altered the available 
risk information before the Agency. Specifically, EPA concluded that, 
given that (1) the EPA-ORD data clearly show that a surrogate measure 
of the peripheral nervous system (RBC AChE) in juvenile rats is more 
sensitive to the effects of carbofuran than brain AChE inhibition; (2) 
clinical signs consistent with toxicity to the peripheral nervous 
system were seen at very low doses of carbofuran; and (3) data from 
other AChE inhibiting pesticides show that direct measures of 
peripheral nervous system (e.g., lung, heart, and liver AChE) can be 
more sensitive than brain AChE inhibition, the Agency could not be 
confident that assessing risk using brain AChE inhibition would be 
protective of potential effects in the peripheral nervous system for 
infants and children.
    ii. Denial of hearing request. EPA is denying Petitioners' hearing 
request on this subissue because the evidence proffered, even if 
established, is insufficient to justify the factual determination urged 
(40 CFR 178.32(b)(2)). The totality of the evidence submitted fails to 
demonstrate a reasonable possibility that exclusive reliance on 
carbofuran brain data will be protective, largely because they have 
failed to proffer any evidence on several points that are critical to 
their argument. As such, the objection rests on speculation and mere 
allegation, and a hearing will not be granted on this basis (Id. See, 
e.g., 73 FR 42708 (July 23, 2008); 57 FR 6667, 6671 (February 27, 
1991)).
    It is important to remember that to obtain a hearing on EPA's 
children's safety factor decision, Petitioners must proffer more than 
evidence on whether

[[Page 59634]]

EPA erred, Petitioners must proffer evidence showing there is 
``reliable data'' supporting the children's safety factor they urge. 
Without the latter, their objection is immaterial because the default 
position is retention of an additional 10X safety factor. Accordingly, 
EPA has evaluated Petitioners' proffers on its children's safety factor 
claims in terms of whether they are sufficient to provide the 
``reliable data'' needed to justify the 1X safety factor that 
Petitioners propose.
    For purposes of resolving whether the statute requires the 
retention of a children's safety factor, the critical issue is whether 
sufficient data exists to determine the effects on children's 
peripheral nervous systems from low doses of carbofuran. None of the 
evidence submitted affirmatively addresses this question. As discussed 
in more detail below, the only evidence proffered in support of this 
objection was: (1) A subset of the available carbofuran data from adult 
animals; and (2) data, primarily in adult animals, from other chemicals 
to demonstrate that generally, reliance on brain data will be 
protective of PNS effects, and therefore EPA can assume that the same 
will hold true for carbofuran. However, the Petitioners have failed to 
submit any data to demonstrate that the effects seen in adults will be 
predictive of the effects in juveniles. They have also submitted no 
evidence specific to carbofuran that demonstrates the effects of low 
doses on children's peripheral nervous systems. This is critical 
because the evidence they do proffer on other chemicals fails to 
establish that as a general matter, reliance on brain data will always 
be protective of the effects on the PNS. The majority of the evidence 
in other chemicals actually proves that reliance on brain data is 
frequently not protective of the effects on the PNS. And the remainder 
of the evidence on this point, taken in the light most favorable to the 
Petitioners, provides only equivocal support for Petitioners. Such 
evidence, by itself, is insufficient to relieve the uncertainty that 
remains with respect to carbofuran, based on the affirmative evidence 
in carbofuran-specific data, showing that reliance on brain data may 
not be protective. And such evidence, that entirely fail to address the 
points that the statute makes central to a determination of the 
appropriate children's safety factor, cannot justify a hearing.
    When examined more closely, their overall evidentiary proffer is 
even less impressive. As discussed, much of the evidence was conducted 
in adult rats. Indeed the only evidence Petitioners submitted in 
support of this objection that was specific to carbofuran's effects on 
the PNS was data in adult rats. No evidence was submitted to 
demonstrate that adult data are generally predictive of responses in 
pups. Nor was any evidence submitted to support the assumption that 
pups will respond to low doses of carbofuran in the same way as adults. 
Thus their evidentiary proffer is effectively based on mere speculation 
that adult data will be predictive of pup responses, which cannot 
justify a hearing (40 CFR 178.32(b)(2)). As EPA previously explained in 
the proposed and final rules, responses in adult rats are not 
necessarily predictive of, or relevant to, responses in juveniles since 
the metabolic capacity of juveniles is less than that of adults (73 FR 
44864, 74 FR 23046). As such, juvenile rats can be more sensitive to 
some toxic agents. Simply put, studies that only involve adult animals, 
therefore, do not provide information on effects on the young, which is 
the focus of the children's safety factor. No matter how much evidence 
Petitioners can amass showing that brain AChE is protective of RBC AChE 
in adult animals, that does not relieve the uncertainty concerning 
potential sensitivity of PNS tissues in juvenile animals, particularly 
when all of the existing carbofuran data shows that pups are more 
sensitive than adults to the effects of carbofuran, and that clinical 
signs consistent with toxicity to the PNS were seen in pups at very low 
doses of carbofuran. Accordingly, in the absence of carbofuran data in 
pup PNS tissues or a surrogate such as RBC data, the Petitioners' 
evidentiary proffer fails to establish a reasonable possibility that 
this issue could be resolved in their favor. A hearing is not 
appropriate in such cases (40 CFR 178.32(b)(2)).
    The central tenet of this objection is that regulating based on the 
effects in the CNS will ensure that the PNS is protected. In this 
regard, Petitioners do cite to studies in juvenile animals, but all of 
them are conducted with chemicals other than carbofuran.\11\ Moreover, 
the Petitioners' evidence fails to demonstrate that the PNS can never 
be more sensitive than the CNS, or even that the PNS is typically less 
sensitive than the CNS. Rather, the evidence shows only that the CNS 
(brain) is sometimes more sensitive, and sometimes less sensitive than 
the PNS, depending on the chemical involved. Because the data do not 
show a consistent pattern, it indicates only that the relative 
sensitivity between the central and peripheral nervous systems varies 
depending on the chemical involved, which cannot establish that 
exclusive reliance on brain data as a general proposition will always 
be protective of PNS effects in pups. Nor can it establish that 
reliance on the brain data will be protective of the PNS effects in the 
case of carbofuran.
---------------------------------------------------------------------------

    \11\ Most of the studies were conducted on OP chemicals, and 
expressly caution against extending the results to NMC chemicals 
such as carbofuran; a point also raised by Petitioners' own experts 
(Ex 4, 6).
---------------------------------------------------------------------------

    When data are not available for a specific chemical, conclusions 
based on other chemicals can only be scientifically supported if it has 
been demonstrated that the conclusion is always true. If, ``in some 
cases,'' the conclusion is not true, then in the absence of data on the 
specific chemical, the conclusion cannot be made for that chemical, and 
uncertainty exists regarding the effects of the individual chemical. 
Since there are no data on the effects of carbofuran in PNS tissues or 
RBC data at low doses in pups, even assuming that they were able to 
prove that for the specific chemicals identified, the CNS is sometimes 
more sensitive than the PNS, significant uncertainty would remain 
regarding carbofuran's effects on the PNS. This is because the only 
evidence specific to the effects of carbofuran on the PNS at low dose 
levels that can be used as a comparison with the brain AChE levels is 
the adult RBC data.
    This also affects the materiality of this objection. If the adult 
RBC AChE data are not considered, as Petitioners suggest, no 
carbofuran-specific data exists to demonstrate the level of AChE 
inhibition in the PNS of either adults or pups at the low dose levels 
relevant to risk assessment. Thus, even assuming Petitioners could 
successfully establish every point they raise in this regard, the fact 
still remains that a decision maker would have no data that provides 
any information relating to the potential effects of carbofuran on a 
child's PNS. Given that FFDCA section 408(b)(2)(C) compels the 
application of a 10X safety factor in the absence of information to 
account for the presumptive sensitivity of children, the lack of any 
data bearing on carbofuran's PNS effects would require the Agency to 
apply a 10X safety factor, rather than the 4X factor applied in the 
final rule.
    A further flaw in the Petitioners' evidence is that it is 
internally inconsistent. Notwithstanding their allegations (discussed 
in subissue b below) that RBC data are inherently unreliable and should 
be discounted in favor of brain data, the carbofuran adult RBC data are 
one of the primary pieces of evidence proffered to support the claim 
that reliance on the carbofuran pup brain data will protect against all

[[Page 59635]]

potential PNS effects (Exhibit 4). As discussed in more detail below, 
the Report cites to the carbofuran data with adult rats to conclude 
that brain AChE inhibition correlated closely with RBC AChE inhibition. 
``This was further substantiated by the study published by McDaniel et 
al. (Ref. 54), where they report that the `lowest dose of carbofuran 
(0.10 mg/kg) significantly decreased brain ChE activity but not RBC ChE 
or motor activity' * * *'' (Id. at 4, 6). Yet having granted scientific 
validity to the adult RBC data, they must also concede the relevance of 
the EPA-ORD carbofuran pup RBC data, which clearly demonstrate that at 
every dose tested, RBC AChE, and therefore the PNS for which it is a 
surrogate, is more sensitive than the brain in juvenile rats exposed to 
carbofuran. They raise no challenge specific to the scientific validity 
of the EPA-ORD data, but rely only on their generic challenge that RBC 
data are inherently less reliable than brain data. No hearing is 
warranted based on such evidence. See 49 FR 6672 (February 22, 1984) 
(challenge to one of five related studies; in the absence of any 
additional data bearing on the clinical study, the objection 
constitutes nothing more than an allegation); 68 FR 46403 (August 5, 
2003) (hearing denied because cited studies only contained equivocal 
statements supporting objector's position).
    Accordingly, the sum of their evidence is no more than mere 
speculation that the effects of carbofuran exposure in the CNS will be 
protective of effects in the PNS. This falls far short of the 
``reliable data'' on the safety of infants and children needed to 
justify the entire removal of the 10X children's safety factor and thus 
cannot justify a hearing (40 CFR 178.21(b)(2)). See, e.g., 73 FR 42697 
(July 23, 2008) (denying hearing where the only evidence submitted was 
NRDC's claim that if the DDVP two-generation rat reproduction study had 
been conducted pursuant to the 1998 guidelines it might have shown 
endocrine effects at lower doses than the doses at which DDVP's 
cholinesterase effects were seen on grounds that this was mere 
speculation); 57 FR 6667 (February 27, 1992) (hearing denied to an 
objector who challenged FDA's rejection of a study for only containing 
partial histopathological data on the grounds that ``[s]peculation 
regarding data that do not exist cannot serve as the basis for a 
hearing'').
    A detailed examination of Petitioners' evidence follows below.
    (a) Testimony intended to show that brain is the appropriate 
endpoint. Petitioners allege that the ``critical effect of concern due 
to carbofuran is nervous system AChE. Brain is a direct measure of such 
toxic effects, while RBC not linked to any biological function.'' On 
this basis, they conclude that brain represents the most appropriate 
endpoint for risk assessment.
    Essentially this testimony fails to prove any dispute of material 
fact. EPA relied on the carbofuran pup brain AChE inhibition data to 
establish carbofuran's PoD. The Petitioners have not argued that PNS 
effects are irrelevant. Indeed, their submissions make clear that 
effects on the PNS are appropriate considerations in a risk assessment; 
the only point they dispute is whether brain or RBC data best account 
for those effects (Exhibits 4, 6).
    Alternatively, if they intend to argue that RBC data entirely lacks 
any scientific validity, this is contradicted in several places by 
their other objections and their own submissions. As discussed above, 
the commenters rely on the adult carbofuran RBC data to support their 
claim that reliance on the pup brain data is adequately protective of 
PNS effects. Moreover, they explicitly acknowledge that reliance on RBC 
data is scientifically valid in the context of the human data (Obj at 
13). Consequently, the submitted materials are insufficient to justify 
the factual determinations urged, and therefore fail to support a 
determination that an evidentiary hearing is warranted (40 CFR 
178.32(b)(2)).
    (b) Testimony purporting to show that reliance on brain data is 
sufficiently protective of the PNS. The Petitioners raise several 
arguments in this regard. First, they allege that, ``brain responds 
rapidly to carbofuran, which readily passes blood/brain barrier'' (Obj 
at 12-13). Petitioners' primary point, however, is that ``the extent of 
brain inhibition by carbofuran more accurately compares with the extent 
of PNS inhibition, and therefore brain data are adequately protective'' 
(Id.). In support of this claim, Petitioners cite to Exhibits 4 and 6, 
containing a mixture of ``expert testimony'' and published studies. 
None of the information contained in these exhibits is sufficient to 
establish a reasonable possibility that this issue could be resolved in 
their favor.
    Petitioners' first claim simply reiterates points made in their 
comments on the proposed rule. As explained in the final rule, EPA 
agrees that the data show that the brain responds rapidly to 
carbofuran, and that it readily passes the blood/brain barrier. 
However, evidence regarding the speed with which the brain reacts 
proves nothing with regard to the relative sensitivity of PNS tissues 
(Ref. 85 at 46). Petitioners have presented nothing that challenges the 
substance of EPA's response. Consequently, these claims do not present 
a live controversy as to a material issue of disputed fact; both 
parties agree on the facts at issue, which is that the brain responds 
rapidly to carbofuran. Moreover, a simple repetition of comments made 
on the proposal without more is insufficient to warrant a hearing. See, 
e.g., 73 FR at 42698-42699 (July 23, 2008) (denying several NRDC 
hearing requests because the objections were based on EPA's preliminary 
DDVP risk assessment, rather than the revised risk assessment published 
with the final order); 53 FR 53176 (December 30, 1988) (where FDA 
responds to a comment in final rule, repetition of comment in 
objections does not present a live controversy unless objector proffers 
some evidence calling FDA's conclusion into question); 62 FR 64102, 
64105 (December 3, 1997) (objector claimed that addition of ethoxyquin 
invalidated studies; hearing denied because objector did ``not dispute 
FDA's explanation in the final rule as to why addition of ethoxyquin 
did not compromise the CIVO studies, and provided no information that 
would have altered the agency's conclusion on this issue'').
    Petitioners' second point--that brain AChE inhibition correlates 
closely with PNS inhibition, and demonstrates that reliance on brain 
data will be protective of the PNS--is a disputed material issue of 
fact that could warrant a hearing, except that none of the evidence 
submitted in support of this point presents a reasonable possibility 
that the Petitioners could establish the points alleged. Consequently, 
they have failed to demonstrate that a hearing is warranted on this 
objection (40 CFR 178.32(b)(2)).
    (c) Exhibit 4. This exhibit consists of a report by Kendall 
Wallace, PhD, entitled ``Expert Report: Carbofuran FQPA Safety 
Factor,'' along with published studies (Ref. 17, 51, 53, 54, 59, 61, 
62, 72). The report argues that, ``it is my opinion that for 
carbofuran, the evidence indicates that inhibition of brain AChE is an 
appropriate surrogate for PNS AChE inhibition and that there is 
reasonable certainty that a PoD for carbofuran based on brain AChE 
inhibition is protective of any adverse CNS and PNS effects.'' The only 
carbofuran evidence directly cited in support of this allegation is 
data conducted on adult animals, using RBC AChE data, which they 
elsewhere try to discount. This assumes that adults and pups are 
similarly sensitive despite the carbofuran-specific evidence to the 
contrary. No evidence is discussed or

[[Page 59636]]

submitted to support this assumption. This therefore constitutes a mere 
allegation, which does not justify a hearing.
    None of the published studies conducted with other chemicals cited 
in the Report provide more than equivocal support for the points above; 
in fact, in several instances, the study results support EPA rather 
than the Petitioners.\12\ The studies contained in this exhibit fall 
into two general categories. The first group of studies consists of a 
subset of the chlorpyrifos literature--which is generally more relevant 
to the subissue discussed in the next objection, arguing that RBC data 
are not a good surrogate for the PNS--rather than demonstrating 
affirmatively that brain is a protective surrogate for the PNS. The 
second category of studies is one paper on physostigmine, a carbamate, 
that is discussed in the body of the report. All but one of these 
studies was conducted using adult rats.
---------------------------------------------------------------------------

    \12\ It is interesting to note that, in Exhibit 4, the expert 
actually faults EPA for comparing OP and NMC pesticides, saying 
``Although OP pesticides inhibit AChE, they are completely different 
from carbofuran and other N-methylcarbamates * * *:'' (Exhibit 4 at 
4). Yet the Exhibit includes papers on effects of chlorpyrifos, an 
OP, and these papers are not discussed in the text of the Exhibit.
---------------------------------------------------------------------------

    Marable, et al. (Ref. 51) and Nostrandt et al. (Ref. 59) are two of 
the chlorpyrifos studies Petitioners submitted as part of the comments 
on the proposed rule, and they contain little evidence to demonstrate 
that brain data correlate well with the PNS, and thus are generally 
protective of the PNS. Marable et al. involved chronic exposures to 
adult dogs; in addition to the fact that adult animals were used, and 
therefore provide evidence of little relevance to the question at 
issue, there are significant differences between the results of chronic 
and acute exposures. As a result of the repeated exposures, blood, 
brain and peripheral tissues were at steady state, which cannot occur 
from an acute exposure, and therefore this study can provide no 
information on the effects from acute exposures. Nostrandt et al. 
actually reported that, following a single low dose of chlorpyrifos, 
brain inhibition was less (not greater) than the inhibition obtained in 
heart which is part of the PNS (although higher inhibition was not seen 
in the diaphragm or retina, other parts of the PNS). At higher doses, 
the inhibition in brain and peripheral tissues were more similar. Thus, 
this study contradicts the Petitioners' claim that brain data will be 
protective of all PNS effects. Petitioners offer no explanation of how 
the resubmission of these studies addressed EPA's conclusion in the 
final rule that the chlorpyrifos data failed to prove their claim.
    Chen, et al. (Ref. 17), another study of chlorpyrifos, discussed 
whether plasma or RBC AChE should be used to establish a regulatory 
endpoint in humans and compared data from several animal studies, some 
of which were conducted with adults and some with pups. This is the 
only study in Exhibit 4 that contains data on pups. The results of one 
of the studies reported in Chen, et al. shows that at the lowest doses, 
inhibition was greater in the heart, which is part of the PNS, than in 
the brain (56% and 41% respectively); note that these are the data in 
adult rats reported in Nostrandt et al. (described above). Based on 
data from a developmental study of chlorpyrifos by Hoberman (Ref. 37), 
Chen et al. reported that the doses estimated to produce 50% inhibition 
in heart and brain actually show that in 5-day old pups (both males and 
females), the heart is 2-3 times more sensitive than brain. Thus, this 
study contradicts Petitioners' claim that brain data will be protective 
of PNS effects, since the PNS inhibition was greater than brain at the 
lowest doses in both adults and pups. And in fact, it supports EPA's 
concern that the absence of data at low doses is significant because 
the effects at low doses can differ significantly from those at higher 
doses. The data from Hoberman showed that at higher doses, ranging from 
30-100 mg/kg, the levels of inhibition in the brain were higher than 
the levels in the PNS (Ref. 37 at 16)--the exact opposite of what 
occurred at the lowest doses.
    The second group of studies consists of data on NMC chemicals. 
McDaniel et al. (Ref. 53) and Padilla et al. (Ref. 62) were cited in 
support of the claim that the difference in sensitivity between the 
brain and RBC is generally less for NMC chemicals. These studies were 
conducted with adult animals, and so do nothing to address the question 
before the Agency with respect to pups. These studies merely confirm 
the existing carbofuran data in adults, which shows that at the lowest 
dose tested, brain and RBC are essentially the same.
    Somani et al. (Ref. 72) is a study on another NMC chemical, 
physostigmine, in adult animals, cited to support the claim that ``in 
adult rats, brain AChE is somewhat more sensitive than RBC or 
peripheral AChE to inhibition by acute doses of physostigmine.'' As an 
initial matter, it is unclear that this study provides more than 
equivocal support for their claim; the study authors claim only that 
the brain ``appears'' to have the lowest values. However, even 
conceding that this study shows that the CNS tissues in adult rats are 
more sensitive to the effects of physostigmine than the PNS tissues, 
the data in this study is of limited relevance to the issue at hand, 
which is the effects in juveniles. Thus it is ultimately insufficient 
to affirmatively support the Petitioners' claim.
    In sum, based on the evidence contained in this exhibit, EPA 
concludes that there is not a reasonable probability that the proffered 
evidence would resolve the issue in Petitioners' favor, and that 
consequently no hearing is warranted on this basis. First, all but one 
of the studies discussed in this exhibit were conducted with adult 
animals, rather than pups. As such, they provide evidence of little 
relevance to the question of whether pups' PNS are more sensitive than 
the CNS. In the absence of carbofuran PNS data, or pup RBC data, much 
of this evidence is effectively mere speculation about whether adult 
data will be predictive of pup responses, which cannot justify a 
hearing (40 CFR 178.32(b)(1)).
    (d) Exhibit 6. This exhibit consists of a report by Lucio Costa, 
PhD, entitled, ``Expert Report: Carbofuran's FQPA Safety Factor and 
Interspecies Uncertainty Factor,'' as well as published literature 
studies conducted with chlorpyrifos and disulfoton, both OP pesticides, 
and a single study with propoxur, an NMC pesticide (Refs. 71, 19, 20, 
21, 61, 52, 41, 64, 16). According to Costa, these studies generally 
show that there was similar or greater AChE inhibition in brain than in 
the PNS tissues of heart, ileum, or the diaphragm, which Petitioners 
claim proves that reliance on carbofuran pup brain AChE inhibition data 
will necessarily be protective of all effects in the PNS (Exhibit 6 at 
3). The exhibit also references a human incident study (Ref. 50) of 
carbamate poisoning in early childhood and in adults, claiming that, 
``Lifshitz * * * showed that signs of adverse effects in the CNS, 
rather than PNS, prevailed in young children at the low dose levels 
covered by the paper.''
    EPA concludes that there is not a reasonable probability that the 
evidence contained in this exhibit would resolve the issue in 
Petitioners' favor. The results of these studies fail to demonstrate 
the point for which Petitioners cite them--that brain AChE is always 
equally or more sensitive than PNS AChE, and therefore exclusive 
reliance on brain data can be assumed to be protective. Consequently, 
the fact that Petitioners can identify examples of other chemicals, 
whether OPs or NMCs, that sometimes affect the brain more severely than 
the PNS does not prove

[[Page 59637]]

that this will be the case with carbofuran. Furthermore, in several of 
the cited examples the Petitioners misinterpret the findings, which 
actually support EPA's position.
    As explained in EPA's final rule, Petitioners are relying on only a 
subset of the chlorpyrifos data. The data, when examined in total, do 
not support a conclusion that brain data will always be protective of 
PNS effects (74 FR 23054-23055 (May 15, 2009)). But even relying solely 
on the studies Petitioners reference in this exhibit, it is clear that 
brain is not always inhibited to the same degree as peripheral tissues, 
nor is it always protective of peripheral tissues. The data in Padilla 
et al. (Ref. 61) are the only chlorpyrifos data that support a 
conclusion that reliance on the CNS data will be protective of the PNS. 
However, the Padilla study involved chronic dosing of rats via the 
feed, and as such, cholinesterase measurements reflected steady-state 
conditions. This study cannot provide information relevant to acute 
exposure. None of the other chlorpyrifos studies referenced in this 
exhibit support this conclusion. In Mattson et al. (Ref. 52), and 
Hunter et al. (Ref. 41), following a single dose to pregnant dams, 
heart and liver tissues were more inhibited than brain tissues. 
Similarly, in Richardson and Chambers (Ref. 64), where repeated doses 
were administered to pregnant dams, at both the low and high doses, the 
lung tissue was more inhibited than the brain tissue in the one-day old 
pups. In Carr et al. (Ref. 16), the results were more equivocal; in a 
repeated dosing study using pups of varying ages, whether brain or 
peripheral tissues were most inhibited depended on the age of the pups 
and the dose. Nevertheless, Carr (2001) showed that brain inhibition 
decreased as the age of the pups increased, even though inhibition in 
the heart tissues did not. In other words, the submitted material only 
supports a conclusion that brain is sometimes inhibited by chlorpyrifos 
to the same degree as the peripheral tissues, and in reality, the 
studies show that brain is often inhibited to a lesser extent than 
peripheral tissues. This cannot support a conclusion that reliance 
exclusively on brain data will necessarily be protective in the absence 
of some additional carbofuran-specific evidence.
    The results are similar for the disulfoton studies. Schwab et al. 
(Ref. 71) shows that after both a single dose and repeated doses, the 
brain and peripheral tissues were equally inhibited. However, these 
results are contradicted by Costa et al. (Ref. 19) and Costa and Murphy 
(1983), where the results varied depending on the dosing and the brain 
area examined. In Costa and Murphy (Ref. 21), diaphragm tissues were 
more inhibited than brain tissues after a single dose of disulfoton, 
while after repeated doses, brain and diaphragm tissues were similarly 
inhibited. Thus, the relative sensitivity between CNS and PNS changes 
with repeated dosing, and these studies provide no information on RBC 
inhibition with which to compare the other tissues.
    Finally, the Lifshitz study does not support the claim for which it 
was cited. The study presents no data on the dose levels associated 
with the poisoning incidents, and in fact concludes that there was 
``insufficient information to compare the doses ingested by [adults and 
children].'' However, based on the symptomology reported (comas, 
stupor, and severe hypotoxicity) it is likely that the doses were high, 
not low, as the Report claims. Also, this study cannot be used to 
discount PNS effects in children; a large percentage of the children 
clearly showed PNS effects (myosis, diarrhea). In addition, because 
this was a retrospective study of patients admitted to a hospital 
intensive care unit, given the severity of some of the CNS symptoms, 
such as comas, it is not unlikely that even if the subjects also showed 
PNS symptoms, they were not reported. Finally, the study authors' 
conclusion was that in children, the ``clinical presentation [of 
carbamate poisoning] differs from adult poisoning manifestations'' 
(Ref. 50). Or in other words, that the effects in adults from exposure 
to carbamates such as carbofuran are not necessarily predictive of the 
effects in children. It is difficult to see how this study could be 
fairly argued to support Petitioners' allegations.
    In conclusion, the totality of the evidence in Exhibits 4 and 6 
fail to support Petitioners' contention. As shown in Table 1 below, the 
majority of the study results demonstrate that the PNS is frequently 
more sensitive than the CNS. The remainder, taken in the light most 
favorable to the Petitioners, provide merely equivocal support.

                                    Table 1--Summary of Petitioners' Studies
----------------------------------------------------------------------------------------------------------------
                                                                                           Is CNS protective of
                                             Study design         Relative inhibition              PNS?
----------------------------------------------------------------------------------------------------------------
                                              Chlorpyrifos Studies
----------------------------------------------------------------------------------------------------------------
Padilla et al. 2005..................  Single dose, adults....  RBC > brain [ap]         Yes (same sensitivity).
                                                                 diaphragm.
Mattsson et al. 2000.................  Single dose, pregnant    RBC > heart > brain....  No.
                                        dams.
Hunter et al. 1999...................  Single dose, pregnant    Liver > brain..........  No.
                                        dams.
                                                                Blood not measured.....
Richardson and Chambers 2003.........  Repeated doses to        Low dose, lung > serum   No.
                                        pregnant dams,           [ap] brain > heart.
                                        measured pups at 1 day  High dose, lung > brain
                                        old (not direct dose).   [ap] heart > serum.
                                                                Note, serum has only
                                                                 [ap] 50% AChE, not
                                                                 true measure of AChE.
Carr et al. 2001.....................  Repeated doses to pups.  PND6: brain [ap]         Not always, depending
                                                                 diaphragm > heart [ap]   on age, dose, and
                                                                 lung > skeletal muscle   brain region.
                                                                 [ap] serum.
                                                                PND10: heart [ap]
                                                                 hindbrain [ap]
                                                                 diaphragm [ap] lung >
                                                                 skeletal muscle >
                                                                 forebrain [ap] serum.
                                                                PND16: heart [ap] lung
                                                                 > brain..
                                                                PND20: heart > lung >
                                                                 brain..
                                                                PND25: brain > PNS.....
                                                                Brain inhibition
                                                                 decreased with age,
                                                                 heart did not.

[[Page 59638]]


Nostrandt et al. 1997 (also cited in   Acute dose, adults.....  RBC > heart > brain >    No.
 Chen et al. 1999).                                              diaphragm.
Hoberman 1998 as cited in Chen et al.  Repeated doses to        RBC > heart > brain....  No.
 1999.                                  pregnant dams,
                                        measured in pups at 5
                                        days old (not direct
                                        dose).
----------------------------------------------------------------------------------------------------------------
                                               Disulfoton Studies
----------------------------------------------------------------------------------------------------------------
Schwab et al. 1981...................  Single dose............  heart [ap] ileum [ap]    Yes, similar
                                       Repeated doses.........   brain.                   sensitivity.
                                                                brain [ap] ileum >
                                                                 heart.
                                                                No blood measured......
Costa et al. 1981....................  Single dose............  Brain > ileum..........  Not always, depends on
                                       Repeated doses.........  Forebrain > ileum >       dosing paradigm and
                                                                 hindbrain.               brain region.
                                                                Brain [ap] ileum.......  Not consistent within
                                                                                          same study.
                                       Repeated doses.........  No blood measured......
Costa and Murphy 1983................  Single dose............  Diaphragm > brain......  Not always, depends on
                                       Repeated doses.........  Brain [ap] diaphragm      dosing paradigm.
                                                                 [ap] plasma..
                                                                Note, plasma has only
                                                                 [ap] 50% AChE, not
                                                                 true measure of AChE.
----------------------------------------------------------------------------------------------------------------

Accordingly, Petitioners' proffer is facially insufficient because 
there is no reasonable possibility that it can establish a necessary 
element of Petitioners' objection--that there are ``reliable data'' 
that show it would be safe for infants and children to remove entirely 
the 10X children's safety factor.
    iii. Denial of objection. The objections do not address the 
fundamental issue that EPA is required by the statute to resolve: Are 
there `reliable' data to support reduction or removal of the statutory 
10X for protection of infants and children? The statute compels that 
EPA may only revise the 10X default safety factor if, ``on the basis of 
reliable data'' EPA can conclude that the alternative safety factor 
will be ``safe'' (21 U.S.C. 346a(b)(2)(C)). The statute also requires 
EPA to account for the ``completeness of the toxicity data'' in making 
this determination (Id). In this case, the Agency concluded that there 
are sufficient data to reduce the 10X safety factor but there is 
insufficient information to justify removing the factor entirely.
    Similar to other AChE inhibiting pesticides, carbofuran can affect 
both the central and peripheral nervous system. Because the relative 
sensitivity of the central and peripheral nervous system varies among 
pesticides and the children's safety factor should account for the most 
sensitive toxicity endpoint, the Agency considers the availability of 
data in both the central and peripheral nervous systems important in 
its safety factor evaluation.
    As shown in Figure 1, above, there are several datasets that 
evaluate the effects of carbofuran on the central nervous system (e.g., 
brain AChE inhibition) in juvenile rats. There are no AChE data from 
peripheral tissues. Lack of peripheral AChE data is typical of NMCs due 
to the rapid reactivation of AChE. As a matter of science policy, the 
Agency typically uses AChE data from blood, particularly RBCs, as a 
surrogate measure for the peripheral nervous system (Refs. 76, 87). In 
the case of carbofuran, RBC AChE data from two separate studies 
submitted by FMC are considered unreliable and unusable in human health 
risk assessment (Ref. 83). Data from EPA's ORD includes high quality 
RBC AChE data, but only high doses were used in the ORD studies. Data 
at the low end of the dose response curve are not available for 
assessing the effects in juvenile rats, which are the doses relevant 
for human health risk assessment. Thus, because reliable data are 
available to assess affects on the CNS and some surrogate data are 
available to assess the PNS, the Agency believes that the children's 
safety factor can be reduced. However, this factor cannot be completely 
removed since the available carbofuran data show that RBC AChE 
inhibition in pups is more sensitive than brain AChE inhibition.
    Given that (1) data from other AChE inhibiting pesticides show that 
direct measures of peripheral nervous system (e.g., lung, heart, and 
liver AChE) can be more sensitive than brain AChE inhibition; (2) a 
surrogate measure of the peripheral nervous system (RBC AChE) is more 
sensitive in juvenile rats to carbofuran; and (3) clinical signs 
consistent with toxicity to the peripheral nervous system were seen at 
very low doses, the Agency can not be confident that assessing risk 
using brain AChE inhibition is protective of potential effects in the 
peripheral nervous system for infants and children. For example, in the 
first FMC-sponsored comparative ChE studies (Ref. 4) every pup at the 
0.3 mg/kg dose group exhibited tremors. The range-finding portion of 
the second FMC-sponsored comparative ChE study (Ref. 1) resulted in 
tremors in rats exposed to 0.3 mg/kg carbofuran (\2/5\ males and \2/5\ 
females) within 15 minutes post-dosing.
    Additional evidence for sensitivity of the PNS comes from 
carbofuran data in pregnant rats that showed clinical signs that may be 
indicative of peripheral toxicity. The California Department of 
Pesticide Regulation (CDPR) has calculated a BMD10 and 
BMDL10 of 0.04 and 0.03 mg/kg/day, respectively, for mouth 
smacking and chewing in pregnant rats exposed to carbofuran. These 
signs are early indicators of toxicity from some cholinesterase 
inhibitors (Ref. 56). This is notable for two reasons. First, 
cholinergic toxicity (e.g., tremors, miosis, salivation) may be 
observed following inhibition of blood, but not brain, cholinesterase. 
This was the case with fenamiphos (an OP pesticide), even up to 
maximally tolerated doses (Ref. 53). Second, the BMDL10 from 
the mouth smacking and chewing in pregnant rats is similar to that 
being used by EPA for brain AChE in juveniles. The similarity of the 
CDPR BMD in adults and EPA's BMD in juveniles is striking because all 
of the available data show that pups are more sensitive than adults to 
carbofuran toxicity. This therefore suggests that behavioral effects 
and/or clinical signs may be occurring in juvenile animals at lower 
doses, but which cannot be detected, in part due to the challenges

[[Page 59639]]

with assessing clinical signs in juvenile rats. As noted by the SAP, 
this ``limitation reflects the limited range of toxic signs detectable 
in very young pups (p. 54).'' This provides further support that the 
lack of pup data at lower doses is significant, because the Agency 
cannot fully evaluate the behavioral effects on juvenile animals.
    Further support for the Agency's concern comes from other clinical 
reports of the effects of carbamate poisoning in children. For example, 
Lifshitz reported that all children presented with CNS symptoms (coma, 
stupor), but CNS symptoms were observed in only 54% and 23% of children 
as reported by Zweiner and Ginsburg (1988) and El-Naggar et al. 2009 
(Refs. 91, 26). Peripheral muscarinic symptoms were the most commonly 
reported (73% and 100%) signs of toxicity in these latter two reports. 
These markedly different findings emphasize that conclusions cannot be 
unequivocally drawn from only one study.
    In addition, Petitioners' own data show that effects can differ 
significantly between high and low doses. In Chen, for example, the 
data from Hoberman showed that at the lowest doses the levels of 
inhibition were higher in the PNS than in the brain, but at higher 
doses, the levels were higher in the brain.
    Thus, for a number of reasons, the Agency has concerns that 
children's PNS may be more sensitive to the effects of carbofuran than 
the CNS. This concern is the basis for retention of a portion of the 
children's safety factor.
    The carbofuran RBC data in adult animals does not resolve this 
question. There can be substantial differences in response between pups 
and adults, and, as noted, the data show clearly that pups are more 
sensitive to the effects of carbofuran. It is not unusual for juvenile 
rats, or indeed, for infants or young children, to be more sensitive to 
chemical exposures as metabolic detoxification processes in the young 
are still developing. Because pups are more sensitive than adult rats, 
data from pups provide the most relevant information for evaluating 
risk to infants and young children and are thus used to derive the PoD. 
In addition, typically (and this is the case for carbofuran) young 
children (ages 0-5) tend to be the most exposed age groups because they 
tend to eat larger amounts of food per their body weight than do 
teenagers or adults.
    b. Objection/hearing request subissue: Reliance on RBC AChE 
inhibition data as a surrogate for PNS effects. This objection also 
challenges EPA's decision to retain some portion of the presumptive 10X 
children's safety factor, rather than remove it entirely. As explained 
above, EPA retained a portion of the presumptive 10X children's safety 
factor because of the absence of sufficient data on PNS effects in 
juveniles and the uncertainty created by the limited data relevant to 
the PNS that showed greater sensitivity in juveniles. In the previous 
subissue, Petitioners argued that in fact there is no uncertainty 
created by the lack of low dose RBC data and the finding of sensitivity 
in the RBC AChE data because brain AChE data is protective of PNS 
effects. In this subissue, Petitioners attempt to buttress their first 
argument by claiming that RBC AChE data are not an ``appropriate 
surrogate'' for PNS effects, and should not have formed the basis for 
retention of any portion of the children's safety factor.
    Petitioners do not argue that RBC data are entirely irrelevant, but 
rather that brain data are ``preferred.'' They raise several points in 
support of this contention; first, that ``RBC AChE inhibition data are 
only preferred for risk assessment purposes in two circumstances: (1) 
Where the PoD is set using data from human studies where only RBC data 
are available or (2) where data from the relevant target tissues are 
unavailable.'' They allege that, despite the absence of carbofuran data 
in the PNS tissues, brain is preferred in this case because the brain 
is ``target tissue'' from the nervous system, and because brain data 
are a ``better predictor'' of PNS effects than RBC. As further 
evidentiary support, they cite to evidence from OP studies that RBC 
AChE can ``in some cases'' be inhibited to a greater degree than either 
PNS or brain AChE, and therefore reliance on RBC AChE data can 
overstate potential PNS effects. They also argue that RBC AChE is more 
variable and less reliably measured at low response levels, such as 10% 
AChE inhibition. The evidence in Exhibits 4 and 6 is also proffered in 
support of this objection.
    i. Background. EPA's well-established policy when evaluating 
cholinesterase-inhibiting compounds is to rely on data in the target 
tissue where it is available (Ref. 76). As noted in the preceding 
section, measures of AChE inhibition in the PNS are rarely collected 
for NMC pesticides. And in fact, there are no carbofuran data measuring 
effects in PNS tissues. But in the absence of target tissue data, as a 
matter of science policy, EPA typically uses RBC AChE inhibition data 
as an indicator of possible effects on AChE in the PNS for number of 
reasons. (Ref. 76 at 32). Although RBC AChE inhibition is not adverse 
in itself, it is a surrogate for inhibition in peripheral tissues. As 
such, RBC AChE inhibition provides an indirect indication of adverse 
effects on the nervous system (Id.).
    Petitioners raised many of the same issues raised in the objections 
in their comments on the proposed rule. For example, they argued that, 
``as a matter of science policy, brain AChE inhibition is the preferred 
endpoint over RBC AChE inhibition.'' They also argued that no 
physiological function has been demonstrated for RBC, and RBC AChE 
inhibition is not itself an adverse effect.
    In the final rule, EPA responded to each of their comments, but 
concluded that no information had been submitted to justify altering 
the Agency's general policy that reliance on RBC is appropriate as a 
surrogate for PNS effects in the absence of direct measurements in PNS 
tissues.
    ii. Denial of hearing request. This subissue does not raise a 
dispute of material fact. There is no dispute regarding many of the 
facts raised in this objection: When data in the target tissue are 
available, it is preferred over a surrogate. RBC AChE can be more 
variable and less reliably measured at low response levels than brain 
AChE. RBC AChE inhibition can, in some cases, be more extensive than 
PNS AChE inhibition. Equally, there is no dispute that no physiological 
function has been demonstrated for RBC, and RBC AChE inhibition is not 
itself an adverse effect. All of these points are explicitly recognized 
in EPA's Cholinesterase policy and in the tolerance revocation 
rulemaking record, and relate purely to the ease or wisdom of relying 
on these measures rather than others, as opposed to the scientific 
invalidity of such data. The only point on which there is a dispute is, 
given that there is no data in the target tissues of the PNS, which 
data--brain or RBC--is ``preferred.'' The Petitioners expressly 
acknowledge this to be the issue: ``There are other surrogate measures 
of PNS AChE that could have been selected by OPP, such as brain AChE'' 
(Exhibit 4 at 5). This is clearly a question of scientific policy, 
since both EPA and the Petitioners agree on the scientific validity and 
relevance of RBC AChE inhibition data. As they expressly acknowledged 
in their comments, the choice of which surrogate to use is a matter of 
``science policy'' (Ref. 18). Indeed, Petitioners explicitly concede 
the propriety of relying on RBC data ``where data from the relevant 
target tissues are unavailable, or when relying on human data, where 
RBC AChE inhibition data are the only data available (Obj at 13). 
Hearings are not

[[Page 59640]]

appropriate for debating questions of policy (40 CFR 178.32(b)(1)).
    Nor does the proffered evidence present any other issue that would 
warrant a hearing. The evidence submitted in Exhibits 4 and 6 on this 
point only relates to the question of whether brain data can sometimes 
correspond more closely with PNS effects than RBC AChE data, rather 
than the question of whether the RBC data are scientifically invalid. 
Or in other words, the submitted materials relate only to the point 
that reliance on RBC data is unnecessarily conservative, because 
sometimes it overestimates the potential PNS effects, rather than to 
the factual question of whether RBC data bears no relation whatsoever 
to PNS effects. Unless Petitioners can show that RBC AChE is not 
related to CNS effects generally or specifically for carbofuran, or 
that brain AChE is protective of CNS effects generally or specifically 
for carbofuran, then the mere fact that RBC AChE may be a conservative, 
or even very conservative, indicator of PNS effects is simply 
immaterial to the question of whether there are ``reliable data'' to 
justify removing the presumptive 10X children's safety factor in the 
absence of sufficient RBC AChE data. As shown in the discussion of 
subissue 1, the Petitioners' evidence does not demonstrate that 
reliance on juvenile brain data as a surrogate for effects in the 
juvenile PNS will guarantee that the levels chosen on that basis will 
be predictive of all PNS effects from carbofuran, because the PNS 
effects occur only at the same or higher doses than those that produce 
effects on the brain AChE--i.e., that the brain data ``bound'' all 
potential PNS effects. Nor, as discussed below, does any of 
Petitioners' evidence support a conclusion that RBC AChE is unrelated 
to PNS effects.
    Indeed, much of the evidence in the Exhibit 4 and 6 Reports is 
ultimately an irrelevance, and thus fails to present a material factual 
dispute. Instead of focusing the stated objection--RBC AChE is 
inappropriate marker for CNS effects--the Reports attempt to link EPA's 
children's safety factor decision to findings concerning chlorpyrifos 
(Exhibit 4 at 4). In fact, a fair portion of the Report in Exhibit 6 is 
dedicated to a rebuttal of EPA's conclusion that the majority of the 
more recent and more relevant chlorpyrifos evidence did not support 
Petitioners' contention. EPA, however, has been clear throughout the 
rulemaking that the basis for retention of a children's safety factor 
has been the absence of carbofuran data to determine the levels of 
exposure that will be protective of children's PNS, in the context of a 
statutory provision that expressly requires EPA to account for missing 
data. EPA's point in discussing the chlorpyrifos data--which 
Petitioners initially raised as relevant--was simply that it showed 
that because peripheral tissues can be more sensitive than central 
nervous system tissues, the absence of data addressing carbofuran's 
effects on the PNS is highly relevant. Whatever the chlorpyrifos data 
show cannot resolve the extent of carbofuran's risks. As the 
Petitioners' experts themselves point out, ``Even conceding that [EPA's 
conclusion in the final rule that peripheral tissues are often shown to 
be more sensitive than brain tissue following exposure to chlorpyrifos] 
may be true, it is still unclear how this would be relevant to 
carbofuran * * *'' (Exhibit 6 at 3). Accordingly, this evidentiary 
submission fails to demonstrate that a dispute exists on a question of 
material fact.
    Finally, their submission provides an inadequate basis on which to 
grant a hearing; because evidence is not proffered on critical points, 
the objection ultimately rests on allegation, speculation, and general 
denials (40 CFR 178.32(b)(2)). As discussed in preceding section, the 
majority of the evidence comes from adult data, which are of limited 
relevance. Further, and more significantly, the evidence fails to 
demonstrate that brain data always--or even more frequently than not--
correlates more closely with PNS effects than RBC AChE data. Instead, 
the proffered evidence only demonstrates that whether brain or RBC data 
correlate better with actual PNS effects can vary depending on the 
chemical. This, therefore, cannot resolve the question as to whether, 
in the case of carbofuran, brain AChE data will necessarily correspond 
more closely with the PNS. Finally, as also discussed in the preceding 
section, Petitioners' argument is internally inconsistent, because they 
rely on carbofuran adult RBC AChE data to support their argument that 
exclusive reliance on the brain data will be protective of potential 
PNS effects in pups. No hearing is appropriate where the proffered 
evidence fails to prove the points for which it is offered, or offers 
merely equivocal support (See, 73 FR 42705 (July 23, 2008) (hearing 
denied because published articles focus on an issue not applicable to 
the facts of the case at hand); 68 FR 46405-46406 (August 5, 2003) (a 
hearing was denied because the cited studies only contained equivocal 
statements)).

A detailed examination of Petitioners' evidence follows below:

    (a) Exhibit 4. As discussed in the previous objection, this exhibit 
consists of a report, along with published studies. The Report 
criticizes EPA for assuming that RBC AChE inhibition provides ``a 
stronger and more quantitative concordance with the sensitivity of AChE 
of the PNS to inhibition by carbofuran,'' on the ground that EPA failed 
to cite to evidence to support this inference (Exhibit 4 at 5). In the 
absence of such evidence, the report concludes that, ``one cannot 
discount the plausibility that brain AChE may be a more quantitative 
and representative surrogate measure of PNS sensitivity'' (Id). To 
support this allegation, the report argues that the cited NMC data show 
that the difference in sensitivity between brain and RBC shown with NMC 
chemicals is less than the differences seen with OP chemicals, citing 
studies by Padilla et al. (Ref. 62) and McDaniel et al. (Ref. 54). In 
this regard, the Report actually misquotes McDaniel et al. The Report 
claims that the paper concluded that there was a stronger correlation 
between brain AChE inhibition and motor activity. The study actually 
concluded that there was little difference between brain AChE 
inhibition and RBC AChE inhibitions (``higher correlation for brain and 
motor activity compared to RBC were not significantly different.'') 
(Ref. 54). In any event, the Report's equivocal conclusion that ``one 
cannot discount the plausibility'' that brain AChE might be the most 
representative measure of PNS effect is, on its face, insufficient 
grounds to overcome the statutory presumption for retention of the 
additional 10X children's safety factor in the face of the evidence of 
children's additional sensitivity to carbofuran, and the lack of 
carbofuran data in PNS tissues or in a surrogate for such tissues, RBC 
AChE.
    Chen et al. (Ref. 17), which was discussed at length in the earlier 
objection, evaluated whether plasma or RBC AChE should be used to 
establish a regulatory endpoint; it did not evaluate whether brain AChE 
would be an appropriate surrogate for PNS effects. It is true that the 
authors conclude that ``[i]nhibition of RBC AChE activity is 
consistently exhibited at lower dosages of chlorpyrifos than those 
required to result in clinical symptoms of OP toxicity, or alterations 
in cognitive functional responses.'' However, since the study authors 
ultimately concluded that, ``inhibition of RBC AChE activity is an 
appropriate surrogate for measurement of chlorpyrifos exposure and 
provides a conservative endpoint for establishing appropriate margins 
of

[[Page 59641]]

safety for both adults and infants,'' it is difficult to see how this 
could be argued to provide unequivocal support for Petitioners' 
objections.
    Exhibit 6. This exhibit consists of a report by Lucio Costa, PhD, 
entitled, ``Expert Report: Carbofuran's FQPA Safety Factor and 
Interspecies Uncertainty Factor,'' as well as published literature 
studies. The report discussed the results of several published studies 
that they claim demonstrate that ``where available, brain AChE 
inhibition data provide a superior surrogate'' to RBC data because ``in 
some cases RBC AChE may overestimate PNS AChE inhibition, while in 
other cases * * * RBC AChE inhibition may underestimate actual AChE 
inhibition in the PNS.'' In support of this allegation, the report 
references data from several studies conducted with chlorpyrifos and 
disulfoton, both OP pesticides, and a single study with propoxur, an 
NMC pesticide (Refs. 16, 19, 20, 21, 41, 52, 61, 64, and 71). According 
to the Report, these studies generally show that there was similar or 
greater AChE inhibition in brain than in the PNS tissues of heart, 
ileum, or the diaphragm, which Petitioners claim proves that reliance 
on carbofuran pup brain AChE inhibition data is more predictive of all 
effects in the PNS. The exhibit also references a human incident study 
(Ref. 50) of carbamate poisoning in early childhood and in adults, 
claiming that, ``Lifshitz * * * showed that signs of adverse effects in 
the CNS, rather than PNS, prevailed in young children at the low dose 
levels covered by the paper.''
    In its denial of the hearing request on the previous issue, EPA 
examined the results of the studies in this exhibit at length, and 
demonstrated that the results of the studies failed to support a 
conclusion that brain data correlate more closely to PNS effects than 
RBC data. Indeed, in most of these studies, brain AChE inhibition 
poorly reflected the AChE inhibition in PNS tissues. For example, the 
Carr et al. study results, reproduced in Table 1 of Exhibit 6, showed 
that for PND 10, 16, and 20 rat pups, the heart tissue had the greatest 
levels of inhibition, and that PND 16 and 20 rat pups had greater 
levels of inhibition in lung tissue than in the brain (Ref. 16 at 3). 
Further, since the study was conducted with serum, which contains no 
RBC, it is unclear how this study could prove that brain data are a 
better indicator of PNS effects than RBC data.
    The remainder of the report consists of criticisms of EPA's 
conclusions, and contentions that EPA was inconsistent, without 
citation to biological evidence to support these claims. For example, 
the Report addresses EPA's rejection of the Bretaud study in goldfish 
on the grounds that the ``distribution of carbofuran across fish and 
mammalian tissues may be quite different,'' by criticizing EPA for 
failing to provide ``evidence or a citation to support this point'' 
(Exhibit 6 at 1). But they cite to nothing demonstrating the similarity 
of fish and mammalian tissues or otherwise supporting their proposed 
extrapolation across taxa; at this stage of the administrative process 
the obligation is on the Petitioners to come forward with evidence to 
call EPA's conclusions into question. See, 73 FR 42683, 42706, July 23, 
2008 (``NRDC does no more than state `we are aware of no statistical 
test' which would support EPA's use of the Gledhill data. As EPA's 
regulations make clear, a mere `denial' of an EPA position is not 
enough to satisfy the standard for granting a hearing.''); 53 FR 53176, 
53199, December 10, 1982 (``Rather than presenting evidence, [the 
objector] asserts that FDA did not adequately justify its conclusions. 
Such an assertion will not justify a hearing.''). The report also 
attempts to dismiss EPA's conclusions by complaining that EPA's 
assessment fails to include ``any analysis of the relationship between 
RBC AChE and PNS AChE.'' This also, cannot justify a hearing. As has 
been previously noted, FMC, who bears the statutory burden for 
producing such data, has failed to provide data in the PNS that would 
allow EPA to make the suggested comparison (See, 73 FR 42683, 42699, 
July 23, 2008 (hearing denied where NRDC made no evidentiary proffer 
supporting its claim that each of the factors cited in EPA's risk 
assessment ``poses a serious risk of understating the risks''); 70 FR 
21619, April 27, 2005 (objector questioned exposure assessment and 
studies relied on for assessment; hearing denied because no information 
presented); 72 FR 39557, 39560, July 19, 2007 (``Although Public 
Citizen alleged that the studies that FDA evaluated do not support the 
safety of x-rays of 10 MeV or lower used for inspection of cargo 
containers that may contain food, Public Citizen did not present any 
evidence that would have led to a different conclusion concerning the 
safety of the subject additive.'').
    iii. Denial of Objection. EPA's well-established policy when 
evaluating blood cholinesterase inhibition is to use RBC AChE data as 
an indicator of possible effects on AChE in the PNS; EPA adopted this 
policy for a number of reasons (Ref. 76 at 32). EPA's reasoning here is 
straightforward. As a biomarker of exposure, blood AChE inhibition can 
be correlated with the extent of exposure. There is often a direct 
relationship between a greater magnitude of exposure and an increase in 
incidence and severity of clinical signs and symptoms as well as blood 
AChE inhibition. In other words, the greater the exposure, the greater 
the amount of AChE inhibition that will be present in the blood and the 
greater the potential for an adverse effect to occur. RBC measures of 
AChE inhibition also provide: (1) Pharmacokinetic evidence of 
absorption of the pesticide and/or its active metabolite(s) into the 
bloodstream and systemic circulation; and (2) pharmacodynamic evidence 
of binding to AChE, the neural form of the target enzyme. Because the 
interaction with AChE is widely accepted as a key event of the 
mechanism of toxicity for anticholinesterase pesticides, inhibition of 
this AChE in the blood creates the presumption that a chemical also is 
causing inhibition of neural AChE. Chemicals are absorbed into the 
blood and transported to the PNS. Pharmacokinetically, the blood 
compartment and the PNS are ``outside of'' the central nervous system, 
i.e., separated from the CNS by the blood-brain barrier. Thus, RBC 
measures of AChE activity are viewed as a better surrogate for the 
effects on AChE in the peripheral nervous system than are enzyme 
changes in the CNS. Because data on AChE inhibition in the PNS have 
rarely been gathered in animals, blood AChE inhibition measures are 
generally the only information available to assess the potential of 
chemicals to inhibit AChE in the peripheral nervous system.
    Finally, based on the record, FMC seemingly intended in the past 
for RBC AChE to be used as a surrogate for peripheral AChE inhibition. 
In 2005, FMC submitted a time course study with plasma and RBC AChE 
inhibition following acute exposure to carbofuran in adult rats. The 
title of this study is ``The toxicokinetics of peripheral 
cholinesterase inhibition from orally administered carbofuran in adult 
male and female CD rats (Ref. 5).'' Although this study is entitled 
``peripheral cholinesterase inhibition,'' there are no actual measures 
of peripheral toxicity (e.g., liver, lung, heart). Instead, RBC and 
plasma ChEs are the only measures included. That report states that 
``carbofuran reversibly inhibits cholinesterase activity by binding to 
acetycholinesterase in red blood cells * * * Carbamylation of 
cholinesterase after the association of carbofuran leads

[[Page 59642]]

to an accumulation of acetylcholine and inhibition of nerve function at 
the neuronal and neuromuscular synapse.'' Based on this statement, FMC 
assumed at the time of conducting and submitting this study that 
measures of RBC AChE were relevant for predicting neurotoxicity and for 
use in risk assessment. For all of these reasons, the Petitioners' 
objection is denied.
    c. Objection/hearing request subissue: ``Lip-smacking'' as CNS 
effect. Petitioners object that EPA's evidence of ``lip smacking'' in a 
carbofuran adult developmental rat study does not support concern for 
potential PNS effects because lip smacking is more properly correlated 
to CNS, rather than PNS inhibition. In support, the Petitioners proffer 
testimony that relies on four published studies, none of which was 
conducted with carbofuran. The papers describe pharmacological and 
physiological analyses of the bases of ``purposeless chewing 
movements'', ``chewing jaw movements'', ``chewing motions and tongue 
protrusions'', and ``tongue protrusion and gaping'' seen in rats dosed 
with either cholinergic or dopaminergic drugs.
    i. Background. In the proposed rule, in addition to the data in 
pups showing frank PNS effects (tremors), EPA discussed the results of 
another carbofuran study that appeared to be a possible consequence of 
PNS inhibition, to provide further explanation of the basis for EPA's 
concern that carbofuran could cause adverse PNS effects. The proposed 
rule stated that ``[t]here is indication in a toxicity study where 
pregnant rats were exposed to carbofuran that effects on the PNS are of 
concern; specifically, chewing motions or mouth smacking was observed 
in a clear dose-response pattern immediately following dosing each 
day'' (73 FR 44873, July 31, 2008). EPA explained that the California 
Department of Pesticide Regulation calculated a BMD05 and 
BMDL05 of 0.02 and 0.01 mg/kg/day, and established the acute 
PoD based on this study. The Agency also explained that ``[t]hese BMD 
estimates are notable as they are close to the values EPA has 
calculated for brain AChE inhibition and being used as the PoD for 
extrapolating risk to children'' (73 FR 44873, July 31, 2008). The 
similarities of the BMDs in adult and juvenile rats suggests that 
toxicity may be occurring in juvenile animals which cannot be detected 
due to the challenges with assessing clinical signs in juvenile rats.
    The Petitioners did not raise the allegation contained in their 
objections as part of the Petitioners' comments. The context in which 
``lip smacking'' was addressed was a sentence that states, ``One issue 
raised at the FIFRA SAP meeting was whether `lip smacking' observed in 
the adult females in the developmental toxicity study were the result 
of PNS or CNS AChE inhibition'' (Ref. 18 at 82). In a footnote to this 
allegation, the Petitioners stated ``Moreover, it is impossible to tell 
from the study data whether this ``lip smacking'' was a PNS or a CNS 
effect.'' (Ref. 18 at 82). The Petitioners' comments focused instead on 
the contention that the study was irrelevant because the dose levels in 
the study were higher than the dose levels at which EPA was regulating 
for AChE inhibition (Ref. 18 at 82).
    EPA did not respond to the Petitioners' description of the 
discussion at the SAP, since it correctly characterized the discussion. 
However EPA responded fully to the Petitioners' comment regarding the 
dose levels in the final rule and response to comments.
    ii. Denial of hearing request. There can be no legitimate argument 
that this comment raised the issue in sufficient detail to allow 
Petitioners to object that ``lip smacking'' is more properly correlated 
with CNS inhibition, and to supplement the objection with the published 
literature studies they cite here. See, e.g., Forest Guardians v. US 
Forest Service, 495 F.3d 1162, 1170-1172 (10th Cir. 2007) (Claim held 
waived where comments ``failed to present its claims in sufficient 
detail to allow the agency to rectify the alleged violation''); 
National Association of Manufacturers v. US DOI, 134 F.3d 1095, 1111 
(DC Cir. 1998) (``We decline to find that scattered references to the 
services concept in a voluminous record addressing myriad complex 
technical and policy matters suffices to provide an agency like DOI 
with a `fair opportunity' to pass on the issue.'') For the reasons 
discussed in Unit VI.C, EPA considers the objection and evidence 
untimely, and therefore waived. As such, this objection does not 
warrant a hearing.
    But in any event, this issue is not material. EPA's decision to 
retain a 4X children's safety factor did not rest exclusively, or even 
significantly--on the effects observed in this developmental study. 
Rather, EPA retained the children's safety factor based on the lack of 
data in the PNS and/or a surrogate at the low end of the response 
curve, and the fact that the available pup RBC data at higher doses 
affirmatively indicate that the PNS appears to be significantly more 
sensitive than the CNS (73 FR 44871-44872; 74 FR 23073-23075). Indeed, 
it is clear from both the proposed and final rules that the results of 
this study merely supplemented the Agency's bases for concern (73 FR 
44871-44872; 74 FR 23073-23075). The Petitioners' complaint that the 
effects occurred at dose levels three times higher than PoD and 
therefore do not quantitatively support the 4X children's safety factor 
is equally immaterial. The record is clear that EPA relied on 
comparisons between the BMD50 estimated for pup brain and 
RBC AChE inhibition to derive the 4X (73 FR 44871-44872; 74 FR 23073-
23075). A hearing can only be based on a genuine issue of disputed 
fact. Where a party's factual allegations are contradicted by the 
record, there is no genuine dispute (40 CFR 178.32(b)(1)) (See, 73 FR 
42683, 42701 July 23, 2008; 57 FR 6667, 6672, February 27, 1992) (``A 
hearing must be based on reliable evidence, not on mere allegations or 
on information that is inaccurate and contradicted by the record.'').
    iii. Denial of objection. The carbofuran developmental study does 
not definitively resolve whether the effects described were the product 
of PNS or CNS AChE inhibition; because only RBC AChE inhibition data 
were collected it is not possible to determine the degree of CNS 
inhibition. However, as the Petitioners acknowledge, chewing or oral 
fasciculations, which are the movements EPA described at the SAP 
meeting and in the proposed and final rules, have often been reported 
as an early sign of toxicity produced by carbamates and OPs in rats 
(Exhibit 5 at 2). Petitioners also acknowledge that ``oral 
fasciculations'' are indeed a peripheral neuromotor response (Id.) 
(``some of the toxicity is peripherally mediated or an effect on the 
PNS (for example, muscle fasiculations and tremors are due to 
inhibition of AChE at the motor endplate of the muscle)''). 
Nevertheless, Petitioners attempt to confuse the issue by providing 
several different descriptions of oral movements, from lip-smacking to 
mouth smacking to mouth movements to chewing movements, and claiming 
that it is clear that these are all CNS effects. As an initial matter, 
it is unclear whether all of the study authors in Petitioners' cited 
literature are referring to the same phenomenon. It is therefore 
unclear whether the oral movements from the carbofuran developmental 
study (which EPA described as ``lip-smacking'' and ``fasiculations'') 
are the same responses described as ``tongue protrusion,'' ``gaping,'' 
``yawning,'' and ``chewing movements'' in the pharmacology papers 
Petitioners reference. It is not unlikely that all of

[[Page 59643]]

the different papers refer to somewhat different actions; Rupniak et 
al. (Ref. 68) were able to produce ``chewing jaw movements'' by chronic 
treatment with haloperidol, a dopaminergic receptor antagonist, which 
suggests that the movements studied in that paper are not purely 
cholinergic. The fact that anticholinergics could block the 
haloperidol-induced dopaminergic movements shows that this is not a 
straightforward physiological response dealing only with the 
cholinergic system. For the same reason, this calls into question the 
contention that the effects are exclusively CNS-related.
    Similarly, the claim that the ``the masticatory response'' is 
clearly a CNS effect is equally misleading and inaccurate. The report 
in Exhbit 5 claims that ``[t]he masticatory response is considered a 
preliminary index of convulsive activity and convulsions have been 
demonstrated to be caused by changes in brain chemistry.'' None of the 
papers the Petitioners cited describe this ``masticatory response'' in 
that way. Instead, those papers all state that this response is seen at 
relatively low doses of these anticholinesterases. By way of contrast, 
convulsions are seen at high doses. The Exhibit also implies that the 
``masticatory'' response and convulsions are a continuum of the same 
phenomemon; however EPA is aware of no scientific support for this 
claim, and Petitioners have provided none.
    Petitioners' objection on this issue is therefore denied.
    The Exhibit also implies that the ``masticatory'' response and 
convulsions are a continuum of the same phenomemon; however EPA is 
aware of no scientific support for this claim, and Petitioners have 
provided none.
    d. Objection/hearing request subissue: EPA's analysis does not rely 
on Good Laboratory Practice (GLP)-compliant studies. Petitioners object 
that EPA's reliance on the ORD data is problematic because the data 
were not conducted in accordance with EPA's GLP regulations at 40 CFR 
part 160.
    i. Background. The only data available on the effects of carbofuran 
on the pup PNS are RBC AChE inhibition data from two studies conducted 
by EPA-ORD. These data unequivocally show that pup RBC AChE is more 
sensitive than pup brain AChE. EPA also used these data in its 
calculations supporting the 4X children's safety factor. In their 
comments on the proposed rule, Petitioners alleged that, ``the Moser 
study may not meet minimum criteria for scientific acceptability.'' 
They based this on a claim that critical data were unavailable for this 
study, including: A complete protocol, analysis of dosing solutions, 
clinical observations, standardization of brain and RBC AChE results in 
terms of amount per unit of protein, and quality assurance records of 
inspections for the carbofuran portion of the study. However, no more 
specific explanation was provided as how this purportedly missing data 
rendered the data scientifically deficient. EPA responded in full to 
these allegations in the final rule and response to comments document.
    EPA's regulations at 40 CFR part 160 establish a set of principles 
that provides a framework within which laboratory studies are planned, 
performed, monitored, recorded, reported, and archived. GLP helps 
assure EPA that the data submitted are a true reflection of the results 
obtained during the study and can therefore be relied upon when making 
risk/safety assessments. The regulations are applicable only to studies 
that support, or are intended to support applications for ``research or 
marketing permits'' for pesticides regulated under FIFRA (40 CFR 
160.1(a)).
    ii. Denial of hearing request. On several grounds, a hearing on 
this subissue is not warranted. First, this objection fails to identify 
a dispute of material fact. There is no dispute that the EPA-ORD 
studies were not conducted in strict accordance with EPA's GLP 
regulations. Nor have Petitioners identified a substantive flaw in 
those studies that they believe resulted from the lack of compliance 
with the regulations, or otherwise challenged the scientific validity 
of those studies. Thus, the only issue presented is whether EPA should 
rely on otherwise scientifically valid studies that were not conducted 
in accordance with its GLP regulations. This is clearly a legal or 
policy issue. Hearings are not appropriate on such issues; issues of 
fact, not of law or policy are required to justify a hearing (40 CFR 
178.32(b)(1)).
    A further defect is that Petitioners have submitted no evidence on 
this point. In fact, this claim consists of nothing more than the bare 
statement that EPA's analysis does not rely on GLP-compliant studies. A 
hearing will not be granted on ``mere allegations'' or ``general 
contentions'' (40 CFR 178.32(b)(2)). To the extent the Petitioners are 
relying on the information submitted as part of their comments on the 
proposed rule, this does not cure the defect, since no substantiating 
information or other evidence was presented in support of their 
comments. Nor can simple reiteration of a comment made on the proposed 
rule justify a hearing. EPA responded to these comments in the final 
rule, and by ignoring the EPA's final rule on this subissue, 
Petitioners have failed to lodge a relevant objection. Both EPA and FDA 
precedent make clear that when the agency substantively responds to 
comments on the proposal, the commenter may only keep that issue alive 
in its objections by addressing the agency's substantive response. See, 
e.g., 73 FR 42701 (denying hearing because NRDC merely repeated its 
assertion that the study was not representative from its petition, 
rather than objecting to the basis EPA asserted in its petition denial 
for concluding that the study was representative).
    Indeed, this entire objection is not material. The EPA-ORD data are 
the only valid pup RBC data using carbofuran; in the absence of these 
data, EPA would have no data that would provide relevant information on 
carbofuran's effects on children's PNS. Under such circumstances, EPA 
would be required to retain the statutory default 10X, because there 
would be no ``reliable data'' on which to base any other factor.
    iii. Denial of objection. The mere fact that a study is not 
conducted in accordance with EPA's GLP regulations does not mean that 
the study is scientifically invalid, or that EPA is prohibited from 
considering the study. The GLP regulations do not apply to EPA-ORD 
generated data, but rather to studies conducted to ``support 
applications for research or marketing permits for pesticide products'' 
(40 CFR 160.1(a)). Moreover, the regulations establish general 
practices; they do not identify the only good laboratory practices that 
will result in scientifically valid data. Other laboratory protocols, 
such as that used by EPA-ORD are equally valid. In recognition of this 
fact the regulations do not prohibit EPA from considering studies that 
were not conducted in accordance with EPA's GLP regulations, but merely 
provide that EPA may refuse to consider such studies to be ``reliable'' 
(40 CFR 160.17(a)).
    Nor does compliance with EPA's GLP regulations guarantee the 
validity of the study's results. The RBC data from FMC's carbofuran CCA 
studies, which were conducted in accordance with EPA's GLP regulations, 
were unanimously determined to be scientifically invalid by the FIFRA 
SAP (Ref. 36).
    Any claim that the conduct of the EPA-ORD studies raised questions 
as to their scientific validity is equally baseless. EPA's ORD data 
were reviewed by the FIFRA SAP, which concluded that, ``EPA-ORD has 
provided excellent

[[Page 59644]]

data regarding RBC AChE inhibition by carbofuran'' (Ref. 36 at 55).
    As EPA explained in response to the Petitioners' comments, all of 
the information the Petitioners claimed was missing had been previously 
made publically available as part of the SAP review of the carbofuran 
NOIC, and was provided again in response to FMC's FOIA request. A 
complete study protocol, as well as a report of the quality assurance 
(QA), technical, and data reviews of the study, were available, which 
demonstrated that the procedures and documentation are in accordance 
with the National Health and Environmental Effects Laboratory (NHEERL)/
ORD Quality Assurance Management Plan. Concerning standardization of 
brain and RBC AChE in terms of protein concentration, the Agency notes 
that this analysis has not been performed or provided in all the 
studies on the record, including those sponsored by FMC. However, in 
the Moser study (Ref. 56), the AChE activity was standardized in terms 
of tissue weight per ml, so the amount of protein was consistent across 
samples, which is an acceptable and widely used practice. Further, 
abnormal (or ``clinical'') observations were recorded when they 
occurred, although the animals could not be watched while they were in 
the motor activity chambers. Finally, the registrant is correct that 
the dosing solutions for the comparative ChE study were not analyzed, 
but ORD performed this analysis for the adult studies in McDaniel et 
al. (Ref. 54), and the preparation and stability of the carbofuran 
samples were confirmed therein. For these reasons, this objection is 
denied.
    e. Objection/hearing request subissue: Consistency of EPA's 
approach to deriving the carbofuran children's safety factor--i. 
Background. The Petitioners argue that EPA's approach to deriving 
carbofuran's children's safety factor is inconsistent with that 
Agency's approach in deriving the safety factors for other NMC 
chemicals. Specifically, they point to carbaryl, which had a safety 
factor of 1X.
    Petitioners raised this issue in their comments on the proposed 
rule. In the final rule, EPA explained at length, the basis for its 
conclusion that the available data using carbaryl, provided by the 
carbaryl registrant, supported a finding that a 1X children's safety 
factor would be ``safe'' (74 FR 23058 and Ref. 85). EPA explained that 
the different safety factors established for carbaryl and carbofuran 
resulted from differences in the chemicals themselves, as reflected by 
the available data (Id).
    ii. Denial of hearing request. A hearing is not appropriate on this 
objection because it raises a legal or policy claim, rather than a 
dispute as to a material issue of fact. The claim that EPA acted 
inconsistently in assessing different pesticide chemicals is purely a 
legal issue. There is no factual dispute that EPA established a 
children's safety factor of 1X for carbaryl, and a safety factor of 4X 
for carbofuran. The only dispute concerns whether EPA's basis for 
distinguishing between the two is reasonable, and this is a legal 
claim, on which a hearing is not appropriate (40 CFR 178.32(b)(1)).
    In addition, the Petitioners make no claim other than to reiterate 
the allegation made in their comments on the proposed rule, that EPA's 
assessment of carbofuran is inconsistent with its assessment of 
carbaryl. Consequently, Petitioners' objection on this subissue is 
irrelevant, and therefore immaterial, with regard to EPA's final 
tolerance revocation regulation because Petitioners ignored EPA's 
extensive analysis of this issue in the final rule and refiled their 
comments on the proposal as if EPA's determination in the final rule 
did not exist. By ignoring the EPA's final rule on this subissue, 
Petitioners have failed to lodge a relevant objection. Nor have they 
proffered any evidence in support of this claim. When EPA responds to a 
comment in the final rule, mere reiteration of the comment in 
objections does not present a live controversy unless the objector 
proffers some evidence calling EPA's objection into question (See, 
e.g., 73 FR 42700-42701).
    iii. Denial of objection. Carbaryl was evaluated no differently 
than carbofuran. The different children's safety factors applied to 
each chemical reflects the differences in the chemicals themselves, as 
reflected by the data.
    It is typical EPA practice to use the central estimate on the BMD 
as an appropriate measure for comparing chemical potency and the lower 
limit on the central estimate (i.e., BMDL) as an appropriate measure 
for extrapolating risk. In the case of carbaryl, the Petitioners 
inappropriately focused on the BMDL10, instead of the 
BMD10. The more appropriate comparison is between the 
BMD10; the carbaryl brain BMD10 is 1.46 mg/kg 
compared with the RBC BMD10 of 1.11 mg/kg. As such, the 
brain to RBC ratio is 1.3X. Therefore, for carbaryl, the brain and RBC 
AChE data are similarly sensitive. When the tissues are similarly 
sensitive, the Agency prefers to use data from the target tissue (i.e., 
central or peripheral nervous system) rather than data from a surrogate 
tissue (i.e., RBC). EPA's hazard identification for carbaryl states:

    ``Although the RBC BMDL10 for the more sensitive PND 
11 rat is numerically the lowest (0.8 mg/kg) of the two 
compartments, biologically the RBC BMDL10 is similar to 
the brain BMDL10 (1.1 mg/kg). Since the brain is the 
target tissue for the NMCs, and the brain BMDL10 1.1 mg/
kg is also protective of the surrogate and often more variable RBC 
ChE measurements (BMDL10 0.8 mg/kg), then the brain 
BMDL10 of 1.1 mg/kg is the appropriate PoD for both 
children and adults in the carbaryl risk assessment (Ref. 82).''

Thus, for carbaryl, biologically the RBC and brain AChE inhibition were 
basically equivalent where brain AChE inhibition is a direct measure in 
a target tissue and RBC AChE inhibition is used as a surrogate for the 
peripheral nervous system. This is quite different from the situation 
with carbofuran where a significant difference was noted between RBC 
and brain AChE inhibition, showing that RBC AChE inhibition (used as a 
surrogate for the PNS) is more sensitive.
    The approach used for carbaryl--i.e., relying on the central 
estimate for purposes of comparison across age groups, and using 
biological compartments and the lower limits for use as PoDs--is being 
used by EPA in its carbofuran risk assessment. In addition, this 
approach was used in the NMC cumulative risk assessments (CRA) and 
single chemical risk assessments for multiple OPs. Thus, the Agency is, 
in fact, being consistent in its hazard identifications among the AChE-
inhibiting pesticides.
    With regard to the carbaryl children's safety factor, the available 
brain and RBC dose-response data in PND11 pups include data from the 
lower end of the dose-response curves. ORD's comparative ChE data with 
carbaryl show that at the lowest dose at or near 20% inhibition in 
brain and RBC AChE were observed. Although not ideal, the carbaryl data 
provide information closer to the benchmark response of 10%, and 
therefore allow for a reasonable estimation of the BMD10 and 
BMDL10. This is distinctly different from ORD's data with 
carbofuran in PND11 and PND17 pups where the 50% or greater RBC AChE 
inhibition was observed at the lowest dose. Accordingly, the objection 
is denied.
    2. EPA's Mathematical Modeling Underlying the Calculation of a 4X 
Children's Safety Factor. Petitioners argue that EPA committed numerous 
errors in calculating the 4X children's safety factor. First, 
Petitioners allege that, even assuming that RBC values are relevant, 
EPA's conclusion that the RBC-related effects in the relevant

[[Page 59645]]

studies were four times more sensitive than brain effects is not 
mathematically supportable. Referencing statistical analyses performed 
by a contractor, they claim that ``[a]t most, the data support a 2X 
safety factor, based on actual difference between brain and RBC 
(ranging between 1 and 1.9).''
    Second, the Petitioners claim that there are several technical 
errors in the way EPA conducted the statistical modeling that formed 
the quantitative support for the 4X children's safety factor. They also 
object that the mathematical assumptions underlying EPA's modeling are 
not justified and fail to support the 4X children's safety factor. In 
this regard, they allege that EPA's children's safety factor was based 
on calculations that (i) are not based on ``within animal 
comparisons;'' (ii) have been applied incorrectly and inconsistently to 
the data, which exaggerated the difference; (iii) overstate the 
evidence for higher relative RBC sensitivity; and (iv) treated 
carbofuran inconsistently as compared to other NMCs. They claim that by 
removing the inconsistencies from EPA's data, the data yield a brain/
RBC ratio of 1.3, which confirms Petitioners' approach. These five 
allegations are addressed separately below.
    In support of these claims, the Petitioners offer allegations on 
the points above, referencing two memoranda from Drs. R. Sielken and C. 
Valdez-Flores (Exhibits 7, 8, 9) that generally describe and summarize 
the analyses and modeling they conducted. The full analyses underlying 
these memoranda were not included with the objections.
a. Objection/Hearing Request Subissue: Use of Within-Animal Brain to 
RBC Inhibition Comparisons To Derive the Children's Safety Factor
    i. Background. In the proposed rule, EPA explained its approach to 
deriving an alternate to the default 10X children's safety factor. This 
safety factor was calculated using the ratio of RBC and brain AChE 
inhibition, using the data on administered dose for the PND11 animals 
from the EPA-ORD studies and the FMC studies combined. In other words, 
EPA estimated the BMD50 for PND11 animals for RBC and brain 
from each quality study and used the ratio from the combined analysis, 
resulting in a BMD50 ratio of 4.1X. EPA estimated the RBC to 
brain potency ratio using EPA's data for RBC (the only reliable RBC 
data in PND11 animals for carbofuran) and all available data in PND11 
animals for brain. EPA's approach yields a ratio of about 4 fold.
    EPA also compared the BMD50 ratios for PND17 pups (who 
are slightly less sensitive than 11-day olds) in the EPA-ORD study, to 
confirm that the observed differences in sensitivity between RBC and 
brain were not unique to the PND11 data. The result of EPA's modeling 
showed a BMD50 ratio of 3.3 \13\ between brain and RBC in 
the PND17 pups.
---------------------------------------------------------------------------

    \13\ EPA corrected a technical error identified in Petitioners' 
comments, which resulted in a revised ratio of 2.6X, for the final 
rule.
---------------------------------------------------------------------------

    In their comments on the proposed rule, Petitioners presented 
essentially the same arguments raised in this objection. They argued 
that a more plausible and straightforward approach would be to compare 
the RBC and brain AChE levels at the same time in the same rat when 
these rats are exposed to carbofuran. The comments claimed that a 
statistical evaluation of the experimental data on AChE inhibitions in 
RBC and brain in rats due to carbofuran exposure had been performed by 
Sielken & Associates, which showed that the percentage inhibition of 
RBC AChE in a rat is almost the same as the percentage inhibition of 
brain AChE in the rat. Although the results of the statistical analyses 
were summarized in the comments, the underlying analyses were not 
submitted.
    In the final rule, EPA provided a detailed explanation of its 
rationale for rejecting the Petitioners' approach (74 FR 23055; Ref. 
85).
    ii. Denial of hearing request. EPA is denying Petitioners' request 
for a hearing on this objection for two reasons. First, as in its 
comments, Petitioners failed to submit the underlying modeling 
conducted in support of its assertions. Petitioners' consultant merely 
asserts that the results are as presented in his summarized testimony. 
In the absence of the underlying scientific analyses, these are 
effectively no more than mere allegations or general contentions. 
Hearings will not be granted on this basis alone. (40 CFR 178.32(b)(2); 
see also 73 FR 42702 (July 23, 2008)(denying NRDC's hearing request on 
objection that EPA's risk assessment was inadequate because EPA lacked 
data on how pest strips were used in their homes, because ``NRDC 
provided no factual information to support its claim''); 68 FR 46403, 
46406-46407 (August 5, 2003) (FDA denied a hearing involving a 
challenge to FDA's reliance on consumption pattern data because the 
objector ``did not present any specific information to dispute P & G's 
consumption pattern data; instead, [objector] simply asserted that 
other consumption patterns were likely.''); accord Community Nutrition 
Institute v. Novitch, 773 F.2d 1356, 1363 (DC Cir. 1985) (``Mere 
differences in the weight or credence given to particular scientific 
studies * * * are insufficient [to show a material issue of fact for a 
hearing].'')).
    Second, Petitioners' hearing request is inadequate because they do 
not object to the basis EPA asserted in the final rule for rejecting 
this approach. Specifically, Petitioners do not challenge EPA's 
conclusion that their suggested approach is fundamentally flawed in 
several regards, nor proffer evidence in support of that challenge. 
Petitioners also do not challenge EPA's analyses, showing that the 
results of their suggested approach are in fact consistent with EPA's 
conclusions. As a consequence, Petitioners' objections are irrelevant, 
and therefore immaterial, with regard to EPA's final tolerance 
revocation regulation. The statute, however, requires that objections 
be filed on the final rule not the proposal. By ignoring the EPA's 
final rule on this subissue, Petitioners have failed to lodge a 
relevant objection. Prior FDA decisions under its regulations are 
instructive here. Objections and hearing requests were filed in 
response to a food additive regulation covering the irradiation of 
poultry. (62 FR 64102 (December 3, 1997)). The objector argued that the 
addition of an anti-oxidant (ethoxyquin) to irradiated chicken prior to 
the chicken's use in animal feeding studies compromised the studies 
because the ethoxyquin would have decreased the level of lipid 
peroxides in the chicken to levels found in chicken that had not been 
irradiated. The FDA noted, however, that it had considered the question 
of ethoxyquin's effect on lipid peroxide levels in the final rule and 
determined that while ethoxyquin can retard the normal oxidation of 
chicken fat to peroxides, ethoxyquin cannot reverse oxidation that has 
already occurred. FDA denied the hearing request reasoning that because 
the objector did ``not dispute FDA's explanation in the final rule as 
to why addition of ethoxyquin did not compromise the CIVO studies, and 
provided no information that would have altered the agency's conclusion 
on this issue * * * there is no factual issue that can be resolved by 
available and specifically identified reliable evidence'' (62 FR 
64105). See also 53 FR 53176, 53191 (December 30, 1988) (FDA denied a 
hearing request noting that given FDA's prior conclusion that the 
studies relied upon by the objector were unreliable, the ``burden 
shifted to [the objector] to maintain the viability of its

[[Page 59646]]

objection by proffering some information that called into question the 
agency's conclusion on this matter.'')). Similarly, here, Petitioners 
have not challenged the basis EPA asserted for rejecting their 
suggested within-animal analyses, nor have they proffered any 
information calling into question EPA's conclusion.
    iii. Denial of objection. EPA notes that the Petitioners 
recommended this approach of comparing the degree of inhibition for 
each animal as part of their presentation to the carbofuran SAP. EPA 
also addressed this approach, comparing RBC to brain in the same 
animals, at the SAP and in the responses to the SAP report (Ref. 83). 
It is notable that the SAP did not endorse this approach (Id.).
    EPA's analyses of the Petitioners' approach identified several 
significant deficiencies. First, the comparison suggested by the 
Petitioners would require that EPA ignore existing data. This is 
because only EPA's study of PND 11 animals contains both brain and RBC 
data, so the comparisons suggested by the commenter can only be made 
using that dataset. However, the dose levels in that study were so high 
that the lower portion of the dose-response curve was missed. At these 
higher doses, there is little difference between the levels of brain 
and RBC inhibition. This phenomenon--i.e., that the relative 
sensitivity of RBC compared to brain appears smaller at higher doses--
is also shown in multiple chlorpyrifos studies where blood or 
peripheral measures of AChE inhibition are more sensitive than brain at 
low to mid doses, but the tissues appear to be similar at higher doses.
    Second, the Petitioners' approach is fundamentally flawed. The 
Petitioners' suggested alternative relies exclusively on comparisons 
between the degree of inhibition in the treated animals without any 
regard to the doses at which the effects occurred. For example, one 
animal may have shown, on average, 10% inhibition in the brain, when it 
demonstrated 20% RBC inhibition. Under this approach, what would be 
relevant would simply be the ratio of 1:2. But the Agency believes it 
is critical to focus on the ratios of potency, which is the ratio of 
the doses in the data that cause the same level of AChE inhibition. The 
Agency's approach of comparing potencies is more directly relevant for 
regulatory purposes than comparisons of average inhibition. This is 
because dose corresponds more directly to potential exposures, which is 
what EPA regulates (i.e., how much pesticide residue does a child 
ingest). By comparison, the Petitioners' suggested reliance purely on 
the average degree of inhibition provides no information that 
corresponds to a practical basis for regulation.
    Finally, the range of ratios of effects that the Petitioners 
propose as an alternative is consistent with range of potencies that 
EPA has calculated at these higher doses, so the Petitioners' results 
do not ultimately contradict EPA's assessment, which is intended to 
account for the effects at lower doses. Briefly, if the dose-responses 
for RBC and brain inhibition were linear, ratios of inhibition would 
equal ratios of BMDs. However, these dose-responses are not at all 
linear; rather the available data demonstrate that brain and blood 
dose-responses have somewhat different shapes. Thus, estimates of 
relative effects at particular, relatively high, doses will not 
determine the estimated ratios at lower doses. This is because the 
dose-response curves begin to level off as they reach maximal 
inhibition (i.e., no more inhibition is possible), so, at high doses, 
there is almost no difference between the ratio of brain and RBC 
inhibitions. Except at the lowest dose, which produced 50% AChE 
inhibition, where the ratio is slightly greater than 2, the remaining 
ratios are only slightly greater than 1. Given the inevitable 
statistical noise in these measures, it is clear that the ratios 
expected from EPA's modeling are substantially similar to the results 
the Petitioner finds in its comparison between individuals. 
Accordingly, the Petitioners' suggested comparisons at higher doses 
provide no evidence of what occurs at lower doses; and thus provides no 
evidence that demonstrates that EPA's modeling results at lower doses 
is inaccurate.
    b. Objection/hearing request sub issue: Scientific validity of 
EPA's approach. The Petitioners object that EPA's approach has not been 
established as scientifically valid. They claim that data for other 
carbamates suggests that BMD50 s for the carbamates tend to 
diverge more than the dose levels used to select the PoD (i.e., the 
BMD10 s). In addition, they criticize EPA's approach for 
incorrectly assuming that the relationship between BMD50 s 
and BMD10 s is linear, which they claim overstates the 
potential differences. They claim that these issues could be avoided by 
adopting their suggested approach of using within-animal comparisons to 
determine the relative sensitivity of RBC and brain AChE. The evidence 
submitted in support of this subissue is the summary presented in the 
objection.
    i. Background. In the proposed rule, EPA explained that its 
comparisons of the BMD50 s for brain and blood relied on an 
assumption that the magnitude of the difference between RBC and brain 
AChE inhibition is constant across dose. In other words, EPA assumed 
that the RBC and brain AChE dose curves are parallel, even though there 
are no data to test this assumption (73 FR 44873). In their comments, 
the Petitioners criticized EPA for this assumption, and recommended 
using ``within animal comparisons'' to avoid having to make this 
assumption. In the final rule, EPA explained that its decision to rely 
on comparisons of BMD50 s rather than BMD10 s was 
because the RBC data for 10% inhibition levels was insufficient to 
allow the Agency to generate the necessary estimates. EPA agreed that 
the dose-response curves were not parallel at these lower doses, (i.e., 
that the relationship between BMD50 s and BMD10 s 
was not linear) but that EPA lacked any data that would allow it to 
make any other assumption. EPA nevertheless rejected the Petitioners' 
suggested approach of relying on within-animal comparisons, because, as 
described in the preceding objection, it is intrinsically flawed and 
scientifically invalid.
    ii. Denial of hearing request. A hearing on this subissue is not 
appropriate because Petitioners' request is based on mere allegations, 
general contentions, and speculation (40 CFR 178.32(b)(2)). No evidence 
has been submitted on any of the issues raised in this objection. 
Petitioners have provided no evidence that supports their assertion 
that EPA's assumption that the dose-response curves will remain 
parallel at lower doses overestimates the ratios. In the absence of 
data at the low end of the dose-response curve, which Petitioners were 
required to have developed, there is just as great a likelihood that 
EPA's assumption underestimates the ratios. Petitioners have not cited 
to any data from other carbamates to support their contention that 
BMD50 s tend to diverge more than BMD10 s; the 
objection fails to even identify the carbamate chemicals that 
purportedly support this claim. Further, the claim is untimely, as it 
was not raised as part of their comments on the proposed rule. For the 
reasons discussed in Unit VI.D, EPA will not consider such information 
in support of a request to justify a hearing.
    In addition, a hearing on this objection is denied on the ground of 
materiality (40 CFR 178.32(b)(1)). In the absence of EPA's assumption, 
EPA would have no basis for deriving an alternate children's safety 
factor. Thus, EPA would have to raise the children's safety factor from 
4X to the statutory

[[Page 59647]]

default of 10X, rather than to lower the factor as the Petitioners 
seek. As discussed at length in the preceding objection subissue, the 
Petitioners' suggested alternative of within-animal comparisons is 
scientifically invalid, and provides no useful basis for regulatory 
action. Accordingly, if Petitioners establish that available 
information does not support EPA's assumption that the dose-response 
curves are parallel, then EPA is left with no valid scientific 
information to determine the correct dose-response curve at lower 
doses, or to establish a BMD10 (21 U.S.C. 346a(b)(2)(C)). 
Because deviation from a 10X children's safety factor requires some 
``reliable data'' on the shape of the dose response curve for RBC AChE, 
Petitioners' objection on EPA's low dose-response curve assumptions, in 
combination with the failure to provide a valid alternate approach 
would result in a higher children's safety factor, and a conclusion 
that EPA has underestimated carbofuran's risks.
    iii. Denial of objection. EPA disagrees that its approach is not 
scientifically valid. The models used to develop the BMD estimates have 
been repeatedly reviewed and approved by the SAP (Refs. 34, 35). The 
most recent occasion was the February 2008 carbofuran SAP, which 
concluded that ``[t]he dose-response analysis done by the Agency for 
the EPA-ORD PND11 study was appropriate and led to a very uncertain 
BMD10 * * * This [assumed dose-response] curve fit well in 
the region where there were data, but there was no way to validate it 
at low doses'' (Ref. 36 at 54).
    EPA acknowledges that it lacks information to confirm its 
assumption that the dose-response curves remain parallel at lower 
doses. EPA believes this is the most reasonable assumption, given the 
absence of information at low doses, since it neither presumes that RBC 
inhibition will increase or decrease at lower doses. Contrary to 
Petitioners' naked assertion that EPA's approach overestimates the 
difference, there is no inherent reason to expect that EPA's assumption 
would overestimate or underestimate the difference between 
BMD50 s and BMD10 s. If indeed data were to show 
that EPA's assumption overestimated the difference--and Petitioners 
have submitted none--it would only be as a result of the animal 
biology, as there is no indication in the mathematical modeling that it 
overestimates the difference in any way. The mathematical relationship 
between BMD50 s and BMD10 s certainly provides no 
hint that there might be a bias. In this regard, it is notable that the 
February 2008 SAP concluded that `[w]hat the Panel observed at the low 
end [of the dose-response curve] made it tempting to assume linearity 
at this part of the dose-response curve'' (Ref. 36 at 55).
    Regarding the Petitioners' claim that data for other carbamates 
suggests that BMD50 s for the carbamates tend to diverge 
more than the dose levels used to select the PoD (i.e., the 
BMD10 s). EPA cannot confirm the accuracy of this 
allegation, as Petitioners have provided neither data nor any 
explanation of a biological basis to support this claim. Nor is EPA 
able to substantiate this claim based on the information currently 
available. However, there is no a priori reason to expect such a 
systematic divergence between ratios of BMD50's and ratios 
of BMD10 s for blood and brain, based either on biology or 
the mathematical relationship between BMD50's and 
BMD10 s. It is actually far more probable that the variation 
from chemical to chemical (due both to real variation among chemicals 
and to statistical sampling noise) would be large enough to make a 
conclusive determination from data difficult.
    c. Objection/hearing request sub issue: Combining data from 
different toxicological studies--i. Background. In its risk assessment, 
EPA relied on all of the valid data from the available studies to 
calculate the estimates that served as the PoD, and to calculate the 
estimates of BMD50 s that serves as quantitative support for 
derivation of the 4X children's safety factor.
    For purposes of the PoD, the Agency used a meta-analysis that 
combined valid data from all available studies to calculate the 
BMD10 and BMDL10 for pups and adults; this 
analysis includes brain data from studies where either adult or 
juvenile rats or both were exposed to a single oral dose of carbofuran. 
The quality brain AChE data from the three studies (2 FMC, 1 EPA-ORD) 
conducted with PND11 rats, in combination, provides data to describe 
both low and high doses. By combining the three studies in PND11 
animals together in a meta-analysis, the entire dose-response range is 
covered.
    EPA also combined studies in calculating the 4X children's safety 
factor. EPA derived the ratio of RBC and brain AChE inhibition using 
the data on administered dose for the PND11 animals from the EPA-ORD 
studies and the FMC studies combined. In other words, EPA estimated the 
BMD50 for PND11 animals for RBC and brain from each quality 
study and used the ratio from the combined analysis, resulting in a 
BMD50 ratio of 4.1X. EPA estimated the RBC to brain potency 
ratio using EPA's data for RBC (the only reliable RBC data in PND11 
animals for carbofuran) and all available data in PND11 animals for 
brain.
    In their comments on the proposed rule, Petitioners claimed that 
EPA's decision to combine data for different strains of rats, sexes, 
experiments, laboratories, dates, dose preparations, rat ages, and 
times between dosing and AChE measurement, is problematic, claiming 
that these differences in study design severely limit the validity of 
EPA's comparisons. Further, they alleged that differences in data and 
methods EPA used to estimate its BMD50 (brain) and 
BMD50 (RBC) caused EPA to overestimate the difference 
between brain and RBC, and thereby invalidating any comparison of the 
estimates. Specifically, Petitioners were concerned that the datasets 
from the six studies EPA used for brain differ not only because they 
were from different studies, but also because the data were taken at 
different times ranging from 15 minutes to 4 hours after dosing.
    EPA responded to these comments in full during the rulemaking (74 
FR 23055-23057 (May 14, 2009); Ref. 85). Petitioners referenced these 
comments in their objections, but presented no further argument or 
evidence on any of these points. Because Petitioners originally raised 
this claim also with respect to the derivation of EPA's PoD, even 
though they only raise it in this objection here, the Agency responds 
to both points below.
    ii. Denial of hearing request. The Petitioners have not met the 
requirements for a hearing on this subissue. Petitioners have not 
challenged the basis EPA asserted for rejecting their suggested within-
animal analyses, and have therefore failed to lodge a relevant 
objection. Both EPA and FDA precedent make clear that when the agency 
substantively responds to comments on the proposal, the commenter may 
only keep that issue alive in its objections by addressing the agency's 
substantive response (40 CFR 178.32(b)(3)). Nor have they proffered any 
evidence that calls the substance of EPA's conclusions into question. A 
hearing is not warranted on the basis of mere denials or contentions 
(40 CFR 178.32(b)(2)). See 73 FR 42698-42699 (When an objector does not 
challenge EPA conclusions in the section 408(d)(4)(iii) order but 
rather challenges some prior conclusion that was superseded by the 
section 408(d)(4)(iii) order, the objector has not raised a live 
controversy as to an issue material to the section 408(d)(4)(iii) 
order); 53 FR 53176, 53191 (December 30, 1988) (FDA denied a hearing 
request noting that given FDA's prior conclusion that the

[[Page 59648]]

studies relied upon by the objector were unreliable, the ``burden 
shifted to [the objector] to maintain the viability of its objection by 
proffering some information that called into question the agency's 
conclusion on this matter.'')).
    Second, this objection is not material. In the case of carbofuran, 
EPA used a sophisticated analysis of multiple studies and datasets to 
develop the PoD for the carbofuran risk assessment. Instead of this 
analysis, EPA could simply have followed the general approach laid out 
in its BMD policy (Ref. 100), which is used in the majority of risk 
assessments. Under this general approach, EPA would regulate using the 
most sensitive effect, study, and/or dataset. If the Agency chose not 
to combine the data in its analyses, as the commenters' suggested, data 
collected at or near the peak time of effect (i.e., 30 minutes) would 
in fact provide the more relevant datasets. If this more simple 
approach were taken, in accordance with BMD guidance, EPA would select 
the lowest BMDL10. Assuming the commenters' values were 
used, EPA would have selected a PoD of 0.009 mg/kg/day, instead of the 
0.03 mg/kg/day that EPA is currently using in its risk assessment. A 
lower PoD of 0.009 mg/kg/day would significantly increase carbofuran's 
level of estimated risk.
    iii. Denial of objection. In general, EPA believes that 
consideration of all available data is the scientifically more 
defensible approach, rather than the selective exclusion of reliable 
data. The Agency's Draft BMD Guidance says the following: ``Data sets 
that are statistically and biologically compatible may be combined 
prior to dose response modeling, resulting in increased confidence, 
both statistical and biological, in the calculated BMD'' (Ref. 76). The 
SAP has reviewed and approved EPA's practice of combining data from 
studies numerous times (Refs. 34, 35, 36). Most recently, as part of 
the carbofuran SAP, the SAP was fully aware that the Agency was 
planning to derive BMD estimates from data sets using different strains 
of rats (Ref. 36). Accordingly, the Agency's carbofuran analysis has 
included all available, valid data in its analysis.
    By contrast, the Petitioners' suggested analysis ignores relevant, 
scientifically valid data. Their analysis left out the 30-minute data 
from MRID no. 47143705 (Ref. 2), but provided no rationale as to why it 
would be appropriate to selectively exclude data from the time frame in 
this study most relevant to the risk assessment (i.e., peak AChE 
inhibition). The Petitioners' analysis of the individual datasets from 
this study showed that at 30 minutes the females and males provide 
BMDL10 s of 0.009 mg/kg/day and 0.014 mg/kg/day, 
respectively. When the datasets were combined, inclusion of the 30-
minute timepoint from MRID no. 47143705 decreased the BMDL10 
from 0.033 mg/kg/day to 0.030 mg/kg/day.
    Although the Petitioners complain that EPA's approach of combining 
data across multiple studies is scientifically inappropriate, the 
Petitioners themselves combined the results of analysis from four 
datasets in the information presented with their comments and 
referenced in their objections. Indeed, it is notable that most of the 
criticisms raised by the Petitioners also apply equally to the 
Petitioners' own analysis, as described in more detail in EPA's 
Response to Comments document (Ref. 85).
    The Petitioners are also incorrect that differences in the data 
available for brain and RBC are so great as to invalidate comparisons 
of the BMD estimates. EPA used all the data available in each case, and 
used a hierarchical model to account for variability of the BMD among 
laboratories for the brain endpoint, which the SAP has explicitly 
reviewed and approved numerous times (Refs. 34, 35, 36).
    The Petitioners are correct that data from both sexes were combined 
for brain but only male data were used for RBC. However, EPA first 
performed an evaluation of the differences between the sexes. EPA 
combined data from males and females only after showing that they did 
not respond differently.\14\ The only remaining study to examine AChE 
activity in RBC in PND11 animals, after FMC's flawed studies were 
eliminated, contained only male animals. Both BMD50 s for 
brain and RBC in adults were based on 15 minutes, the minimum time 
interval after dosing when a sample was taken, in each dataset.\15\ 
This is also true for the brain endpoint in PND11 animals. However, the 
only study available of the RBC endpoint in PND11 animals was conducted 
at 40 minutes after dosing, and did not include a recovery time course 
study.
---------------------------------------------------------------------------

    \14\ See pp. 34-35 in the brain document dated October 25, 2007 
for adults, pp. 47-48 in the same document for PND11 animals; p. 15 
in the RBC document dated October 23 for adults.
    \15\ See Oct. 5, 2007 reports, page 8 (for the values of the 
time interval) and page 63 (setting the parameter delta to the 
minimum non-zero value for that interval) in the RBC report, and 
page 9, and page 45 for the corresponding report for Brain.
---------------------------------------------------------------------------

    EPA believes that its decision to combine data for purposes of its 
BMD50 estimates supporting the children's safety factor is 
equally appropriate, and any differences in the way in which the 
studies were conducted did not impact the validity of EPA's analyses. 
For example, one of Petitioners' complaints was that it was 
inappropriate to combine studies because the data in the studies were 
taken at different times, ranging from 15 minutes to 4 hours after 
doses. EPA responded to the allegation that this was problematic by 
conducting the analysis that the Petitioners claimed should have been 
done to support this. As explained in the final rule, although EPA 
disagreed with the Petitioners' contention that this was necessary or 
appropriate, EPA conducted the Petitioners' suggested analysis, and 
used the dose-time-response model to extrapolate BMD50 s to 
develop a common point of comparison between all studies. Specifically, 
EPA extrapolated the PND11 brain analysis to estimate BMD50 
for 40 minutes after dosing for comparison with the existing PND11 RBC 
BMD50, and extrapolated the PND11 RBC BMD50 to 15 
minutes after dosing for a range of assumed recovery half-lives, for 
comparison to the existing PND11 brain BMD50. The results 
are provided in (Refs. 24, 25). In either approach, the estimate of the 
RBC to brain potency ratio in PND11 animals is increased, and EPA's 
safety factor would correspondingly increase to reflect that larger 
difference. For example, when the PND11 brain BMD50 is 
extrapolated to 40 minutes, the RBC to brain potency ratio grows to 4.7 
(Ref. 24 at 46), and when the PND11 RBC BMD50 is 
extrapolated to 15 minutes, using a range of estimates for the recovery 
half-life of the RBC endpoint, the RBC to brain potency ratio ranges 
from 4.2 to 4.6 (Ref. 24). The Petitioners' approach would therefore 
support a children's safety factor of 5X rather than the 4X EPA is 
currently applying in its risk assessments. Nevertheless, EPA continues 
to believe that its current use of a 4X factor reflects the most 
reliable interpretation of existing quality data.
    Although it is true that EPA's BMD50 for brain was based 
on data from 6 datasets while the RBC BMD50 was based on a 
single study, this is because scientifically acceptable RBC data are 
only available from a single study. As discussed, the fact that EPA 
used all available data sets in its modeling does not affect the 
validity of its modeling (Ref. 76).
    For all of the foregoing reasons, this objection is denied.
    d. Objection/hearing request sub issue: Technical Flaws in EPA's 
statistical comparisons. In their objections, Petitioners claim to have 
found a number of technical errors and inconsistencies in how the 
modeling

[[Page 59649]]

was conducted. Correcting for these errors, they claim, shows that the 
BMDs for brain and RBC data are essentially the same, which was 
consistent with the results of modeling conducted by the Petitioners 
when evaluating the individual animal data. Specifically, Petitioners 
allege that the approach EPA used to estimate BMD50 s for 
carbofuran is inconsistent with its ``meta-analysis'' approach of 
combining studies. The Petitioners also argued that EPA's modeling 
failed to account for significant difference in study methodologies 
(e.g., time to sacrifice following dosing). For example, EPA's 
BMD50 (Brain) is calculated at 15 minutes after exposure 
starts whereas EPA's BMD50 (RBC) is calculated at 40 minutes 
after exposure starts. EPA's BMD50 (brain) is based on 6 
studies whereas EPA's BMD50 (RBC) is based on 1 study, and 
the dose-time-response modeling methodology for combined studies and 
EPA's BMD50 (brain) is different than the dose-time response 
modeling methodology for a single study and EPA's BMD50 
(RBC). Petitioners also allege that EPA applied its dose-time-response 
model inconsistently between the brain and RBC calculations, alleging 
that the power was fixed to 1.00 for brain, but estimated for RBC.'' 
They also criticize the modeling on the grounds that EPA did not: (1) 
Account for differences between the combined datasets; (2) develop a 
protocol supporting its approach; (3) clearly document its method; (4) 
accurately document model parameters; (5) rely on a plausible dose-
response model, or (6) report its data accurately or transparently. 
They further allege that ``removing all of these inconsistencies in 
methodology results in a ratio of 1.3, which corresponds with the ratio 
that the Petitioners claim to have obtained based on their within 
animal comparisons.
    Petitioners have provided neither further details of their concerns 
than the explanation above, nor any other evidence to support this 
objection.
    i. Background. EPA addressed all of the commenters' claimed 
inconsistencies in its final rule and Response to Comments document (74 
FR 23055-23056; Ref. 85 at 61-62). For the majority of these claimed 
flaws and inconsistencies, EPA explained that the Petitioners had 
misunderstood EPA's analyses, or that the Petitioners' were incorrect. 
However in response to certain allegations, EPA conducted new analyses 
to determine whether the suggested alternative approaches would make 
any significant difference in EPA's modeling outcomes.
    Petitioners have provided little detail in their objections on the 
issues they intend to raise in their testimony; in most instances, they 
simply allege that EPA's modeling was incorrect. But as the objections 
reference the Petitioners' comments on the proposed rule, EPA assumes 
that they intend to raise only the points previously discussed in their 
comments.
    ii. Denial of hearing request. The Petitioners' request for a 
hearing on the issues raised in this objection is denied on two bases. 
First, Petitioners have not challenged the substance of EPA's response 
to their comments or submitted evidence that calls the substance of 
EPA's conclusions into question. As previously explained, their failure 
to challenge the actual basis of EPA's final rule affects the 
materiality of the objection and hearing request (40 CFR 178.32(b)(3)). 
See 73 FR 42698-42699 (When an objector does not challenge EPA 
conclusions in the section 408(d)(4)(iii) order but rather challenges 
some prior conclusion that was superseded by the section 408(d)(4)(iii) 
order, the objector has not raised a live controversy as to an issue 
material to the section 408(d)(4)(iii) order) 53 FR 53176, 53191 
(December 30, 1988) (FDA denied a hearing request noting that given 
FDA's prior conclusion that the studies relied upon by the objector 
were unreliable, the ``burden shifted to [the objector] to maintain the 
viability of its objection by proffering some information that called 
into question the agency's conclusion on this matter.'')). Further, 
Petitioners have not rebutted, or even acknowledged, the additional 
analyses EPA undertook at their suggestion, and discussed in the final 
rule, which ultimately provided further support for EPA's position. For 
example, in response to the complaint that EPA should have generated a 
new dose-response model in order to calculate the BMD50 s 
for brain and RBC, EPA conducted the suggested calculation, and under 
that analysis, the result is the same as that EPA originally 
calculated. Similarly, in response to the complaint that EPA should 
have used the dose-time-response model to extrapolate BMD50 
s to develop a common point of comparison between all studies, EPA 
conducted that analysis and described it in the final rule (74 FR 
23055-23056 (May 15, 2009)). The result of this reanalysis supported a 
higher children's safety factor than EPA's 4X. But rather than 
challenge the new analysis, Petitioners simply repeat the assertions 
made in their comments. Because the objections on these points fail to 
account for EPA's analyses, the objections are contradicted by the 
record, and accordingly, fail to demonstrate a factual dispute (40 CFR 
178.32(b)(1)). See 73 FR 42698-42699 (Denying NRDC hearing where 
objection reiterated claims premised on conclusions in EPA's 
preliminary risk assessment, rather than objecting to EPA's conclusions 
in the revised assessment prepared for the petition denial); 49 FR 6672 
(February 22, 1984) (no hearing if claim based on demonstrably false 
premise); 57 FR 6667 (February 27, 1992) (``A hearing must be based on 
reliable evidence, not on mere allegations or on information that is 
inaccurate and contradicted by the record'').
    Second, as in their comments, Petitioners failed to submit the 
underlying modeling they claim to have conducted in support of their 
objections. Petitioners' consultants merely assert that the results are 
as presented in their summarized testimony. In the absence of the 
underlying scientific analyses, these are effectively no more than mere 
allegation or general contentions. Hearings will not be granted on this 
basis. (40 CFR 178.32(b)(2); see also 68 FR 46403, 46406-46407 (August 
5, 2003) (FDA denied a hearing involving a challenge to FDA's reliance 
on consumption pattern data because the objector ``did not present any 
specific information to dispute P & G's consumption pattern data; 
instead, [objector] simply asserted that other consumption patterns 
were likely.''); accord Community Nutrition Institute v. Novitch, 773 
F.2d 1356, 1363 (DC Cir. 1985) (``Mere differences in the weight or 
credence given to particular scientific studies * * * are insufficient 
[to show a material issue of fact for a hearing].'').
    iii. Denial of Objection. For all of the reasons discussed in the 
final rule and Response to Comments documents, this objection is 
denied. A summary of EPA's bases, which were discussed in detail in 
both the final rule and Response to Comments document, is presented 
below.
    Consistency of EPA approach. In their comments, the Petitioners' 
explained that the alleged inconsistency with which they were concerned 
was that ``EPA attempts to extrapolate a BMD10 to a 
BMD50 without refitting the data. That is, EPA uses the 
dose-response model obtained for the BMD10 rather than 
obtaining a new model for BMD50.'' They claimed this was 
``especially troublesome since EPA has expressly stated that the model 
obtained for BMD10 (RBC) is unreliable.''

[[Page 59650]]

    The Petitioners' allegation on this point is incorrect. The model 
itself does not need to change in order to develop a BMD50. 
Whether one wants to estimate the BMD10 or the 
BMD50, one would use the same underlying model. EPA simply 
developed a mathematical expression to adjust parameter values for that 
fitted model so that, for any given benchmark response level (in 
particular, for 10% or 50% inhibition), the corresponding BMD could be 
estimated as a parameter in that model. The same expression makes it 
possible to compute a BMD for any given response level from estimates 
based on any other response level. Mathematically, it is not necessary 
to refit the model to the data to estimate different BMD levels.
    However in response to the comments, EPA conducted their suggested 
calculation, and the ratio of brain to RBC BMD50 s in this 
new analysis is the same as the ratio EPA calculated by using the 
mathematical expression (Refs. 24, 25). Both provide a ratio of brain 
to RBCs BMD50 of 4X. Specifically, in the just cited 
documents above, the values are for PND11 brain BMD50 are 
0.35 (Ref. 24 at 40) and for RBC, 0.086 (Ref. 25 at 20), resulting in a 
ratio of 4.09.
    With regard to the EPA's purported statement that the 
BMD10 model is unreliable, the Petitioners misconstrued 
EPA's statement. EPA stated that it cannot reliably estimate the RBC 
BMD10 and BMDL10 in pups because it lacks data at 
low doses, not because its model is unreliable. Given the greater 
amount of data, the estimate for the BMD50 is substantially 
better supported, and thus, less uncertain, than the estimate of the 
BMD10.
    Differences in study methodologies. Both BMD50 s for 
brain and RBC in adults were based on 15 minutes, the minimum time 
interval after dosing when a sample was taken, in each dataset.\16\ 
This is also true for the brain endpoint in PND11 animals. However, the 
only study available of the RBC endpoint in PND11 animals was conducted 
at 40 minutes after dosing, and did not include a recovery time course 
study.
---------------------------------------------------------------------------

    \16\ See Oct. 5, 2007 reports, page 8 (for the values of the 
time interval) and page 63 (setting the parameter delta to the 
minimum non-zero value for that interval) in the RBC report, and 
page 9, and page 45 for the corresponding report for Brain.
---------------------------------------------------------------------------

    As noted in the previous objection response, EPA used the dose-
time-response model to extrapolate BMD50 s to develop a 
common point of comparison between all studies. Using that approach 
would support a children's safety factor of 5X rather than the 4X EPA 
has applied.
    Although it is true that EPA's BMD50 for brain was based 
on data from 6 datasets while the RBC BMD50 was based on a 
single study, this is because scientifically acceptable RBC data are 
only available from a single study. As discussed in the preceding 
objection response, the fact that EPA used all available data sets in 
its modeling does not affect the validity of its modeling (Ref. 76).
    Inconsistent application of model. EPA did not apply its model 
inconsistently; the difference to which the Petitioners refers results 
from the differences between the available data. In order to generate 
an estimate of the power parameter, data at both extremes of the dose-
response curve are necessary. Despite the comparatively greater amount 
of brain inhibition data, the brain data did not provide information at 
both extremes of the curve. A value of 1.00 is the standard default in 
this situation for all the NMC dose-response analyses. Moreover, 
despite the limited information at the extremes of the dose-response 
curve for estimating power in the brain data, a power parameter of 1.00 
is consistent with the available brain data. By contrast, because the 
available RBC data provides the necessary information at higher doses, 
the power in the RBC data could be directly estimated and was 
significantly less than 1.0.
    EPA is unable to comment on the analyses referenced in the 
Petitioners' objections as they failed to provide them. However, EPA 
has previously explained the reasons for rejecting the suggested 
analysis based on brain RBC comparisons within the same animal. This is 
discussed at length in the final rule and response to comments, as well 
as Unit VI.E.2.a of this Order.
    f. Objection/hearing request sub issue: Consistency in approach 
between carbofuran and other NMC chemicals--i. Background. In their 
comments on the proposed rule, the Petitioners argued that EPA's 
approach to deriving carbofuran's children's safety factor was 
inconsistent with its approach to deriving the safety factors for other 
NMC pesticides. They identified only three specific chemicals: 
Aldicarb, oxamyl, and carbaryl. With respect to aldicarb they argued 
that although the relative potency of carbofuran is less than aldicarb, 
the uncertainty factors assigned by EPA presuppose that carbofuran is 
ten times more toxic that aldicarb. They claim that the aldicarb data 
show that by all objective measures of toxicity, aldicarb is nearly 
twice as acutely toxic as carbofuran across all species tested. They 
further claim that an alternative approach to relative rankings of 
carbamates proposed by the SAP in its assessment of the NMCs (which 
also considered the rate of recovery) also showed aldicarb having 
approximately twice the potency of carbofuran. They further alleged 
that the children's safety factor for carbaryl was inconsistent with 
the safety factor applied to carbofuran. Finally, the Petitioners 
compared the aPAD, aRfD, and uncertainty factors for oxamyl, aldicarb, 
and carbaryl, concluding that these were inconsistent with EPA's 
conclusions for carbofuran.
    EPA responded to these comments in both the final rule and the 
accompanying response to comments document (74 FR 23058 (May 15, 
2009)).
    In their objections, Petitioners have not identified any specific 
facts that they believe demonstrate inconsistency. They merely allege 
that the ``relative potency of carbofuran as compared to other N-methyl 
carbamates does not correspond with OPP's aPAD for carbofuran relative 
to those same compounds.''
    ii. Denial of hearing request. A hearing is denied on this subissue 
because there is no disputed factual matter for resolution at a 
hearing. There is no dispute concerning the children's safety factors 
that EPA applied to the other carbamates, nor how EPA derived those 
safety factors. Thus, the only question is whether it was reasonable 
for EPA to account for the fact that other chemicals had a greater 
amount of toxicity data, and therefore greater uncertainty, in 
determining the appropriate children's safety factor, when the statute 
requires EPA to account for ``the completeness of the data'' (21 U.S.C. 
346a(b)(2)(C)). This question requires the application of a legal 
standard to undisputed facts. Hearings are not appropriate on questions 
of law or policy (40 CFR 178.32(b)(1)). See, 73 FR 42706-42707) 
(denying NRDC hearing request when the only question raised was whether 
a human study using only adult males met the regulatory requirement of 
``scientifically valid and relevant data''. FDA has repeatedly 
confirmed that the application of a legal standard to undisputed facts 
is a question of law for which a hearing is not required. (See, e.g., 
68 FR 46403, 46406 n.18, 46408, 46409 (August 5, 2003) (whether facts 
in the record show there is a reasonable certainty of no harm is a 
question of law; whether a particular effect is a ``harm'' is a 
question of law)).
    In addition, Petitioners have not challenged the substance of EPA's 
response to their comments, but simply reiterated their comments on the 
proposed rule. Accordingly, a hearing is

[[Page 59651]]

not warranted, as the objection is subissue is irrelevant, and 
therefore immaterial, with regard to EPA's final tolerance revocation 
regulation (40 CFR 178.32(b)(3)). See 73 FR 42698-42699 (July 23, 2008) 
(When an objector does not challenge EPA conclusions in the section 
408(d)(4)(iii) order but rather challenges some prior conclusion that 
was superseded by the section 408(d)(4)(iii) order, the objector has 
not raised a live controversy as to an issue material to the section 
408(d)(4)(iii) order; 53 FR 53176, 53191 (December 30, 1988) (where FDA 
responds to a comment in the final rule, repetition of the comment in 
objections does not present a live controversy unless the objector 
proffers some evidence calling FDA's conclusion into question)).
    Nor have they submitted evidence that calls the substance of EPA's 
conclusions into question. Petitioner's entire argument concerning this 
issue is a single conclusory sentence. A hearing will not be granted on 
``mere allegations'' or ``general contentions.'' (40 CFR 178.32(b)(2)) 
(See 53 FR 53176, 53199 (December 30, 1998)) (``Rather than presenting 
evidence, [the objector] asserts that FDA did not adequately justify 
its conclusions. Such an assertion will not justify a hearing.'').
    iii. Denial of objection. Although it is unclear which precise 
chemicals the Petitioners believe demonstrate that EPA was 
inconsistent, the only ones on which any allegations were arguably 
presented were those identified in their comments on the proposed rule: 
aldicarb, carbaryl, and oxamyl. Accordingly, EPA denies this objection 
for the same reasons that EPA explained in its final rule and comment 
responses.
    In their comments, the Petitioners provided information on the oral 
LD50 in rat and the BMDL10 for AChE in rat brain 
or human RBC. The comments also provided uncertainty factors for the 
three NMCs, the respective aRfD \17\ or aPAD \18\ and the cumulative 
risk assessment oral potency factor. The LD50 and 
BMDL10, values provided are not completely accurate.
---------------------------------------------------------------------------

    \17\ aRfD is the acute reference dose.
    \18\ aPAD is the acute RfD adjusted for the Children's Safety 
Factor.
---------------------------------------------------------------------------

    The allegations and the supporting information contained in 
Petitioners' comments were inaccurate. For example, the LD50 
values in the oxamyl RED were 3.1 mg/kg (male) and 2.5 mg/kg (female), 
rather than 30 mg/kg as the Petitioners claimed. Further, the Agency's 
recent hazard assessments of carbaryl and aldicarb are each consistent 
with EPA policies and practice, as well as with the Agency's approach 
to the assessment of carbofuran.
    The Petitioners' assertions regarding aldicarb were based on an 
earlier assessment. At the time the Agency conducted the assessment to 
which the commenters refer, the Agency was unaware of the difference in 
sensitivity between PND17 and PND11 animals. Since EPA became aware of 
the differences, EPA has required the aldicarb registrant to conduct a 
CCA study in PND11 rats; the Agency anticipates the receipt of this 
study and the companion range-finding and time course studies in 2009. 
In the absence of these data, EPA will apply the statutory default 
children's safety factor to account for the additional sensitivity of 
PND11 animals, because the Agency lacks any ``reliable data'' that 
could be used to derive a reduced factor that EPA could determine will 
be ``safe for infants and children.''
    With regard to the carbaryl children's safety factor, the available 
brain and RBC dose-response data in PND11 pups include data from the 
lower end of the dose-response curves. ORD's comparative AChE data with 
carbaryl show that at the lowest dose 20% or near 20% inhibition in 
brain and RBC AChE was observed. Although not ideal, the carbaryl data 
provide information closer to the benchmark response of 10%, which 
allows for a reasonable estimation of the BMD10 and 
BMDL10. This is distinctly different from ORD's data with 
carbofuran in PND11 and PND17 pups where 50% or greater RBC AChE 
inhibition was observed at the lowest dose.
    Petitioners' other comparisons are equally inapposite. The 
LD50, BMDL10, and relative potency factor from 
the cumulative risk assessment are each measures of chemical potency. 
Thus, these calculations provide reasonable comparisons of the relative 
potency of aldicarb, carbofuran, and oxamyl. However, the Petitioners' 
allegations were based on comparisons of the aPAD, aRfD, and 
uncertainty factors, which are not measures of potency and should not 
be interpreted as such (Ref. 79). The magnitude of the uncertainty 
factors is intended to account for uncertainty in the available data 
for a particular chemical. For example, it is standard practice to 
apply a 10X uncertainty factor for extrapolation from animals to humans 
when ethically and scientifically sound human data are not available 
for the pesticide of interest. And this explains the difference in the 
uncertainty factors applied to the three chemicals. Deliberate dosing 
studies in human subjects conducted with aldicarb and oxamyl were 
reviewed and accepted by the HSRB for both scientific validity and 
ethical conduct. This is not the case for carbofuran. As discussed 
below in Unit VI.G, the HSRB concluded that the carbofuran study was 
not sufficiently scientifically robust for use in the risk assessment. 
Therefore, there is less uncertainty in the aldicarb and oxamyl risk 
assessments since quality data are available in humans and the 
interspecies factor can be reduced or removed for these chemicals. 
There are no comparable data for carbofuran.
    Accordingly, this objection is denied.
    F. Objections to EPA's Drinking Water Exposure Assessments.
    Petitioners raise separate objections to EPA's estimates of 
drinking water exposures from contaminated ground water and to the 
estimates from contaminated surface water. In each objection, 
Petitioners argue that, based on newly proposed restrictions submitted 
as part of their objections, the exposure estimates will be 
significantly lower than EPA's estimates in the final rule.
    1. Objections relating to groundwater exposure estimates. 
Petitioners raise several challenges to the ground water concentration 
estimates in the final rule. They allege that EPA's estimates are not 
based on the best available data, but on obsolete data and overly 
conservative assumptions that are inappropriate because use has been 
prohibited in all areas like those seen in these data. The objection 
also claims that the requirements in the new registration proposals to 
require setbacks from all drinking water wells ranging between 100 and 
1,000 feet will ensure that all potential groundwater exposures will be 
below the level of concern. In support of this objection three analyses 
were submitted in Exhibits 12, 13, and 14.
    a. Objection/hearing request subissue: Reliance on the results of 
the prospective ground water study (PGW) and historical monitoring to 
validate groundwater exposure estimates. The Petitioners object that 
EPA should not have relied for validation on their PGW study or 
historical monitoring data. They argue that these data are from a 
period when use was an ``order of magnitude greater.'' Additionally 
they allege that all areas like those seen in the PGW have now been 
removed from the carbofuran label, and so the study results do not 
accurately reflect current risks. In support of this objection, 
Petitioners reference their comments on the proposed rule, and Exhibit 
12.
    i. Background. In the proposed rule, EPA relied on a drinking water 
assessment that used both monitoring data for carbofuran and modeling

[[Page 59652]]

methods (Refs. 13, 42, 44, 47, 67). Regarding the potential exposure 
from contaminated groundwater, the Agency concluded that drinking water 
taken from shallow wells is highly vulnerable to contamination in areas 
where carbofuran is used around sandy, highly acidic soil, although 
sites that are less vulnerable (e.g., deeper aquifer, higher organic 
matter) could still be prone to have concentration exceeding acceptable 
exposures. EPA concluded that the results of its modeling were 
consistent with the results of the available monitoring data, including 
a PGW study conducted by FMC in the 1980s, when scaled to reflect the 
current lower rates of application (73 FR 44881).
    In their comments, the Petitioners complained that EPA's reliance 
on the PGW was inappropriate because that study no longer reflected 
current conditions. Petitioners also summarized the results of their 
``National Leaching Assessment'' which used PRZM and ``databases 
specifically created to provide access to all necessary inputs for a 
national scale PRZM modeling.'' They claimed that after accounting for 
the use prohibitions on their September 2008 label, the maximum 1-in-10 
year peak concentrations in all potential carbofuran use areas is 1.2-
1.3 ppb, while expected concentrations in most areas covered by this 
assessment are below 1.0 ppb. Neither the ``National Leaching 
Assessment'' nor the ``National Pesticide Assessment Tool'' upon which 
the assessment appears to have been based, were submitted to EPA as 
part of the Petitioners' comments.
    In the final rule, EPA revised the assessment conducted for the 
proposed rule in response to the FMC comments submitted during the 
comment period, which requested cancellation of the use on a number of 
crops and imposed a number of restrictions intended to address the 
potential for groundwater contamination. These restrictions included 
use prohibitions in certain states, and well setbacks. Taking these 
into account, ground water concentrations were estimated for all 
remaining crops on carbofuran labels, using two new Tier 2 scenarios. 
Based on a new corn scenario in Wisconsin, representative of 
potentially vulnerable areas in the upper Midwest where use remained, 
EPA estimated one-in-ten year concentrations for ground water source 
drinking water of 16 to 1.6 x 10-3 ppb, for pH 6.5 and 7, 
respectively. Well setback prohibitions of 50 ft were proposed on the 
new label for the flowable and granular formulations in select counties 
in Kentucky (7 counties), Louisiana (1 county), Minnesota (1 county), 
and Tennessee (1 county). Analysis of the impact of these setbacks for 
the use on corn indicated that the setbacks would not reduce 
concentrations significantly at locations where exposure to carbofuran 
in ground water is of concern because at acid pHs, carbofuran does not 
degrade sufficiently during the travel time from the application site 
to the well to substantially reduce the concentration.
    EPA concluded that the results of the revised corn modeling were 
consistent with the PGW. Using higher use rates than currently 
permitted, the peak concentration measured in the PGW study was 65 ppb; 
when scaled to current use rates, the estimated peak concentration was 
11 ppb. The final rule explained that EPA's modeling is also consistent 
with a number of other targeted groundwater studies conducted in the 
1980s showing that high concentrations of carbofuran can occur in 
vulnerable areas; the results of these studies as well as the PGW study 
are summarized in References 13 and 67 (74 FR 23079).
    ii. Denial of hearing request. For this hearing request, the 
Petitioners have failed to proffer evidence, which would, if 
established, resolve a material issue in their favor. First, 
Petitioners' evidentiary proffer does not support their contention, and 
consequently, EPA is unable to conclude that there is a reasonable 
possibility that the issue could be resolved in its favor (40 CFR 
178.32(b)(2)). Petitioners' own experts relied on the PGW to validate 
the modeling submitted in support of this objection and to demonstrate 
the safety of the tolerances. The Executive Summary of the National 
Carbofuran Leaching Assessment states

    ``[a] model validation study was conducted in which the results 
of a prospective groundwater monitoring (PGW) study conducted for 
cabofuran in Maryland from 1981-1983 were compared to the model 
simulations that most closely matched the PGW study site in terms of 
location, soil texture, organic carbon content, and pH. The annual 
peak concentrations during the simulation are on the order of 9 to 
11 ppb, which are similar to the measured concentrations in the PGW 
study (9 to 10 ppb after adjusting for application rate). The 
validation provides context that the model predictions are 
reasonable.''

(Exhibit 12 at 7). See, e.g., 57 FR 33244 (July 27, 1992) (Studies 
cited by NRDC do not provide a basis for the hearing because they 
``support the [FDA] conclusion in question.'').
    Second, this objection is premised on inaccurate factual statements 
that are directly contradicted by the record. For example, the 
objection disregards the fact that EPA scaled the PGW modeling to 
reflect the lower current use rates. The Petitioners present no 
challenge to the methods EPA used to scale the study results; indeed, 
it is likely that their contractor used the same or similar 
methodology. Equally, the objection that EPA relied on ``historical 
monitoring data from a period when carbofuran use was an order of 
magnitude larger'' is simply incorrect (Ref. Obj at 40). The monitoring 
results EPA cited in the final rule were from the 1980s, but the 
targeted monitoring studies were conducted with the same or lower use 
rates as those permitted under the current labeling (74 FR 23085, May 
15, 2009). Such a submission is insufficient to justify a hearing (See, 
73 FR 42696 (July 23, 2008)(denying hearing where objector incorrectly 
claimed that EPA had failed to rely on DDVP-specific information in 
making its children's safety factor determination); 57 FR 6667 
(February 27, 1992) (``A hearing must be based on reliable evidence, 
not on mere allegations or on information that is inaccurate and 
contradicted by the record.'')
    Further, the Petitioners' misrepresentation of EPA's analyses also 
affects the materiality of the hearing request (40 CFR 178.32(b)(3)). 
Even if Petitioners were able to successfully refute the validity of 
the PGW study, it would not affect the validity of the additional 
monitoring data cited in the final rule (74 FR 23079 (May 15, 2009)), 
on which EPA also relied to validate its monitoring. See, 49 FR 6672 
(February 22, 1984) (challenge to one of five related studies; in the 
absence of any additional data bearing on the clinical study, the 
objection constitutes nothing more than an allegation).
    Finally, the evidentiary proffered with respect to the Petitioners' 
allegation that all areas with conditions similar to those found in the 
PGW have been removed from the label is insufficient to warrant a 
hearing (40 CFR 178.32(b)(2)). To the extent this allegation is based 
on the information presented as part of the 2008 comments, this claim 
was rebutted in EPA's final rule, by the modeling based on the 
Wisconsin corn scenario, and by the lack of any underlying analyses to 
support of Petitioners' comments. As explained in the final rule, the 
information provided is insufficient to allow EPA to confirm the 
Petitioners' contention that there is no overlap between use and all 
potentially vulnerable ground water (74 FR 23061-23062 (May 15, 2009)).
    The evidence submitted along with this objection does not cure this 
defect. The only evidence proffered in this regard is the Petitioners' 
comments on

[[Page 59653]]

the proposed rule, and the new analysis submitted in Exhibit 12. As 
previously discussed, mere reiteration of comments made in response to 
the proposed rule does not provide an adequate basis for a hearing, 
unless the objector proffers some evidence calling EPA's conclusion 
into question. Consequently, Petitioners' submission on this issue is 
irrelevant and therefore immaterial, with regard to EPA's final 
tolerance revocation (40 CFR 178.32(b)(3)). The analysis in Exhibit 12 
appears to be the National Leaching Assessment described in 
Petitioners' comments, but modified to account for the proposed 
amendments submitted as part of the objections. As noted previously, 
neither the National Leaching Assessment nor the model on which it was 
based was submitted as part of the comments. Because the National 
Leaching Assessment was available during the comment period but was 
withheld, this information is considered to be untimely and the 
Petitioners have waived the right to rely on it. For the reasons 
discussed in Unit VI.D, EPA therefore will not consider it as an 
appropriate basis for justifying a hearing on its final rule. See 73 FR 
42683, 42696 (July 23, 2008); 72 FR 39318, 39324 (July 18, 2007). 
Further, for the reasons discussed in Unit VI.C, EPA has determined 
that objections and hearing requests based on the newly proposed 
amendments, as well as evidence or analyses premised on those 
amendments, are irrelevant, and therefore immaterial, to EPA's 
determination in the May 15, 2009 final rule that the carbofuran 
tolerances were unsafe and could not be sustained under FFDCA section 
408. Petitioners are actually not objecting to the conclusions in EPA's 
final rule; rather, they are suggesting that EPA might reach a 
different result in a different factual scenario. Objections, however, 
must be directed ``with particularity [at] the provisions of the 
regulation or order deemed objectionable'' (21 U.S.C. 346a(g)(2)).
    iii. Denial of objection. EPA denies this objection on several 
bases. Based on the information available, and even accounting for the 
September 2008 geographic restrictions, the Agency cannot confirm the 
Petitioners' claim that use has been prohibited in all areas with 
conditions similar to the PGW study. Based on the information that was 
timely submitted, the only information provided was in map format. 
While maps are useful for interpreting results, maps alone are 
insufficient for a thorough evaluation of the Petitioners' claim, in 
part because of the maps' spatial resolution. The maps submitted were 
all on a nation-wide scale, which does not provide the level of detail 
necessary to verify the combination of paramaters (e.g., soil textures, 
pH) at locations identified as vulnerable. Further, the maps provided 
by the Petitioner do not represent all carbofuran use patterns. For 
example, Figure IV-2 on page 42 of the Petitioners' comments does not 
address the granular use patterns and proposed label prohibitions. In 
addition, as a general matter, none of the previously submitted 
assessments provided a comprehensive analysis of the distribution of 
soil and water pHs for the Midwest, Northwest or any other region of 
the country where carbofuran use would be permitted on the September 
2008 label, or have the Petitioners provided such an analysis with 
their objections.
    Further, the available scientific information does not support 
their contentions. EPA examined readily available data with respect to 
ground water and soil pH in order to evaluate the spatial variability 
of pH. Data from the USGS and other readily available sources do not 
necessarily encompass the entire range of ground water pH values 
present within a state. This is especially true for shallow ground 
water systems, where local conditions can greatly affect the quality 
and characteristics of the water. Also, pH in a water body can be 
higher or lower than the tabulated average values. In addition, average 
ground water pH values for a given area do not truly characterize the 
area's temporal and especially spatial heterogeneity. This can be seen 
by comparing differences in pH values between counties within a state, 
and by the fact that even within a county individual wells will 
consistently yield ground water with either above- or below-average pH 
values for that county. The ground water simulations in Reference 84, 
Appendix I reflect variability in pH by modeling carbofuran leaching in 
four different soil and subsurface pH conditions (pH 5.25, 6.5, 7.0, 
and 8.7), representing the range in the aquifer system in that area. 
This range also approximates the pH range of natural waters in general. 
The results of the ground water simulations for corn use showed that a 
relatively small (0.5) decrease in pH from 7 to 6.5 resulted in an 
increase in the 1-in-10-year peak concentrations of carbofuran in 
ground water of 4 orders of magnitude.
    The results of EPA's revised corn modeling, based on a new scenario 
in Wisconsin, are consistent with the results of the PGW study 
developed by the registrant in Maryland in the early 1980s. Using 
higher use rates than currently permitted, the peak concentration 
measured in the PGW study was 65 ppb; when scaled to current use rates, 
the estimated peak concentration was 11 ppb. EPA's modeling is also 
consistent with a number of other targeted ground water studies 
conducted in the 1980s showing that high concentrations of carbofuran 
can occur in vulnerable areas; the results of these studies as well as 
the PGW study are summarized in References 13 and 67. For example, a 
study in Manitoba, Canada assessed the movement of carbofuran into tile 
drains and ground water from the application of liquid carbofuran to 
potato and corn fields. The application rates ranged between 0.44-0.58 
pounds a.i./acre, and the soils at the site included fine sand, loamy 
fine sand, and silt loam, with pH ranging between 6.5-8.3. 
Concentrations of carbofuran in ground water samples ranged between 0 
(non-detect) and 158 ppb, with a mean of 40 ppb (Refs. 13 and 67).
    Finally, as discussed above, to the extent this objection relies on 
untimely information and analyses, and on the newly submitted 
registration amendments, the objection is denied as irrelevant and 
immaterial.
    b. Objection/hearing request subissue: Accounting for FMC's label 
mitigation measures. Petitioners object that EPA's risk assessment 
relies on ``unrealistic and overly conservative assumptions about 
potential concentrations,'' and fails to account for FMC's label 
mitigation measures. They claim that maximum concentrations of 
carbofuran in groundwater are expected to be below 1.1 ppb, based on 
the new proposed geographic restrictions and well setbacks. They allege 
that, ``only permeable soils (e.g., greater than 90% sand and less than 
1% organic matter) with acidic soils and water conditions, and shallow 
water tables (e.g., less than 30 feet) are vulnerable to carbofuran 
applications.'' They also claim that vulnerable groundwater only exists 
along eastern seaboard, and in select counties in the United States, 
where use has already been prohibited. They argue that further 
confirmation is provided by the available NAWQA data, which show that 
detections of carbofuran are rare, and occur only at low levels except 
in areas where use is now prohibited. Finally, Petitioners allege that 
in the specific regions where carbofuran will continue to be used under 
the revised label, groundwater pH data collected under the USGS NAWQA 
program demonstrate that the average pH is approximately 7.25, and in 
most regions, moving two standard deviations

[[Page 59654]]

away from average, which they claim would capture 95% of all observed 
values, results in pHs that are still greater than 6.0. According to 
the Petitioners, under such conditions the combination of hydrolysis 
and drinking water well setbacks would ensure that any carbofuran that 
might reach ground water sources would degrade to only de minimis 
concentrations less than or equal to 1.1 ppb.
    In support of this objection, Petitioners cite the analyses 
submitted as part of their comments, and the new analyses in Exhibits 
12, 13, and 14. Exhibits 12 and 13 contain the revised modeling of the 
estimated groundwater concentrations from carbofuran use, based on the 
label restrictions proposed as part of the objections. Exhibit 14 
consists of a statistical summary of groundwater pH statistics from the 
USGS NAWQA database. Means, standard deviations, and numbers of 
groundwater measurements in the database are summarized by state and 
land use within each state.
    i. Background. In the proposed rule EPA concluded that drinking 
water taken from shallow wells is highly vulnerable to contamination in 
areas where carbofuran is used around sandy, acidic soil, although 
sites that are less vulnerable (e.g., deeper groundwater, less coarsely 
textured soils) could still be prone to have concentrations exceeding 
acceptable exposures (73 FR 44881-44883 (July 31, 2008)). EPA also 
described the available NAWQA monitoring data, and explained the 
reasons that the monitoring data tends to underestimate exposure for 
acute risks, such as those carbofuran presents, and so are not 
sufficiently robust to be used as an input into a quantitative risk 
assessment or to serve as a lower bound (73 FR 44880-44881 (July 31, 
2008)).
    As part of their comments on the proposed rule, FMC requested that 
EPA amend their registration to include a number of geographic use 
restrictions and migitation measures intended to address the risks to 
groundwater. In their comments, Petitioners claimed that 
``[g]roundwater sources are vulnerable to carbofuran leaching only 
under certain conditions, namely where permeable soils (e.g., areas 
with soils greater than 90% sand and less than 1% organic matter), 
acidic soil and water conditions, and shallow water tables predominate 
(e.g., where ground water is less than 30 feet).'' The commenters 
claimed that these conditions are rare in areas where carbofuran would 
be used under the new label proposed as part of their comments. They 
further asserted that in ``most states where carbofuran is used, less 
than 2% of the entire surface areas possess sandy soil texture'' and 
that ``low pH conditions are not found in carbofuran use areas allowed 
under the registrant's amended label'' (Ref. 18 at 33-34). They 
described, but did not submit analyses they claimed to have conducted 
to demonstrate this. The summary consisted primarily of maps depicting 
areas identified as vulnerable.
    On December 24, 2008, FMC again requested that EPA amend their 
registration to include additional restrictions intended to further 
mitigate carbofuran's risks to groundwater.
    In response to the September 2008 proposed label restrictions 
submitted as part of the comments, EPA revised its risk assessment to 
take into account the new geographic restrictions, as well as the 
proposed risk mitigation measures. Based on its revised assessment, EPA 
explained in the final rule that it disagreed that the criteria on the 
September 2008 label defined 100% of the conditions where ground water 
sources would be vulnerable to carbofuran leaching. EPA noted that no 
comprehensive analysis had been provided that evaluated how the 
Petitioners had reached this conclusion. As discussed in greater detail 
in EPA's Response to Comments, the information provided as part of the 
Petitioners' comments--primarily maps depicting areas identified as 
vulnerable--was not sufficient to allow the Agency to evaluate their 
claim (Ref. 84).
    EPA also disagreed that the commenters provided sufficient 
information to support their general claim that only high pH conditions 
(pH above 7) existed in all the areas in which carbofuran could be used 
under FMC's September 2008 revised label. EPA presented its assessment 
of the newly submitted label in its Response to Comments document and 
these issues were addressed in substantial detail there (Ref. 84).
    EPA did not evaluate the mitigation measures proposed in the 
December 24, 2008 submission. The mitigation measures in that 
submission were incorporated into the measures proposed by the 
Petitioners as part of their objections on June 30, 2009.
    ii. Denial of hearing request. EPA is denying the hearing requested 
on this objection because, in large measure, if not entirely, it rests 
on the newly submitted mitigation measures accompanying Petitioners' 
objections. As discussed in Unit VI.C, EPA has determined that these 
objections do not warrant a hearing because they are irrelevant, and 
therefore immaterial, to EPA's determination in the May 15, 2009 final 
rule that the carbofuran tolerances were unsafe and could not be 
sustained under FFDCA section 408 (40 CFR 178.32(b)(3)). Petitioners 
are actually not objecting to the conclusions in EPA's final rule; 
rather, they are suggesting that EPA might reach a different result in 
a different factual scenario. Objections, however, must be directed 
``with particularity [at] the provisions of the regulation or order 
deemed objectionable'' (21 U.S.C. 346a(g)(2)). In addition, for the 
reasons discussed in Unit VI.D, EPA has determined that the new risk 
mitigation measures are not appropriately considered at this stage of 
the administrative process, and will not grant a hearing on this basis.
    Petitioners' objections provide no further clarification as to what 
is meant by their claim that EPA's assessment relied on ``unrealistic 
and overly conservative assumptions.'' Therefore, this objection, and 
the attendant hearing request, is denied based on Petitioners' failure 
to state with ``particularity * * * the basis for the objection * * *'' 
(40 CFR 178.25(a)(2)). As Petitioners raised similar allegations in 
their comments, EPA has assumed that they intended to incorporate all 
of the issues raised in the comments on the proposed rule.
    To the extent this objection relies on the September 2008 
mitigation measures, EPA denies the hearing request because the 
evidentiary proffer in support of this objection is insufficient to 
warrant a hearing. The record is clear on its face that EPA did account 
for the mitigation measures in its revised risk assessment supporting 
the final rule. A hearing can only be based on a genuine issue of 
disputed fact (40 CFR 178.32(b)(1)). Where a party's factual 
allegations are contradicted by the record, there is no genuine dispute 
(73 FR 42701-42702 (July 23, 2008) (Denying NRDC's hearing request 
where EPA had revised its residential exposure assessment to address 
the issue complained of); 57 FR 6667, 6668 (February 27, 1992) (``A 
hearing must be based on reliable evidence, not on mere allegations or 
on information that is inaccurate and contradicted by the record.'')).
    The objection also suffers from a further defect; many of the 
allegations in this objection merely reiterate points Petitioners had 
raised in their earlier comments. For example, EPA addressed the claim 
that the NAWQA data from 1993-2006 rarely show detections of 
carbofuran, and that in ``almost every instance'' the observed 
concentrations are low. EPA also addressed the claim that only areas 
with permeable soils (e.g., areas with soils greater than 90% sand and 
less than 1% organic matter), acidic soil and water conditions, and

[[Page 59655]]

where shallow water tables predominate (e.g., where ground water is 
less than 30 feet) present significant risks of leaching. As previously 
discussed, mere reiteration of comments made in response to the 
proposed rule does not provide an adequate basis for a hearing, unless 
the objector proffers some evidence calling EPA's conclusion into 
question (40 CFR 178.32(b)(3)). See, e.g, 73 FR 42701-42702 (July 23, 
2008); 53 FR 53176 (December 30, 1988).
    The evidence submitted in Exhibits 12-14 does not cure these 
defects. As a preliminary matter, much of this evidence is untimely. 
The analyses in Exhibits 12 and 13 appear to be the National Leaching 
Assessment described in Petitioners' comments, but modified to account 
for the proposed amendments submitted as part of the objections. As 
noted previously, neither the National Leaching Assessment nor the 
model on which it was based was submitted as part of the comments. 
Certainly, there is no justification for Petitioners' refusal to 
provide the analyses that were available during the comment period. 
Because the National Leaching Assessment was available during the 
comment period but was withheld, this information is considered to be 
untimely and the Petitioners have waived the right to rely on it. 
Accordingly, as discussed in Unit VI.D, because this evidence was not 
presented as part of the Petitioners' comments, EPA considers that the 
evidence submitted in support of this objection is not appropriately 
considered as a basis for justifying a hearing on the final rule. See 
73 FR 42683, 42696 (July 23, 2008); 72 FR 39318, 39324 (July 18, 2007). 
And in the absence of this evidence, this portion of the objection 
consists of mere allegations and denials, which do not warrant a 
hearing (40 CFR 178.32(b)(2)).
    But even assuming that the evidence was appropriately considered, 
the evidence is insufficient, even if established, to justify the 
factual determination urged (40 CFR 178.32(b)(3)). Nothing in Exhibits 
12-13 provides any information that substantively differs from the 
information summarized in the comments. Second, even assuming that the 
analysis in Exhibit 14 is valid, on its face the submission states that 
the analysis only addresses 95% of the samples chosen by the study; no 
information was provided to explain how the samples relate to the state 
or other geographic area in which carbofuran would be used. This is 
important because NAWQA samples were not evenly distributed across most 
states, but tended to be concentrated in particular regions; in 
statistical parlance, the samples were not collected randomly. The maps 
in Exhibit 14 clearly demonstrate that the study samples were not 
randomly distributed across the state but were primarily in the 
southern and eastern portions of each state, even though carbofuran use 
is not restricted to those portions of the states. In other words, no 
evidence was provided that would allow the Agency to determine the 
percentage of the carbofuran use area represented by the 95% of the 
samples the Petitioners' analysis addressed. Nor was any information 
provided to document the significance of the remaining 5% of the 
samples that were not captured by their analysis; for example, although 
this may have only represented 5% of the samples, it is not clear 
whether this 5% relates to only 5% of the areas where carbofuran may be 
used, or whether it actually represent a far greater percentage of the 
use area.
    iii. Denial of objection. EPA denies this objection on several 
bases.
    The contention that the NAWQA monitoring data--or indeed any 
available carbofuran monitoring data--provide an adequate basis for 
concluding that concentrations will remain low in the areas where use 
is now permitted is incorrect. The NAWQA program focuses on ambient 
water rather than on drinking water sources, is not specifically 
targeted to the high use area of any specific pesticide, and is sampled 
at a frequency (generally weekly or bi-weekly during the use season) 
insufficient to provide reliable estimates of peak pesticide 
concentrations in surface water. For example, significant fractions of 
the data may not be relevant to assessing exposure from carbofuran use, 
as there may be no use in the basin above the monitoring site. Unless 
ancillary usage data are available to determine the amount and timing 
of the pesticide applied, it is difficult to determine whether non-
detections of carbofuran were due to a low tendency to move to water or 
from a lack of use in the basin. As a consequence, the data do not 
support relying on the non-detections as a lower bound, or relying on 
the detections as an upper bound. The program, rather, provides a good 
understanding on a national level of the occurrence of pesticides in 
flowing water bodies that can be useful for screening assessments of 
potential drinking water sources, especially for those assessments 
concerned with chronic, rather than acute toxicants.
    While there have been additional groundwater monitoring studies 
that included carbofuran as an analyte, there has been no additional 
monitoring targeted to carbofuran use in areas where aquifers are 
vulnerable, and the locations of sampling and the sampling frequencies 
generally are not sufficient to capture peak concentrations of the 
pesticide in a watershed or aquifer where carbofuran is used. Capturing 
these peak concentrations is particularly important for assessing risks 
from carbofuran because the toxicity end-point of concern results from 
single-day exposure (acute effects). Pesticide concentrations in ground 
water are generally the result of longer-term processes and less 
frequent sampling can often adequately characterize peak ground water 
concentrations. However, such data must be targeted at vulnerable 
aquifers in locations where carbofuran applications are documented in 
order to capture peak concentrations. As a consequence, monitoring data 
tends to underestimate exposure for acute endpoints.
    EPA also disagrees that the Petitioners' criteria of soils composed 
of 90% sand and less than 1% organic matter, and wells of less than 30 
feet define all of the conditions under which ground water sources are 
vulnerable to carbofuran leaching. No comprehensive analysis was 
provided evaluating how they reached this conclusion. Although the 
Petitioners proposed these criteria as restrictions on the carbofuran 
label, the spatial extent of the label restrictions was not provided. 
Moreover, as discussed in greater detail in EPA's Response to Comments, 
the information provided as part of the Petitioners' comments 
(primarily maps depicting areas identified as vulnerable) was not 
sufficient to allow the Agency to evaluate their claim (Ref. 84). For 
example, the percent sand, one of the criteria used in this analysis, 
varies significantly across a field and the whole range of soil 
textures may occur at a county-level. The national map provided 
purports to represent this parameter and several others aggregated 
together to identify vulnerable locations. This national-scale map does 
not provide the level of detail needed to verify the combination of 
paramters at locations identified as vulnerable.
    While the assertion that soils with 90 percent sand are the most 
vulnerable to leaching is in part true, it is misleading. While many 
states have only small areas of sandy soils, several of the states in 
which carbofuran would continue to be used under the Petitioners' 
proposals have quite extensive areas. For example, according to the 
Petitioners' own assessment of states with high amounts of carbofuran 
application (Ref. 6), Texas had 4.2% of soils classified ``as sand'', 
Michigan had 21.3% and Nebraska had

[[Page 59656]]

26.3%. In addition, the Petitioners' statements imply that soils that 
are sandy textured define the universe of soil textures that are 
vulnerable to leaching. It is possible that more fine-textured soils, 
for example sandy loams or silt loams, could also be sufficiently 
permeable to result in carbofuran leaching as it has not been 
established how much of a reduction in leaching might occur as texture 
becomes finer. Furthermore, finer textured soils tend to have more 
cracks and root channels and thus are more prone to preferential flow.
    Petitioners' claims regarding pH concentrations are also incorrect. 
As an initial matter, their analysis fails to prove that pH values in 
all use areas will ensure that concentrations are below the level of 
concern because the analysis in Exhibit 14 is based on a flawed 
statistical analysis. The methodology on which the Petitioners relied--
the use of the mean minus two standard deviations--to estimate the 5th 
percentile (i.e., 95% of the samples above the value) of the 
distribution of ground water pHs in a state depends strongly on the 
shape of the distribution. This method relies on three assumptions: 1) 
That the data is randomly sampled, 2) that the samples are normally 
distributed (i.e., a bell-shaped distribution), and 3) that the samples 
are independent (i.e., the sampling locations do not share common 
characteristics and are not clustered). The maps in Exhibit 14 clearly 
demonstrate that the study samples were not randomly collected across 
each state but were primarily in the southern and eastern portions of 
the states, even though carbofuran use is not restricted to those 
portions of the states. For example, Figure 1 in Exhibit 14 clearly 
shows that the vast majority of the wells sampled in North Dakota and 
South Dakota are in the eastern half of the state, and in Nebraska in 
the southern and eastern parts. Therefore the wells sampled will not be 
representative of the full distribution of wells in the state. On the 
second assumption, the analysis provided by the Petitioners did not 
determine whether the distribution was normal; the accuracy of 
percentiles at the tails of the distribution, such as the 95th 
percentile, are very sensitive to the accuracy of this assumption. 
Environmental data are usually not normally distributed; log-normal 
distribution is more typical (Ref. 60). If the shape of the 
distribution is not known, a non-parametric or `empirical' estimation 
of the percentiles is better because it does not depend on the same 
assumption of normal distribution. Finally, the pH in various wells may 
or may not be statistically independent. Samples taken across the 
landscape are usually spatially correlated up to a certain distance. 
Beyond that distance, they are statistically independent. 
Unfortunately, this was not determined as part of this analysis. While 
pH is clustered across the state, there is considerable spatial 
variability in pH conditions for both the subsurface and surface 
environments. This is especially true for shallow ground water systems, 
where local conditions can greatly affect the quality and 
characteristics of the water. This can be seen by comparing differences 
in pH values between counties within a state, and noting that even 
within a county individual wells will consistently yield ground water 
with either above- or below-average pH values for that county. 
Furthermore, even if the statistical calculations was correct, by 
definition this evidence would not support a determination that 
groundwater concentrations would never exceed 1.1 ppb, as 5 percent of 
the samples would result in concentrations that are higher.
    In conducting its modeling for the final rule, EPA examined readily 
available data with respect to ground water and soil pH to evaluate the 
spatial variability of pH in Wisconsin. As part of the final rule, EPA 
explained that ground water pH values can span a wide range; this is 
especially true for shallow ground water systems, where local 
conditions can greatly affect the quality and characteristics of the 
water (higher or lower pHs compared to average values). As noted even 
within counties in the same state, wells will consistently yield ground 
water with either above- or below-average pH values for that county. 
Thus, EPA concluded that average ground water pH values for a given 
area do not truly characterize the (temporal and especially spatial) 
heterogeneity common in most areas. The actual significance of using a 
single pH even if it is a 95th percentile value, which as described 
above was not demonstrated to be accurately calculated, is not clear. 
For this reason, EPA bracketed potential exposure using a range of pH 
values.
    As further explained in the final rule, the considerable spatial 
variability in pH conditions for both the subsurface and surface 
environments is significant because the pH has a large effect on the 
persistence of carbofuran. This is demonstrated by the results of the 
ground water modeling simulations from the South-Central Wisconsin 
scenario, which show that what might appear as relatively small 
variations in soil pH can have a significant impact on estimates of 
carbofuran in ground water. Under more acidic conditions, the 
hydrolysis half-life increases from 28 days at pH 7 to years or more at 
pHs less than 6. Further, the results of EPA's corn ground water 
simulations (bounded by the high and low pH values of the aquifer 
system underlying the scenario location) showed that a relatively small 
(0.5) decrease in pH from 7 to 6.5 resulted in an increase by 4 orders 
of magnitude in the 1-in-10-year peak concentration of carbofuran.
    The ground water simulations reflect variability in pH by modeling 
carbofuran leaching in four different pH conditions (pH 5.25, 6.5, 7.0, 
and 8.7), representing the range in the Wisconsin aquifer system. The 
upper and lower bound of pH values that EPA chose for this assessment 
were measured values from the aquifer, and the remaining two values 
were chosen to reflect common pH values between the measured values. 
Estimated 1-in-10-year peak ground water concentrations at pH 7 are 
1.6x10-3 ppb; however, the estimated 1-in-10-year peak 
ground water concentration at pH 6.5 is 16 ppb, nearly 4 orders of 
magnitude greater. EPA explained that, because of carbofuran's 
sensitivity to pH, the Agency had concerns that any given set of 
mitigation measures would not successfully protect groundwater source 
drinking. Data indicate that pH varies across an agricultural field, 
and also with depth (Ref. 49). In particular, the pH can be different 
in groundwater than in the overlying soil. The upper bound of the 
carbofuran concentrations estimated by EPA at pH 6.5 is much greater 
than the concentrations the Petitioners reported in their objections. 
EPA's complete assessment of the 2008 revised label can be found in its 
Response to Comments document and these issues were addressed in more 
detail there (Ref. 84).
    For all of these reasons, the objection is therefore denied.
    c. Objection/hearing request subissue: Consistency with groundwater 
concentration in NMC-CRA. Petitioners object that EPA's estimates in 
the final rule are inconsistent with the groundwater concentration 
estimates EPA developed for the NMC (CRA). However, they do not 
identify any specific inconsistency, they simply make the general 
allegation. They allege that, by contrast, their assessment, which 
estimated maximum concentrations of 1.1 ppb, is consistent with the NMC 
CRA.
    i. Background. The NMC CRA examined carbofuran at two sites, 
northeastern Florida and the Delmarva Peninsula. In Florida, 
concentrations

[[Page 59657]]

were found to be below levels of concern because of high pH, but in 
Delmarva, both in corn and in melon scenarios EPA estimated that 90% of 
daily concentrations could be as high as 20.5 and 25.6 ppb, 
respectively. In the proposed and final rules, EPA cited the modeling 
conducted for the NMC to support its estimates. In addition, EPA used 
the same methodology used to develop the estimates for the NMC CRA, to 
conduct the modeling for the additional crops and locations on which 
carbofuran use occurs.
    Although the Petitioners alleged that their estimates were 
consistent with the NMC CRA in their comments on the proposed rule, 
they did not identify any specific inconsistency between EPA's 
groundwater estimates for the proposed rule and its estimates for the 
NMC CRA.
    ii. Denial of hearing request. EPA denies the request for a hearing 
on this subissue because there is no disputed factual matter for 
resolution. There is no dispute as to the methodology EPA used to 
conduct its modeling in either assessment. Petitioners have not 
identified any specific inconsistency between EPA's groundwater 
exposure assessment conducted for this rule and the assessment 
conducted for the NMC CRA. Instead, they rely on mere allegations and 
denials. As EPA's regulations make clear, a mere ``denial'' of an EPA 
position is not sufficient to satisfy the standard for granting a 
hearing (40 CFR 178.32(b)(2)). Moreover the question of whether EPA's 
assessments are consistent requires the application of a legal standard 
to undisputed facts, and is thus a legal or policy question. Hearings 
are not appropriate on questions of law or policy (40 CFR 
178.32(b)(1)). (73 FR 42696-42697) (denying a hearing on EPA's decision 
to reduce the children's safety factor, in the absence of data from the 
endocrine screening program, on the ground that the objection 
constituted a legal issue). FDA has repeatedly confirmed that the 
application of a legal standard to undisputed facts is a question of 
law for which a hearing is not required. (See, e.g., 68 FR 46403, 46406 
n.18, 46408, 46409 (August 5, 2003) (whether facts in the record show 
there is a reasonable certainty of no harm is a question of law; 
whether a particular effect is a ``harm'' is a question of law)).
    Neither does the claim that their modeling is consistent with the 
NMC CRA justify a hearing on this question. As EPA explained in the 
final rule, the values estimated in the modeling conducted for the NMC 
CRA are greater than the 1 ppb that FMC claims is the maximum expected 
1-in-10-year peak concentration. A hearing is not warranted where the 
claim is clearly contradicted by the record (40 CFR 178.32(b)(2)). See, 
e.g., 57 FR 6667 (February 27,1992) (``A hearing must be based on 
reliable evidence, not on mere allegations or on information that is 
inaccurate and contradicted by the record.''); 49 FR 6672 (February 22, 
1984) (hearing denied where claim was based on demonstrably false 
premise).
    iii. Denial of objection. As discussed in the final rule and 
response to comments document, the Petitioners' results are not 
consistent with the estimates developed for the NMC CRA. The NMC CRA 
examined carbofuran at two sites, northeast Florida and the Delmarva 
Peninsula. In Florida, concentrations were found to be below levels of 
concern because of high pH, but in Delmarva, both in corn and in melon 
scenarios EPA estimated that 90% of daily concentrations could be as 
high as 20.5 and 25.6 ppb, respectively. These values are greater than 
the 1 ppb that Petitioners claim is the maximum expected 1-in-10-year 
peak concentration.
    2. Objections relating to surface water exposure estimates--a. 
Objection/hearing request subissue: Use of percent of the crop treated 
(PCT) in surface water modeling. The Petitioners object to the 
assumption in the surface water assessments in the final rule that 100% 
of the crops in a watershed will be treated with carbofuran. The 
Petitioners argue that actual carbofuran sales data on a county basis 
from 2002-present demonstrate that the current carbofuran PCT is less 
than 4.25%. Using this PCT, and taking into account the recently 
submitted ``no application buffers,'' the Petitioners allege that the 
modeling in Exhibit 15 demonstrates that carbofuran concentrations in 
surface water will not exceed 1.1 ppb, ``which is below the level of 
concern.''
    In support of this objection, the Petitioners reference county 
level sales data that were submitted to the Agency on November 7, 2008, 
after the close of the comment period. They also reference the use 
tracking system proposed in their recent registration amendments 
(Exhibit 2) and the modeling contained in Exhibit 15.
    i. Background. To conduct an assessment of a pesticide's potential 
to contaminate surface water, EPA estimates the percentage of farmland 
in a watershed on which a particular crop is grown (e.g, corn); this is 
referred to as the percent cropped area (PCA). EPA then assumes that 
100% of the cropped area is treated with the pesticide that is the 
subject of the assessment. In the proposed rule, EPA explained that the 
reason for its assumption that 100% of PCA in a watershed is treated is 
due to the large uncertainties in the actual PCT on a watershed-by-
watershed basis. EPA developed an extensive discussion of the 
uncertainties in PCT and how they impact drinking water exposure 
assessment in its proposed rule (73 FR 44885 (July 31, 2008)), and in a 
background document previously provided to the SAP considering the 
draft carbofuran NOIC (Ref. 45). The data are generally not available 
on the scale necessary to allow for reliable estimates of pesticide use 
in a watershed. Such data are generally available only on a statewide 
basis, and if such estimates are used to account for PCT, it will 
underestimate the risks for some drinking water facilities in the 
state, as these estimates represent only a state-wide average. In some 
cases this underestimate can be substantial, because usage may not be 
evenly distributed across the landscape; due to differences in factors 
like pest pressure, local consultant recommendations, and weather, it 
may be much higher in some areas. Further, temporal uncertainties can 
result in changes in use that might be driven by weather, changes in 
insect resistance over time, and changes in agronomic practices. To 
date, methods that account for this uncertainty, given the nature of 
the available data, have not been developed. EPA explained that as a 
consequence, the Agency could not accurately estimate a drinking-water 
watershed scale PCT that, when used in a quantitative risk assessment 
on a national or regional basis, standing alone, provides the necessary 
level of certainty to allow the Agency to confidently conclude that 
exposures will meet the FFDCA section 408 safety standard. EPA also 
described the results of a sensitivity analysis conducted using a low 
PCT estimate.
    In their comments on the proposed rule, the Petitioners criticized 
the Agency for this assumption, arguing that because carbofuran is used 
on such a low percentage of crops nationally that it is unrealistic to 
assume that such a large percentage of any individual watershed would 
be treated. To support their claims that the PCT would generally be 
below 4%, they referenced county-level ``use'' data, but failed to 
provide either the data or methodology on which they relied until after 
the close of the comment period.
    In the final rule, EPA explained at length the reasons that the 
information provided during the comment was insufficient to allow the 
Agency to reliably estimate a lower PCT for carbofuran. EPA did not 
review the information submitted after the close of

[[Page 59658]]

the comment period. However, based on the information that could be 
gleaned from the description in the comments, EPA explained that the 
data on which they relied did not appear to be ``use'' data, but sales 
data, and that both the data and methodology failed to support the 
claims made in the Petitioners' comments. The Agency also described the 
results of a sensitivity analysis conducted to determine the impact 
that PCT could have on the risk assessment, which demonstrated that 
even assuming that a low percentage of a watershed is treated with 
carbofuran, exposures will still be unsafe for infants.
    ii. Denial of Hearing Request. To the extent Petitioners' objection 
is limited to EPA's refusal to use a 4% PCT in estimating drinking 
water concentrations, EPA has concluded that the objection does not 
warrant a hearing because the Petitioners' objection on this subissue 
is irrelevant, and therefore immaterial, with regard to EPA's final 
tolerance revocation. The Petitioners have not responded to EPA's 
explanation in the final rule of the reasons that the information and 
methodology on which they relied to estimate a 4% PCT was flawed. As 
discussed in the final rule, EPA had assumed that the data on which 
they were relying was sales data, and so the resubmission of the 
information sent in after the close of the comment period only confirms 
that the Agency's analysis was correct; it does not rebut EPA's 
substantive concern that such information is insufficient to support 
the conclusions the Petitioners assert. In essence, the Petitioners 
ignored EPA's extensive analysis of this issue in the final rule and 
simply refiled their comments on the proposal as if EPA's determination 
in the final rule did not exist. The statute, however, requires that 
objections be filed on the final rule not the proposal. By ignoring 
EPA's final rule on this issue, Petitioners have failed to lodge a 
relevant objection. When an objector does not challenge EPA's 
conclusions in the final rule, but merely reiterates comments made on 
the proposed rule, without submitting some evidence that calls EPA 
final rule conclusions into question, the objector has not raised a 
live controversy as to an issue material to the final rule (See 73 FR 
42698-42699 (July 23, 2008) (denying several NRDC hearing requests 
because the objections were based on EPA's preliminary DDVP risk 
assessment, rather than the revised risk assessment published with the 
final order); 53 FR 53176, 53191 (December 30, 1988) (where FDA 
responds to a comment in the final rule, repetition of the comment in 
objections does not present a live controversy unless the objector 
proffers some evidence calling FDA's conclusion into question)).
    An additional flaw in this objection is that the proffered evidence 
is untimely and insufficient. Neither the proposed registration 
amendments nor the evidence submitted as part of this objection, 
including the modeling in Exhibit 15, was provided to the Agency during 
the comment period. The modeling in Exhibit 15 was available, because 
it was summarized in Petitioners' comments; however the underlying 
modeling was withheld. Equally, there is no evident reason that the 
sales data could not have been submitted as part of the Petitioners' 
comments. Petitioners relied on this data to perform analyses completed 
in 2006-2007, for purposes of the January 2008 SAP review of the draft 
carbofuran NOIC, so the information was available long before their 
comments needed to be filed. Accordingly, as discussed in Unit VI.D, 
this information is not appropriately considered as a basis for 
justifying a hearing on its final rule. Moreover, as explained below, 
because no evidence was submitted in support of the newly proposed use 
tracking system, reliance on that proposal to support a low PCT 
constitutes nothing more than an allegation. This is not an adequate 
basis on which to grant a hearing (40 CFR 178.32(b)(2)). Finally, to 
the extent this objection relies on Petitioners' recently proposed risk 
mitigation measures, as discussed in Units VI.C and D, objections and 
hearing requests based on these new risk mitigation measures are not 
appropriately considered at this stage of the administrative process, 
and are denied as immaterial (40 CFR 178.32(b)(3)).
    iii. Denial of objection. While the Agency typically uses PCT in 
developing estimates of pesticide residues in food, this is entirely 
different than developing estimates of the percent of a watershed that 
is treated for purposes of estimating drinking water exposures. Food is 
generally randomly distributed for sale across the nation without 
regard to where it is grown. This tends to even out any PCT variations 
that may arise on local levels. By contrast, the source of water 
consumption (and consequently exposure) is localized, either in a 
private well or a community water system. The PCT in any watershed will 
therefore directly impact the residues to which people living in that 
watershed will be exposed.
    For this reason, among others, for drinking water exposure 
estimation, the Agency assumes that 100% of the cropped area (or 100% 
PCT) is treated with the pesticide. EPA also makes this assumption due 
to the large uncertainties in the actual PCT on a watershed-by-
watershed basis. EPA included an extensive discussion of the 
uncertainties in PCT and how they impact drinking water exposure 
assessment in its proposed rule (73 FR 44834) and in a background 
document provided to the SAP considering the draft carbofuran NOIC 
(Ref. 45). Because usage is often not evenly distributed across the 
landscape, due to differences in factors like pest pressure, local 
consultant recommendations and weather, it may be much higher in some 
areas. Further, temporal uncertainties can result in changes in use 
that might be driven by weather, changes in insect resistance over 
time, and changes in agronomic practices. To date, methods that account 
for this uncertainty, given the nature of the available data, have not 
been developed. Consequently, EPA cannot accurately estimate a 
drinking-water watershed scale PCT that, when used in a quantitative 
risk assessment on a national or regional basis, standing alone, 
provides the necessary level of certainty to allow the Agency to 
confidently conclude that exposures will meet the FFDCA section 408 
safety standard.
    In most cases, EPA agrees that it is unlikely that 100% of the crop 
will be treated with a single pesticide in most watersheds, 
particularly in larger watersheds. However, for small watersheds, it is 
reasonable to assume that an extremely high percentage of the crops in 
the watershed may be treated.
    Moreover, EPA has an obligation to evaluate all legally permitted 
use practices under the label, and to ensure that all such use meets 
the requisite statutory standards, not simply to base its decisions on 
the practices the majority might typically use. The September 2008 
proposed label, submitted during the comment period, imposes no 
restriction on the application of carbofuran related to whether a 
particular percent of the watershed has been treated. Thus, even with 
the restrictions on FMC's September 2008 labels, it remains legally 
permissible for 100% of the watershed to be treated with carbofuran.
    Nor is EPA aware of an enforceable mechanism to ensure that farmers 
applying pesticide to their individual fields will have the ability to 
indendently determine whether a particular percentage of the watershed 
has been treated. There are significant practical difficulties inherent 
in implementing such label directions, as

[[Page 59659]]

they force individual growers to have continual knowledge of the 
variances of the behavior of other farmers across the entire watershed. 
While for small watersheds that involve only one or two farms it might 
be feasible for neighbors to independently coordinate applications with 
respect to adjacent fields, for larger watersheds or for smaller 
watersheds with multiple farms, the practical difficulties increase 
significantly. And as explained below in Unit VI.F.2.D, significant 
questions remain regarding the efficacy of Petitioners' proposed use 
tracking system.
    However, in the final rule, EPA conducted a sensitivity analysis to 
explore the impact of the PCT assumption on dietary risk using an 
assumed 10% PCT, a figure proposed previously by FMC (74 FR 23065-
23066). The results of that analysis demonstrated that even at these 
low percentages, which may significantly underestimate exposures, 
particularly in small watersheds, carbofuran exposures from drinking 
water contribute significantly to children's dietary risks. EPA 
conducted a similar sensitivity analysis for the final rule, discussed 
below in Unit VI.F.3, which demonstrates that even assuming that a low 
percentage of a watershed is treated, exposures will still be unsafe 
for infants.
    Since EPA's 2006 determination that carbofuran does not meet the 
safety standard, FMC has submitted three assessments that relied in 
part on what they refer to as ``county-level usage data'' (Refs. 29, 
74, and 89). Based on the information provided with the objections, the 
original source of the ``county-level usage data'' is sales data, 
apparently collected at the distributor level. The Petitioners claim to 
have augmented these sales data in an unspecified manner, by 
incorporating information from the distributors, which was used to 
allocate carbofuran usage at the county level. In their comments on the 
proposed rule, the Petitioners provided maps representing county level 
and watershed-scale use estimates, but did not provide the actual usage 
estimates in any clearly understandable format.
    The Petitioners did submit these sales data as part of their 
objections, but have provided only a limited description of how these 
data were collected and no description of how they were actually 
analyzed or validated; what was characterized as ``careful and proven 
techniques to capture this data'' were not described. The method used 
to attribute carbofuran sales to counties was not described. Nor have 
they explained what is meant by negative usage estimates.
    The Agency agrees that county-level use data would be useful in 
generating reasonable estimates of PCT that might be appropriately used 
in drinking water assessments. However, no usage data have been 
provided. Rather, the Petitioners only provided county-level use 
estimates for Illinois, although they have not submitted the analyses 
that presumably are the basis for the estimates. County-level estimates 
to support other risk assessments have not been submitted by the 
Petitioners. Further, the Petitioners have provided limited 
characterization of the source data, noting that these data were 
derived from FMC billings and ``EDI data'', but they did not provide 
either the billings or the EDI data, nor explain how they were 
collected.
    There are two major problems in equating sales information with use 
information: (1) Mapping the point and time of sale to the point and 
time of use and (2) allocating the amount sold across the crops on 
which it can be used. The submission did not explain how either of 
these two problems was resolved.
    The first problem is highlighted by the fact that for some county/
crop/year combinations in the submitted tables, estimated usage is 
negative. Use of a pesticide clearly cannot be negative, but sales at a 
particular point and time can be negative because buyers can return 
unused product. The fact that some usage estimates are negative 
suggests that buyers are returning carbofuran product purchased in an 
earlier time period or from another location. But if farmers are 
returning carbofuran purchased in a previous time period, any 
assessment must also account for the possibility that they also could 
use stocks purchased previously. Thus, use in a given year may be 
greater than sales in that year. Similarly, if farmers are returning 
carbofuran purchased in another location, it must be recognized that 
they could be using carbofuran purchased in another location. Thus, use 
in any given county or watershed could be greater than sales in that 
locality. That is, regardless of whether the issue is use over space, 
time, or both, the results are that usage will be underestimated in 
some localities. Further, zeroing out the negative values will not 
result in appropriate estimates; the negative usage estimates merely 
make the problem manifest. Even total sales at a point in time may 
underestimate actual use.
    The second problem arises with the allocation of product sales 
across the crops on which it can be used. The data provided as part of 
the objections were aggregated for all crops, including crops on which 
use is no longer allowed, such as cotton or alfala; the data were not 
collected based on the individual crops. No explanation is provided to 
indicate how the Petitioners divided the quantity sold between the 
amount used on cotton, on alfalfa, and on all other crops. Since part 
of the purpose of the Petitioners' assessment is presumably to show 
that eliminating the use on the cancelled crops, such as alfalfa, will 
sufficiently reduce any risks, it is critical to know how they 
determined the amount used on alfalfa as opposed to other crops, and it 
is difficult to imagine how this could be done with any accuracy. For 
example, one could assume that the chemical is used on equal proportion 
of all crops, but there is no basis for such an assumption. It might 
not matter if all EPA were interested in was the total amount used in 
an area, but this is not useful for purposes of assessing the risk on a 
smaller scale, such as in the present case.
    The method the Petitioners used to generate use estimates from the 
sales data does not account for the uncertainties described above nor 
for the potential for use to be locally concentrated due to pest 
pressures. The method that is summarily described as having been used 
to allocate county-level usage estimates to watersheds appears to be 
similar to a method that has been used by others to calculate ``best-
estimate'' county-level PCT (Ref. 73) to map nationwide pesticide 
usage. However, these methods are not appropriate for calculating PCTs 
for surface drinking water sources or watersheds that drain to 
community water systems, because they do not adequately account for the 
uncertainty in the data at the appropriate spatial scale. This 
methodology produces an estimate that is a measure of central tendency 
and, as such, roughly half the estimated values will underestimate the 
PCT. Furthermore, because pesticide use varies from year to year, and 
can in some cases be patchy, with high levels of use in small areas and 
little use in most areas, the underestimates of PCT can be substantial 
in small watersheds. As previously noted, methods for calculating PCT 
that account for these uncertainties have not been developed. 
Accordingly, EPA denies this objection.
    b. Objection/hearing request subissue: Results of FMC modeling. The 
Petitioners claim that the prior surface water assessments submitted to 
the Agency demonstrated that carbofuran concentrations in surface water 
were not expected to exceed 1.1 ppb. They claim

[[Page 59660]]

that these studies provide further confirmation of the results of the 
new modeling conducted to support their objections, which also 
concluded that concentrations would be less than 1.1 ppb. In support of 
this objection, the Petitioners reference the previously submitted 
studies, along with the modeling provided in Exhibit 15. The modeling 
in Exhibit 15 appears to be the modeling that was originally summarized 
in their comments, but that the Petitioners withheld. The modeling was 
also supplemented to account for the newly proposed registration 
amendments submitted as part of the objections.
    i. Background. In their comments, the Petitioners alleged that the 
results of their modeling showed that concentrations of carbofuran in 
surface water would not exceed 1.1 ppb. The comments referenced two 
surface water assessments that they had submitted to the Agency prior 
to the proposed tolerance revocation: a surface water assessment based 
on an Indiana Community Water System (CWS) (Refs. 89 and 90) and an 
assessment based on the Watershed Regressions for Pesticides (WARP) 
model. They also summarized additional surface water modeling that had 
been conducted to support their comments on the proposed rule, a 
Nationwide Community Water System Assessment (Ref. 57), but did not 
submit the actual modeling, or identify or describe in detail the model 
on which they relied.
    In the final rule, EPA explained the flaws in all of the 
Petitioners' assessments that caused the Agency to reject the studies' 
conclusions. For the two assessments that had actually been submitted 
to the Agency, EPA was able to definitively explain the flaws. With 
respect to the Nationwide CWS modeling that was summarized in their 
comments, EPA evaluated the modeling based on the information it was 
able to glean from the description provided in the comment discussion.
    ii. Denial of hearing request. A hearing is denied on this subissue 
because EPA has concluded that Petitioners' objection on this issue is 
irrelevant, and therefore immaterial, with regard to EPA's final 
tolerance revocation regulation (40 CFR 178.32(b)(3)). In the final 
rule, and in other rulemaking documents, EPA provided a detailed 
explanation of the bases for its conclusions that the previously 
submitted assessments were invalid (74 FR 23062-23064 (May 15, 2009)). 
Petitioners have not challenged EPA's explanation, nor explained how 
the resubmission of the same studies addressed the substantive issues 
EPA raised. Because Petitioners ignored EPA's extensive analysis of 
this issue in the final rule, they have essentially refiled their 
comments on the proposal as if EPA's determination in the final rule 
did not exist. The statute, however, requires that objections be filed 
on the final rule, not on the proposal (21 U.S.C. 346a(g)(2)). By 
ignoring the EPA's final rule on this subissue, Petitioners have failed 
to lodge a relevant objection. Petitioners' resubmission of the exact 
same information does nothing to call EPA's conclusion into question, 
which is what is required to maintain their claim at this stage of the 
proceeding. When an objector does not challenge EPA conclusions in the 
final rule, but merely reiterates comments made on the proposed rule 
without submitting some evidence that calls EPA final rule conclusions 
into question, the objector has not raised a live controversy as to an 
issue material to the final rule. (See 73 FR 42700-42701 (July 23, 
2008) (hearing request denied where NRDC failed to challenge EPA's 
conclusion that challenged study is consistent with several other 
studies, but merely reiterated assertions from its original petition 
that the study is not representative); 53 FR 53176, 53191 (December 30, 
1988) (where FDA responds to a comment in the final rule, repetition of 
the comment in objections does not present a live controversy unless 
the objector proffers some evidence calling FDA's conclusion into 
question)).
    With respect to the modeling submitted in Exhibit 15, this evidence 
is untimely. The modeling submitted in Exhibit 15 appears to be a 
fuller description of Petitioners' National CWS Assessment, which was 
described but not provided as part of their comments on the proposed 
rule. The modeling also has been revised to account for the newly 
proposed risk mitigation measures. However, even with the greater 
detail provided, the information contained in Exhibit 15 still fails to 
address many of the deficiencies EPA identified in the final rule. For 
example, although some further detail has been provided of how the 
Petitioners modeled the vegetated buffer strip, the complete 
information EPA would need to assess the modeling was not provided; the 
material provided is insufficient to understand how the simulations 
were performed or how the simulations were parameterized. Nor have the 
Petitioners submitted the inputs used in modeling estimated 
concentration from spray drift. As discussed in Unit VI.D, because the 
modeling in Exhibit 15 was not provided during the comment period, and 
to the extent that the detailed information EPA identified as lacking 
in the final rule has still not been provided, the evidence submitted 
in Exhibit 15 is not appropriately considered as a basis for justifying 
a hearing on its final rule. And in the absence of this evidence, this 
objection consists of mere allegations and general denials, which are 
inadequate to justify a hearing (40 CFR 178.32(b)(2)).
    Further, to the extent that this objection relies on the ``no 
application buffers,'' or the proposed use tracking system newly 
submitted as part of their objections to support the models' assumption 
of a low PCT, the hearing request is denied as irrelevant, and 
therefore immaterial, to EPA's determination in the May 15, 2009 final 
rule, for the reasons discussed in Unit VI.C. Petitioners are actually 
not objecting to the conclusions in EPA's final rule; rather, they are 
suggesting that EPA might reach a different result in a different 
factual scenario. Objections, however, must be directed ``with 
particularity [at] the provisions of the regulation or order deemed 
objectionable'' (21 U.S.C. 346a(g)(2). And, as explained below, because 
no evidence was submitted in support of the newly proposed use tracking 
system, reliance on that proposal to support a low PCT constitutes 
nothing more than an allegation. This is not an adequate basis on which 
to grant a hearing (40 CFR 178.32(b)(2)).
    iii. Denial of objection. To the extent this objection relies on 
Petitioners' newly submitted registration amendments, the objection is 
denied as immaterial. EPA also denies the remaining objections because, 
based on its review of the submitted modeling, EPA has concluded all of 
the modeling has substantial flaws that render the model results 
invalid. EPA has previously reviewed these assessments, and provided a 
detailed explanation of the reasons for the Agency's conclusions, most 
recently, in the final rule and the associated response to comments (74 
FR 23060-23064, Ref. 84). EPA's reasoning is summarized briefly below.

Indiana CWS Assessment

    EPA has previously reviewed the Indiana surface water assessment, 
and has provided comments on that submission (Ref. 45), many of which 
were reiterated at length in the final rule and response to comments 
documents (74 FR 23062-23064, Ref. 84). The Petitioners originally 
submitted this study to demonstrate that ``EPA's standard index 
reservoir scenario

[[Page 59661]]

overestimates surface water concentrations compared with expected 
concentrations in actual Indiana CWS where carbofuran is used.'' The 
Index Reservoir is designed to be used as a screen, and as such, 
represents watersheds more vulnerable than most of those that support a 
drinking water facility. It is thus protective of most drinking water 
on a national basis. That, however, does not mean that EPA believes 
this scenario overestimates concentrations for all drinking water 
reservoirs. EPA agrees that it is an appropriate refinement to simulate 
local and regional watersheds, and has in fact done so (Refs. 44, 46, 
47, 48, and 84). However, for the reasons discussed below, EPA does not 
believe that the Petitioners' assessment demonstrates that carbofuran 
concentrations will not exceed 1.1 ppb in Indiana surface water sources 
of drinking water. Even accepting the Indiana surface water assessment 
at face value, the estimated 1-in-10-year peak concentrations at some 
facilities were as high as 6.88 [micro]g/L, and these concentrations 
substantially exceed the 1.1 ppb concentration the Petitioners now 
claim represent reasonable estimates.
    The study also fails to support the Petitioners' other conclusions. 
The study was originally intended to demonstrate two points: (1) That 
the vulnerability of the Indiana CWS ``brackets'' the Index Reservoir, 
and (2) that the concentrations they estimated for these locations are 
significantly less than EPA estimates. Regarding the vulnerability of 
the CWS, the assessment describes their approach for modifying the 
parameters of the Index Reservoir scenario to represent 15 reservoir-
based watersheds in Indiana cropped in corn. The study indicates the 
Petitioners have included data that, based on EPA's review of these 
submissions, are not available at the appropriate scale to determine 
all site-specific parameters. The Petitioners modified some of the 
parameters based on available data to represent more localized 
conditions that are more or less vulnerable than for the Index 
Reservoir. From the description, the Petitioners' approach is similar 
to the methods that EPA uses to develop new scenarios, in that soil and 
weather data are varied in order to represent different locations. 
However, for other parameters, EPA believes the modifications are 
inconsistent with fundamental assumptions upon which the modeling is 
based. In previous submissions to the Agency, FMC has described that 
they have made modifications to scenarios to reflect local conditions 
of each CWS in Indiana by modifying the soil and weather data and 
altering the ratio of watershed drainage area to the reservoir capacity 
(Ref. 89). EPA agrees that soil and weather data can be modified to 
reflect conditions at local watersheds. However, EPA disagrees that 
altering the ratio of watershed drainage area to the reservoir capacity 
(i.e., the DA/NC) is a reasonable modification.
    The DA/NC parameter is associated with increased concentrations in 
drinking water reservoirs to a certain point. The Petitioners adjusted 
their EDWCs for each drinking water facility by a factor representing 
the ratio of the DA/NC for each reservoir divided by the DA/NC for the 
Index Reservoir (which is 12). EPA does not believe this is appropriate 
for two reasons. First, the relationship between concentrations and the 
DA/NC is not strictly linear. Small DA/NCs imply a small watershed 
combined with a large reservoir. As the DA/NC increases, the relative 
watershed size increases, and thus the runoff volume going into the 
reservoir also increases. This is also means the reservoir's ability to 
dilute the runoff decreases; the result is that concentrations increase 
with an increase in the DA/NC. However, at some point, the runoff 
volume exceeds the reservoir capacity, and rather than increasing the 
pesticide concentration, the excess runoff flows out of the reservoir, 
carrying the pesticide with it. Thus, because pesticide concentrations 
are not linearly related to the DA/NC, it is not appropriate to 
multiply the model output by a linear DA/NC adjustment factor. 
Secondly, the PRZM model, which is used to simulate the watershed for 
the Index Reservoir, is a field-scale model. As the watershed size (and 
the DA/NC) increases, assumptions upon which PRZM relies (namely: 
uniformity of soils, equal and simultaneous movement of runoff to the 
reservoir, and uniform weather across the watershed) no longer hold and 
the model becomes less valid for simulating the runoff processes. The 
geometry of the Index Reservoir was chosen partly to avoid these two 
limitations (Ref. 43).
    The study authors also calculated their own PCA values \19\ for 
this assessment. EPA uses the maximum PCA calculated for any HUC8 (8-
digit hydrologic unit code) watershed in exposure estimates. HUC8s are 
cataloging units for a watershed developed by the USGS and are used as 
surrogates for drinking water watersheds. The process by which PCAs 
were developed and how they are used by the Agency has been vetted with 
the FIFRA SAP (Refs. 30 and 31). The Agency has developed PCAs for four 
major crops--corn, soybeans, wheat, and cotton--and uses a default PCA 
based on all agricultural land for characterizing other crops. The 
Agency has also calculated regional default PCAs for use in 
characterizing regional differences in drinking water exposure. EPA 
limited further development of PCAs for additional crops in response to 
the FIFRA SAP peer review, which concluded that the data were not 
available at the appropriate scale to do so. The Petitioners' 
assessment estimated PCAs for specific watersheds in Indiana, but did 
not provide sufficient detail in their descriptions of how they 
calculated those PCAs to enable EPA to assess their validity.
---------------------------------------------------------------------------

    \19\ The PCA is the fraction of the drinking water watershed 
that is used to grow a particular crop.
---------------------------------------------------------------------------

    Regarding the statement that the concentrations estimated for the 
study locations in Indiana are significantly less than EPA estimates, 
EPA has determined that the Petitioners included an adjustment factor 
to account for the percent of a crop that is treated with carbofuran. 
As previously discussed, EPA does not believe that it is appropriate to 
base its aggregate risk estimates on PCT within watersheds. This is 
because data and/or methods are not available that would allow EPA to 
develop PCT at the watershed scale with the necessary level of 
confidence to allow EPA to make a safety finding. The PCT factors that 
the Petitioners applied would generate significantly lower 
concentrations than those estimated by EPA.

WARP Assessment

    EPA has reviewed the WARP assessment previously and has provided 
comments on the submission (Refs. 45 and 86). The WARP model has not 
been fully evaluated for quantitative use in exposure estimation by the 
Agency, although it has been preliminarily reviewed by the SAP (Ref. 
32). EPA used WARP to select monitoring sites for the herbicide 
atrazine, based on predicted vulnerability of watersheds to atrazine 
runoff within the corn/sorghum growing regions. EPA presented its 
approach to the FIFRA SAP in December 2007. The SAP report concluded 
that ``WARP appears to be a logical approach to identify the areas of 
high vulnerability to atrazine exposure,'' endorsing EPA's use of this 
tool only for atrazine, and for the limited purpose of designing a 
monitoring program. The SAP noted that the most important explanatory 
variable with WARP was use intensity, which underscores the

[[Page 59662]]

importance of having the most accurate data for this parameter.
    WARP is a regression model developed by the USGS to estimate 
concentrations of the pesticide atrazine in rivers and streams. As a 
regression model, it is based on monitoring data from 112 USGS NAWQA 
monitoring locations. WARP does not directly estimate daily 
concentrations, but predicts the percent of the time in a randomly 
selected year that concentrations of the pesticide are less than a 
specified value, with a specified level of confidence. USGS attempted 
to develop an approach to estimate annual time series for other 
pesticides, and concluded that ``further data collection and model 
development may be necessary to determine whether the model should be 
used for areas for which fewer historical data are available * * * 
Because of the relative simplicity of the time-series model and because 
of the inherent noise and unpredictability of pesticide concentrations, 
many limitations of the model need to be considered before the model 
can be used to assess long-term pesticide exposure risks'' (Ref. 92).
    The Petitioners had previously relied on their WARP assessment to 
support the conclusion that the ``maximum 1-in-10-day estimated 
concentrations of carbofuran at the 90th percentile level in Illinois, 
Indiana, Iowa, and Nebraska * * * will be less than or equal to 0.3687 
ppb.'' This is erroneous. WARP does not provide direct estimates of 
return frequency, i.e., 1-in-10 days, but rather percentiles of the 
expected distribution of measurements. This may be similar but not 
identical to the return frequency expressed as a percentile, depending 
on the number of measurements used to support the regression. EPA 
lacked the information necessary to determine whether the contractor 
calibrated the model correctly. However, taking the conclusion at face 
value, the value the Petitioners predicted using WARP, 0.3687 ppb, 
appears to represent the maximum of the estimated values of the annual 
90th percentile among all the sites evaluated. Such a site would be 
expected to have higher concentrations than 0.3687 ppb about 37 days a 
year (10% of the year). Generally, the 90% prediction intervals tend to 
be about plus or minus an order of magnitude. Thus, roughly 5% of such 
sites could have about 37 days a year greater than about 3.7 ppb, or 
over 3-fold higher than the 1.1.ppb concentrations the Petitioners now 
claim will be the maximum concentrations in surface water.
    The Agency also disagrees that the differences between the 
Petitioners' and EPA estimates are only due to Petitioners' use of 
county-level use estimates. Most importantly, the Petitioners relied on 
estimates of 1-in-10-day concentrations, rather than the 1-in-10-year 
peak concentrations estimates used routinely by EPA. 1-in-10-day 
concentrations are not the measurement endpoint EPA uses for human 
health risk assessment and are not appropriate for estimating drinking 
water exposure. The Agency uses 1-in-10-year peak concentrations for 
screening level assessments, and the full time series (typically 30 
years) of daily concentration values for refined assessments. EPA's 
reliance on the 1-in-10-year peak concentration has been reviewed and 
approved by the FIFRA SAP (Ref. 30).
    A concentration that occurs 1-in-10 days occurs 350 times as often 
as a 1-in-10-year event. Using this value instead of the one EPA used 
would result in significantly lower estimates of pesticide water 
concentration and human exposure. For example, EPA's estimate of the 1-
in-10-year peak concentration from the simulation of corn in Kansas 
with a 300 ft buffer was 31.8 ppb. By contrast, EPA's estimate of the 
1-in-10-day concentration from the same simulation was 4.5. Use of the 
1-in-10 day concentration to assess dietary risk would be inconsistent 
with the SAP's advice and EPA's typical practice, as well as with EPA's 
statutory requirement to protect human health.
    EPA disagrees with the Petitioners' claim that ``the extreme nature 
of a 1-in-10-year event would result in dilution effects that cancel 
out any increased loading.'' The Index Reservoir scenario has been 
validated against monitoring collected at the site it was designed to 
represent, Shipman City Lake in Illinois (Ref. 43). This assessment 
showed that the 1-in-10-year event EPA modeled was similar in magnitude 
to the peak value of the pesticide concentrations shown in 5 years of 
monitoring data collected at that site. The 1-in-10-year peak 
concentration calculated for that pesticide (not carbofuran), using the 
Index Reservoir was 33 ppb, while the peak value from 5 years of 
monitoring was 34 ppb.
    EPA cannot determine the validity of the use intensities assumed 
for the Petitioners' assessment. The source of county level use data 
appears to have been sales data at the distributor level, similar to 
the data provided in the Petitioners' November 7, 2008 submission. 
However, as previously explained, the method chosen to estimate county 
level use estimates from the sales data was not provided. The county 
level estimates used in the assessment for 2002 to 2004 for Illinois 
were provided in a table. These estimates for each county were averaged 
over the 3 years for input to the model. A summary description of how 
watershed-scale use estimated from county level use data was provided, 
but because the sales data for the individual crops and the method that 
was used to generate county level estimates were not available, the 
validity of this assessment cannot be evaluated.

Nationwide CWS Assessment

    EPA has previously reviewed the Petitioners' ``Nationwide CWS 
Assessment'' and provided a response to the submission as part of the 
final rule and Response to comments (Ref. 45). As a preliminary matter, 
this assessment only included use intensity for reservoir-based 
systems, and excluded use intensity for all stream- or river-based 
systems from their assessment. Therefore, this assessment provides no 
evidence to demonstrate that carbofuran can be safely used in stream or 
river-based community water systems.
    Similar to the Indiana CWS study discussed above, this study relied 
on county-level usage estimates to estimate use intensity. The National 
CWS Assessment concluded that a use intensity below 2.1 lbs a.i/mi\2\ 
would assure that surface water concentrations will be below the level 
of concern.
    To evaluate the study, it is therefore important to understand how 
the use intensities were derived. The Petitioners' methods have been 
poorly described, but EPA has been able to piece together a general 
sense of the methods from the various reports provided to EPA. To 
summarize, the Petitioners relied on sales data to generate the use 
intensity estimates, but the method used to generate the county-level 
use estimates from the sales data is not described. The actual county 
level use estimates used in the use intensity calculations were not 
provided. There is a limited description indicating only that the 
county level use estimates were apportioned to different crops, but the 
method used to do this was not provided. The Petitioners appear to have 
used an objective method to group the county-level use estimates into 5 
classes, but the method is only briefly described. Thus, because EPA 
cannot determine how use intensity was estimated, the Agency cannot 
determine if the conclusions made in the National CWS Assessment are 
justified by the underlying data.

[[Page 59663]]

    In the absence of this information, EPA is unable to substantiate 
the study conclusion that 75% of the permissible use areas have a 
carbofuran use intensity below 2.1 lbs a.i/mi\2\--even assuming that 
reliance on only 75% of the use areas would be protective, and nothing 
has been submitted to substantiate that conclusion. Use intensity maps 
that were provided with the Petitioners' comments appear to indicate 
that carbofuran use varies year by year, and it is not clear for which 
year or years, the Petitioners are relying to support their claim that 
use intensity will be below 2.1 lbs a.i/mi\2\. No further support for 
this claim was provided with the Petitioners' objections, even though 
EPA presented its conclusions in the final rule.
    As noted, the National CWS Assessment assumed that a use intensity 
below 2.1 lbs a.i/mi\2\ would assure that surface water concentrations 
will be below the level of concern. EPA agrees that using lower rates 
of carbofuran will result in lower exposure. But EPA does not agree 
that it has been demonstrated that a use intensity below 2.1 lbs a.i./
mi\2\ will assure that surface water concentrations will be below the 
applicable level of concern. The National CWS Assessment does not 
justify such a finding, nor has any other assessment that has been 
submitted to date. The Agency modeled use rates for carbofuran on corn 
based on the label proposed in September 2008, which are the rates at 
which farmers are legally allowed to apply carbofuran, and the results 
clearly demonstrate that estimated exposures will substantially exceed 
safe levels. The results of EPA's assessments are described in more 
detail in Unit V.E. of this order, the final rule and in Reference 111.
    EPA is equally unable to confirm the study's claim that the no-
application buffers on the September 2008 labels will adequately 
mitigate the risks ``in areas with historical use intensities greater 
than 2.1 lbs a.i./sq. mi.'' On the September 2008 labels, FMC included 
buffers of 300 feet on water bodies in Kansas, and 66 feet around water 
bodies in other places, but EPA cannot evaluate how these buffers 
relate to areas where carbofuran use intensities exceeded a specific 
value, for all of the reasons stated above. EPA did, however, model the 
effects from the buffers proposed on the September 2008 labels and 
found that these buffers reduce exposure by 5.1% (33.5 to 31.8 ppb) for 
corn in Kansas with a 300-foot spray drift buffer and 4.7% (29.9 to 
28.5 ppb) for corn in Texas with a 66-foot spray drift buffer. However, 
even with the buffers, EPA's analyses clearly demonstrate that 
estimated exposures will substantially exceed safe levels. These 
results are described in more detail in Unit V.E. of this order, the 
final rule, and Reference 84, Appendix I. For all of these reasons, the 
objection is denied.
    c. Objection/hearing request subissue: Challenges to EPA use of 
NAWQA monitoring data. The Petitioners object to EPA's discussion in 
the final rule of the extremely high concentrations detected in Zollner 
Creek in Oregon. They argue that reliance on these concentrations to 
confirm the results of EPA's modeling is not supportable because 
Zollner Creek is a small isolated creek, not a drinking water source, 
and that because of its size, is not representative of potential 
drinking water anywhere else. They also argue that the majority of the 
concentrations in the NAWQA data, including those detected at Zollner 
Creek, are extremely low--below the 1.1 ppb they claim is supported by 
their modeling. They also contend that the higher observed 
concentrations in the NAWQA monitoring data are the result of use 
patterns that are no longer permitted, and that allowed a much higher 
use rate than is currently permitted.
    i. Background. In the proposed rule, EPA described the available 
monitoring data that characterized carbofuran concentrations in surface 
water. EPA described that the highest concentrations of carbofuran are 
reported from a sampling station on Zollner Creek, which EPA 
acknowledged ``is not directly used as a drinking water source'' (73 FR 
44883). USGS monitoring at Zollner Creek from 1993 to 2006 detected 
carbofuran annually in 40-100% of the samples. EPA stated that although 
the majority of the concentrations detected were in the sub-part per 
billion range, concentrations have exceeded 1 ppb in 8 of the 14 years 
of sampling (Id.). The maximum measured concentration was 32.2 ppb, 
observed in the spring of 2002. EPA compared its modeling results to 
the concentrations seen in all of the USGS monitoring, Safe Drinking 
Water Act (SDWA) monitoring, and to the results of the available field 
scale studies. EPA concluded that the concentrations estimated in its 
modeling were consistent with the results of all of the available 
monitoring and studies (73 FR 44883-44884).
    In their comments on the proposed rule, the Petitioners alleged 
that comparisons between EPA's modeling concentrations and Zollner 
Creek detections were inappropriate because they were based on ``older 
data [that] are not reflective of future carbofuran use areas and/or 
intensities'' (Ref. 18 at 55). In support, they claimed that 
``carbofuran was once used at several nurseries and strawberry farms in 
the Zollner Creek watershed at estimated application rates of up to 15 
lbs. a.i./acre (5 times higher than the maximum rate on the current 
label, and 15 times higher than the most common use rates)'' (Id at 
56).
    In the final rule, EPA explained that it had not relied solely on 
Zollner Creek concentrations to validate its modeling. EPA again 
described the results of all available modeling, which included the 
detections at Zollner Creek, but also included results from all other 
NAWQA sites, SDWA post-treatment monitoring, and the results of field 
studies. Based on all of these data, EPA concluded that the results of 
the revised modeling conducted for the final rule was consistent with 
the available monitoring data.
    ii. Denial of hearing request. This subissue does not meet the 
standard for a hearing. The objections regarding Zollner Creek are not 
material. EPA did not rely in on the concentrations detected at Zollner 
Creek to provide significant support its assessment.
    In the final rule, EPA was clear that it considered the levels seen 
at Zollner Creek to be a rare circumstance:

    While available monitoring from other portions of the country 
suggests that the circumstances giving rise to high concentrations 
of carbofuran may be rare, overall, the national monitoring data 
indicate that EPA cannot dismiss the possibility of detectable 
carbofuran concentrations in some surface waters under specific use 
and environmental conditions.

(74 FR 23081). The final rule was clear that EPA placed greater 
reliance on the concentrations detected in Safe Drinking Water Act 
(SDWA) post-treatment monitoring, showing concentrations ranging 
between 4 and 7 ppb (74 FR 23079-23080). EPA also discussed the results 
of the UK tile drain studies as supplemental confirmation of its 
modeling (74 FR 23082).
    Petitioners' contentions regarding the NAWQA monitoring also fail 
to present a genuinely-disputed issue of material fact. In both the 
proposed and final rules, EPA acknowledged the large percentage of non-
detections and low concentration levels in the majority of the NAWQA 
monitoring data, and repeatedly explained the reasons that these data 
cannot serve as lower or upper bounds (73 FR 44882-44883; 74 FR 23081). 
Petitioners do not dispute those conclusions, or submit evidence to 
rebut them. When an objector does not challenge EPA conclusions in the 
final rule, but merely reiterates

[[Page 59664]]

comments made on the proposed rule, without submitting some evidence 
that calls EPA final rule conclusions into question, the objector has 
not raised a live controversy as to an issue material to the final 
rule. (See 73 FR 42700-42701 (denying hearing request where NRDC failed 
to object to the basis EPA asserted in its petition denial for 
rejecting their original challenge). Finally, no evidence has been 
submitted to support the contention that all of the higher 
concentrations exclusively result from uses or higher use rates that 
are no longer permitted. Hearings will not be granted on mere 
allegations (40 CFR 178.32(b)(2)).
    iii. Denial of objection. Data compiled in 2002 by EPA's Office of 
Water show that carbofuran was detected in treated drinking water at a 
few locations. Based on samples collected from 12,531 ground water and 
1,394 surface water source drinking water supplies in 16 states, 
carbofuran was found at no public drinking water supply systems at 
concentrations exceeding 40 ppb (the MCL). Carbofuran was found at one 
public ground water system at a concentration of greater than 7 ppb and 
in two ground water systems and one surface water public water system 
at concentrations greater than 4 ppb (measurements below this limit 
were not reported). Sampling is costly and is conducted typically four 
times a year or less at any single drinking water facility. The overall 
likelihood of collecting samples that capture peak exposure events is, 
therefore, low. For chemicals with acute risks of concern, such as 
carbofuran, higher concentrations and resulting risk is primarily 
associated with these peak events, which are not likely to be captured 
in monitoring unless the sampling rate is very high.
    Unlike drinking water derived from private ground water wells, 
drinking water from public water supplies (surface water or ground 
water source) will generally be treated before it is distributed to 
consumers. An evaluation of laboratory and field monitoring data 
indicate that carbofuran may be effectively removed (60-100%) from 
drinking water by lime softening and activated carbon; other treatment 
processes are less effective in removing carbofuran (Ref. 81). The 
detections between 4 and 7 ppb, reported above, represent 
concentrations in samples collected post-treatment. As such, these 
levels are of particular concern to the Agency. An infant who consumes 
a single 8-ounce serving of water with a concentration of 4 ppb, as 
detected in the monitoring, would receive approximately 130% of the 
aPAD from water consumption alone.
    To further characterize carbofuran concentrations in surface water 
(e.g., streams or rivers) that may drain into drinking water 
reservoirs, EPA analyzed the extensive source of national water 
monitoring data for pesticides, the USGS NAWQA program. The NAWQA 
program focuses on ambient water rather than on drinking water sources, 
is not specifically targeted to the high use area of any specific 
pesticide, and is sampled at a frequency (generally weekly or bi-weekly 
during the use season) insufficient to provide reliable estimates of 
peak pesticide concentrations in surface water. For example, 
significant fractions of the data may not be relevant to assessing 
exposure from carbofuran use, as there may be no use in the basin above 
the monitoring site. Unless ancillary usage data are available to 
determine the amount and timing of the pesticide applied, it is 
difficult to determine whether non-detections of carbofuran were due to 
a low tendency to move to water or from a lack of use in the basin. The 
program, rather, provides a good understanding on a national level of 
the occurrence of pesticides in flowing water bodies that can be useful 
for screening assessments of potential drinking water sources.
    The national monitoring data indicate that EPA cannot dismiss the 
possibility of detectable carbofuran concentrations in some surface 
waters under specific use and environmental conditions. Even given the 
limited utility of the available monitoring data, there have been 
relatively recent measured concentrations of carbofuran in surface 
water systems at levels above 4 ppb and levels of approximately 1 to 10 
ppb measured in streams representative of those in watersheds that 
support drinking water systems (Ref. 81). Based on this analysis, and 
since monitoring programs have not been sampling at a frequency 
sufficient to detect daily-peak concentrations that are needed to 
assess carbofuran's acute risk, the available monitoring data, in and 
of themselves, are not sufficient to establish that the risks posed by 
carbofuran in surface drinking water are below thresholds of concern. 
Nor can the non-detections in the monitoring data be reasonably used to 
establish a lower bound of potential carbofuran risk through this route 
of exposure. Nevertheless, these results are consistent with the 
results of EPA's surface water modeling (Refs. 12, 47, 67). For all of 
these reasons, the Petitioners objection is denied.
    d. Objection/hearing request subissue: New label restrictions and 
revised terms of registration. As discussed in Units VI.C and D, FMC 
submitted a request to amend its existing registration to incorporate a 
requirement intended to ensure that no more than 2% of any watershed 
will be treated with carbofuran. Petitioners allege that these new use 
restrictions will ensure that drinking water concentrations will not 
exceed 1.1 ppb. In support, the objection presents a June 30, 2009 
letter describing the restrictions, along with proposed revisions to 
the carbofuran labels.
    i. Background. On June 30, FMC requested that EPA amend its 
registration to incorporate a requirement that, within five days of 
applying the product, all applicators report to FMC the following 
information: the location that the product will be used; crop, use 
rate, application method, acreage, and quantity applied. Based on this 
information, FMC would track the percentage in each watershed. 
``Whenever it appears that carbofuran has been applied to 1.75% of any 
watershed,'' the registrant would report that information immediately 
to EPA, ``cease further sales in any county that overlaps with such a 
watershed for that use season, and shall attempt to recall all unused 
carbofuran within such counties by offering to repurchase such unused 
product'' (Exhibit 3). In addition, FMC requested that its registration 
be amended to require that ``based on watershed boundaries, FMC * * * 
prior to each uses season, allocate to its distributors in a manner 
which will attempt to ensure that no distributor receives more for 
carbofuran for sale than can be accommodated by the 2% watershed area 
cap in any watershed supplied by that distributor.''
    ii. Denial of hearing request. EPA denies this hearing request on 
two grounds. First, discussed in VI.C, Petitioners' objections and 
hearing requests are denied as irrelevant, and therefore immaterial, to 
EPA's determination in the May 15, 2009 final rule that the carbofuran 
tolerances were unsafe and could not be sustained under FFDCA section 
408. Petitioners are actually not objecting to the conclusions in EPA's 
final rule; rather, they are suggesting that EPA might reach a 
different result in a different factual scenario. Objections, however, 
must be directed ``with particularity [at] the provisions of the 
regulation or order deemed objectionable'' (21 U.S.C. 346a(g)(2)). 
Further, as discussed in Unit VI.D, this objection is untimely, because 
it was not raised in comments. Neither this specific proposal, nor any 
other proposal regarding a potential tracking system, was presented to 
EPA by the close of the September 29, 2008 comment period. EPA 
therefore

[[Page 59665]]

considers this issue waived, and will not consider this as an 
appropriate basis for justifying a hearing on its final rule.
    However, there is a further equally material defect in this hearing 
request. The Petitioners have submitted no evidence to support their 
allegation that these proposed requirements would be effective in 
ensuring that carbofuran would be applied to no more than 2% of any 
watershed. The only submission was the description provided in the June 
30 letter (Exhibit 3), and repeated above. However, this vague 
description leaves several critical questions unanswered. For example, 
the critical component of this proposal is a post-use reporting scheme, 
with a five-day delay between use and reporting. Even assuming that one 
accepts that reporting an address would allow for complete 
identification of the location within an individual watershed--a point 
on which no evidence has been submitted--no evidence, or even an 
explanation, has been provided to demonstrate how this after-the-fact 
reporting requirement will prevent application to greater percentages 
of the watershed. For smaller watersheds, as discussed in the final 
rule, application to only one or two farms may be sufficient to 
substantially exceed 2% of the watershed. In such cases, since 
applicators are only required to report within five days after 
application, it is likely that FMC would not be informed until after 
the 2% cap had been exceeded. Further, there will inevitably be some 
delay between FMC's attempt to repurchase the product and the reports 
suggesting (or confirming) that the cap either has been or will shortly 
be exceeded. Given the inevitable delay, it is not unlikely that 
further application would occur before FMC could even attempt to 
repurchase the product. No details whatsoever have been provided 
regarding the timing or mechanism by which this would occur. Further, 
this program operates in the absence of any enforceable use 
restriction, and no description of the means by which this would be 
enforced is provided. Although the company would ``attempt to recall 
the product'' or make it less available by ``attempting'' to direct 
sales to particular distributorships, in the absence of some mechanism 
to prevent sales or use, such as a permitting process, there is no real 
assurance that these voluntary measures would be effective (Exhibit 3). 
This is further complicated by the extremely low percentages 
contemplated by this proposal.
    Additionally, this scheme rests on a variety of assumptions that no 
evidence has been submitted to substantiate. For example, the proposal 
to restrict sales to distributors in particular watersheds rests on an 
assumption that farmers always purchase products from a distributor 
within their watershed. It also assumes that growers and distributors 
will accept FMC's offer to repurchase unused stock of the products, 
rather than seeking to stockpile the product for use in the next 
growing season.
    In the absence of any evidence to demonstrate the efficacy of these 
proposed restrictions, any objection based on these proposed amendments 
constitute no more than mere allegations or denials. Hearings will not 
be granted on such a basis (40 CFR 178.32(b)(2)).
    iii. Denial of objection. For the reasons discussed above, even if 
it were appropriate to consider the proposed registration amendments, 
EPA is unable to conclude that those amendments would ensure that 
concentrations of carbofuran in drinking water derived from surface 
water will not exceed 1.1 ppb. Accordingly, the objection is denied.
    e. Objection/hearing request subissue: Consistency with NMC surface 
water estimates. Petitioners object to EPA's surface water exposure 
estimates on the ground that they are inconsistent with the estimates 
EPA developed for purposes of the NMC CRA. Petitioners further claim 
that their revised surface water assessment is consistent with the EPA 
estimates in the NMC cumulative risk assessment. The evidence proffered 
for this objection consists of the modeling in Exhibit 15.
    i. Background. In comments on the proposed rule, the Petitioners 
complained that as part of the NMC CRA, EPA relied on actual ``county-
or multi-county level pesticide use information, based on agricultural 
chemical use surveys'' to develop its estimates of potential exposure, 
rather than assuming 100% PCT.'' In the final rule, EPA provided a 
lengthy and detailed explanation of the reasons that its approach to 
assessing individual chemicals and its approach to assessing the 
cumulative risks of multiple chemicals differed (74 FR 23067-23068 (May 
15, 2009)).
    ii. Denial of hearing request. To the extent Petitioners base this 
objection on the concerns raised in their comments, EPA denies the 
hearing request on this subissue because there is no disputed factual 
matter for resolution at a hearing. There is no dispute that EPA 
assumed 100% PCT for carbofuran in its surface water modeling, nor that 
EPA developed lower estimates in the NMC CRA, that accounted for the 
percent of the crop that was likely to be treated with each individual 
NMC chemical in order to more accurately account for the likelihood of 
pesticide co-occurrence at a single drinking water facility. Thus, the 
only question is whether EPA's basis for adopting a different approach 
between the assessment of a single chemical's aggregate exposure and 
the assessment of the cumulative exposures from several chemicals is 
reasonable. This question requires the application of a legal standard 
to undisputed facts. Hearings are not appropriate on questions of law 
or policy (40 CFR 178.32(b)(1)); (73 FR 42706-42707 (July 23, 2008)). 
FDA has repeatedly confirmed that the application of a legal standard 
to undisputed facts is a question of law for which a hearing is not 
required. (See, e.g., 68 FR 46403, 46406 n.18, 46408, 46409 (August 5, 
2003) (whether facts in the record show there is a reasonable certainty 
of no harm is a question of law; whether a particular effect is a 
``harm'' is a question of law)).
    In addition, Petitioners have not challenged the substance of EPA's 
response to their comments or submitted evidence that calls the 
substance of EPA's conclusions into question (40 CFR 178.32(b)(3)). 
Consequently, the Petitioners' objection on this issue is irrelevant, 
and therefore immaterial, with regard to EPA's final tolerance 
revocation regulation because Petitioners ignored EPA's extensive 
analysis of this issue in the final rule and essentially resubmitted 
their comments on the proposal as if EPA's determination in the final 
rule did not exist. The statute, however, requires that objections be 
filed on the final rule, not on the proposal (21 U.S.C. 346a(g)(2)). By 
ignoring the EPA's final rule on this subissue, Petitioners have failed 
to lodge a relevant objection. Both EPA and FDA precedent make clear 
that when the agency substantively responds to comments on the 
proposal, the commenter may only keep that issue alive in its 
objections by addressing the agency's substantive response. See 73 FR 
42698-42699 (When an objector does not challenge EPA conclusions in the 
section 408(d)(4)(iii) order but rather challenges some prior 
conclusion that was superseded by the section 408(d)(4)(iii) order, the 
objector has not raised a live controversy as to an issue material to 
the section 408(d)(4)(iii) order; 53 FR 53176, 53191 (December 30, 
1988) (where FDA responds to a comment in the final rule, repetition of 
the comment in objections does not present a live controversy unless 
the objector proffers some evidence calling FDA's conclusion into 
question)).

[[Page 59666]]

    To the extent this objection is simply an allegation that the 
results of the modeling are consistent with the surface water estimates 
in EPA's NMC risk assessment, the hearing request also suffers from a 
fatal flaw. The modeling is based on the assumption the recently 
proposed label restrictions are effective, and that the PCT will be 2%. 
Because the objection and hearing request are inextricably intertwined 
with the Petitioners' newly submitted proposed FIFRA registration 
amendments, the objection and hearing request are denied as irrelevant, 
as discussed in Unit VI.C. Further, as discussed, no evidence was 
submitted to support the assumption that the newly submitted use 
tracking proposal will be effective. The only evidence submitted in 
this regard is the results of the modeling in Exhibit 15, which as 
previously discussed is untimely, and therfore provides an 
inappropriate basis for a hearing. This evidence, therefore, on 
multiple grounds is insufficient to support a reasonable possibility 
that the issue will be resolved in the Petitioners' favor. No hearing 
is warranted under such circumstances (40 CFR 178.32(b)(2)).
    iii. Denial of objection. While it is true that in the NMC 
assessment EPA used PCT numbers to estimate the cumulative exposure 
from the contamination of such pesticides in surface water, this was 
done in order to more accurately account for the likelihood of 
pesticide co-occurrence at a single drinking water facility. But this 
does not mean that use of PCT is appropriate in conducting an 
assessment of aggregate exposure from carbofuran residues in surface 
water. This difference in approach between the assessment of a single 
chemical's aggregate exposure, and the assessment of the cumulative 
exposures from several chemicals, stems from the differences in the 
purpose and scope of the two assessments. These differences inevitably 
require the application of different methodologies.
    In evaluating the acute risks associated with a single chemical's 
contamination of drinking water, EPA must consider all of the 
variations permitted under the label. Drinking water exposures are 
driven by uniquely local factors; not only is the source of drinking 
water local (i.e., a person drinks water from his or her local water 
system, not from a combination of water systems from across the United 
States), but the likelihood and degree of contamination of any 
particular, local drinking water source, whether it is a reservoir or 
well, varies widely based on local conditions (e.g, from local pest 
pressures, weather). Given this local variability, EPA must evaluate 
how all of the practices permitted under the label will affect drinking 
water exposures, because all are legally allowed, and farmers may 
choose any of them based on their particular individual local 
conditions. This means that even if growers, on a national or regional 
basis, do not frequently use a particular practice, EPA must still 
evaluate whether aggregate exposures from that practice would be safe 
because the practice is legally permissible and may be used due to 
local conditions. Thus, for example, even if most growers tend to apply 
the chemical only to a portion of the field, or typically only apply 
one-half of the maximum application rate, EPA must determine whether 
use by all or some growers on the entire field or at the maximum rate 
in a local watershed would result in unsafe drinking water 
concentrations.
    By contrast, it is not feasible to conduct the identical analysis 
for a cumulative assessment of related chemicals. Since the potential 
combinations of variations in pesticide use practices for the group of 
pesticides to be assessed are essentially infinite, even with computer 
modeling it would be impossible to model or evaluate all of the 
combinations allowed under the labels. EPA therefore needed to narrow 
its evaluation of the possible combinations to those deemed ``likely'' 
to occur. In contrast to the single chemical assessment, a cumulative 
assessment is intended to develop a snapshot in time of what is likely 
occurring at the moment. Moreover, the purpose of a cumulative 
assessment is to identify major sources of risk that could potentially 
accrue due to the concurrent use of several pesticides that act through 
a common mechanism of toxicity. Thus, EPA is primarily interested in 
the subset of circumstances in which residues from such pesticides 
occur concurrently (or co-occur).
    In addition, one of the important attributes of a cumulative risk 
assessment is that its scope and complexity can potentially lead to 
inflated estimates of risk due to compounding conservatisms, which 
would reduce the interpretability and ultimately the utility of the 
assessments. Because many data sets need to be combined, reducing the 
impact and likelihood of compounding conservative assumptions and over-
estimation bias becomes very important in constructing a reasonable 
cumulative risk assessment.
    When little or no information is available to inform potential 
sources of exposure, such as a reasonable or maximum watershed scale 
PCT, it is both scientifically and legally reasonable for a single 
chemical assessment to incorporate conservative assumptions to reflect 
reasonable worst-case exposure estimates. But in a cumulative risk 
assessment, the incorporation of such conservative assumptions would 
imply multiple simultaneous reasonable worst-case exposure estimates 
for each individual chemical. This is so unlikely that the results 
would no longer represent even a reasonable worst-case estimate of the 
likely risks. Consequently, some of the conservative assumptions 
appropriately used in the single chemical risk assessments are not 
appropriate or reasonable for use in a cumulative risk assessment, and 
vice versa.
    As a result, EPA chose in the NMC to work with those data that most 
closely reflect ``representative'' exposures, and developed 
``representative'' estimates of PCT in regional watersheds. However, to 
be clear, the PCT values used in the NMC assessment do not represent 
estimates of 50% of watersheds, or even the ``average'' watershed; 
rather, they represent values that are expected to be as likely to be 
accurate as not, based on a random selection of watersheds. A 
comparable example is the statistic that the average American family 
has approximately 2 children; this may or may not be true for any 
individual family, but there is an equally good chance that it will be 
accurate for any randomly selected family, as that it will not be 
accurate. For the cumulative assessment, EPA is able accept this level 
of uncertainty in these estimates, precisely because it has confidence 
that aggregate exposures from the individual chemicals will be safe, 
based on the level of conservatism in the single chemical assessments. 
But given the statute's mandate to ensure a ``reasonable certainty of 
no harm,'' EPA could not rely on the approach used under the cumulative 
assessment in the absence of the more conservative single-chemical 
assessment that evaluates the full range of exposures permitted by the 
registration.
    Nevertheless, as discussed in the final rule, in response to FMC's 
concerns EPA performed a sensitivity analysis of an exposure assessment 
using a PCT in the watershed to determine the extent to which some 
consideration of this factor could meaningfully affect the outcome of 
the risk assessment. The results suggest that, even at levels below 10% 
CT, exposures from drinking water derived from surface waters can 
contribute significantly to the aggregate dietary risks, particularly 
for infants and children. Accordingly, these assessments suggest that 
use of a reasonably conservative PCT estimate,

[[Page 59667]]

even if one could be developed, would not meaningfully affect the 
carbofuran risk assessment, as aggregate exposures would still exceed 
100% of the aPAD.
    f. Objection/hearing request subissue: Natural surface water pH 
conditions. The Petitioners contend that the low PCT levels guaranteed 
by the recent proposed use tracking system, along with natural surface 
water pH conditions in the areas where use is permitted under the 
revised label will ensure potential exposures are de minimis. In 
support they reference the analysis in Exhibit 16, which they claim 
demonstrates that the NAWQA USGS data show that average surface water 
pH is above 7.5 and that ``in most regions, moving 2 standard 
deviations away from average (which would capture 95% of all observed 
values) results in pHs that are still greater than 7.5.''
    i. Background. In the proposed rule, EPA explained that the 
variation in pH across the landscape was a significant uncertainty in 
EPA's analysis. The proposal stated, that ``while it is well 
established that carbofuran will degrade at higher rates when the pH is 
above 7, and lower rates when below pH 7, due to the high variation of 
pH across the country for many of the scenarios, a neutral pH (pH 7) 
default value was used to estimate water concentrations (73 FR 44883). 
Petitioners raised no issue regarding surface water pH in their 
comments.
    ii. Denial of hearing request. EPA denies this hearing request 
because the objection, as well as the proffered evidence is untimely. 
EPA clearly described the potential impact that pH could have on its 
estimates, and noted that this was a significant uncertainty in its 
assessment. None of the analyses in Exhibit 16 were provided as 
comments on the proposed rule. Nor were any of the issues inherent in 
this objection raised as comments on the proposal. Since the proposed 
rule was clear that the issue was relevant, and the NAWQA data were 
available, Petitioners could have conducted these analyses and raised 
the issue as part of their comments. Consequently EPA has determined 
that the evidence submitted in support of this objection is not 
appropriately considered as a basis for justifying a hearing on its 
final rule. And in the absence of this evidence, the objection consists 
of mere allegations and general denials, which do not warrant a hearing 
(40 CFR 178.32(b)(2)). Further, to the extent the objection and the 
evidence in Exhibit 16 rely on use tracking system and risk mitigation 
proposals submitted as part of their objections, this hearing request 
is denied as irrelevant, and therefore immaterial, as discussed in Unit 
VI.C. Petitioners are actually not objecting to the conclusions in 
EPA's final rule; rather, they are suggesting that EPA might reach a 
different result in a different factual scenario. Objections, however, 
must be directed ``with particularity [at] the provisions of the 
regulation or order deemed objectionable'' (21 U.S.C. 346a(g)(2)). In 
addition, for the reasons discussed in Unit VI.D, any hearing request 
premised on the new mitigation measures is considered untimely, and not 
appropriately considered at this stage of the administrative process as 
a basis for granting a hearing under the FFDCA.
    EPA is also denying the requested hearing on the grounds that the 
evidence, even if established, is insufficient to justify the action 
urged (40 CFR 178.32(b)(3)). The analyses presented in Exhibit 16, as 
the Petitioners explicitly acknowledge, only capture 95% of the values; 
five percent of exposures are not, per se, de minimis. Second, just as 
with the groundwater pH analyses presented in Exhibit 14, no 
information was provided to explain how the samples relate to the state 
or other geographic area in which carbofuran would be used. This is 
important because NAWQA samples were not evenly distributed across most 
states, but tended to be concentrated in particular regions; in 
statistical parlance, the samples were not collected randomly. In other 
words, no evidence was provided that would allow the Agency to 
determine the percentage of the carbofuran use area represented by the 
95% of the samples the Petitioners' analysis addressed. Nor was any 
information provided to document the significance of the remaining 5% 
of the samples that were not captured by their analysis; for example, 
although this may have only represented 5% of the samples, it is not 
clear whether this 5% relates to only 5% of the areas where carbofuran 
may be used, or whether it actually represents a far greater percentage 
of the use area. Because this information, even if established, would 
provide an insufficient basis on which EPA could reasonably conclude 
that the drinking water exposures would be ``safe,'' this issue is not 
determinative.
    iii. Denial of objection. For the reasons presented above, the 
Petitioners' objection is denied. Further, there are several 
significant defects with the analysis in Exhibit 16. First, the 
analysis was based on statewide averages, which ignores the fact that 
pH is not evenly distributed, but randomly clustered. Second NAWQA 
contained no data for Kansas (KS), Oklahoma (OK), and South Dakota 
(SD); Petitioners simply assert that the ``given the similarity between 
these states and the other High Plains states, it is reasonable to 
extend the observations from Colorado (CO), Nebraska (NE), and North 
Dakota (ND)'' (Exhibit 16 at 4). Although the `High Plains' states all 
have extensive areas of grassland, they also have extensive geographic 
soil and climatic differences--e.g. the Black Hills and Badlands (SD), 
Sand Hills (NE), Flint Hills, Cheyenne Bottoms and Quivira wetlands 
(KS), Red Hills and Cross Timbers region (OK). These differences are 
not surprising since the distance from the Canadian border in ND to OK 
is over 1000 miles. Consequently it is not reasonable to extend 
observations from CO, NE, and ND to KS, OK, and SD.
    g. Objection/hearing request subissue: Effect of existing drinking 
water treatment systems. The Petitioners contend that a review of 
drinking water treatment systems in areas under revised labels 
indicates that the majority of the ``total population in affected 
states obtain their drinking water from surface water sources subject 
to lime softening or activated charcoal filters. They allege that ``60% 
of the total population in affected states'' will have their water 
treated by methods that will substantially reduce or entirely remove 
carbofuran concentrations. For the remaining 40%, they claim that a 
significant portion use ground water sources, which are already 
protected by the Petitioners' other mitigation measures, and the 
remainder are protected by the Petitioners' proposed use reporting 
scheme. In support of this objection, Petitioners rely on the analysis 
in Exhibit 17.
    i. Background. In the proposed rule, EPA explained that one of the 
more significant uncertainties in EPA's analysis was that EPA failed to 
account for the potential effect of treatment in removing carbofuran 
from finished drinking water before it is delivered to the consumer 
supply system. EPA explained that an evaluation of laboratory and field 
monitoring data indicate that carbofuran may be effectively removed 
(60-100%) from drinking water by lime softening and activated carbon; 
other treatment processes are less effective in removing carbofuran 
(Ref. 81). Although the Agency was aware of the mitigating effects of 
specific treatment processes, the processes employed at public water 
supply utilities across the country vary significantly both from 
location to location and throughout the year, and therefore EPA was 
unable to quantitatively incorporate this factor into its drinking 
water exposure

[[Page 59668]]

estimates. For example, lime softening would likely reduce carbofuran 
concentrations. That process is used in 3 to 21% of drinking water 
treatment systems in the United States (Ref. 14). Activated carbon has 
been shown to also reduce carbofuran concentrations, but is used in 1 
to 15% of drinking water treatment facilities (Id.). Petitioners noted 
this discussion in their comments, and relied on it to support their 
argument that their drinking water exposure assessments were 
conservative, because they did not account for the effect of treatment 
(Ref. 18 at 46-55). However they submitted no comments raising any of 
the issues or evidence presented in this objection.
    ii. Denial of hearing request. EPA denies this hearing request on 
the grounds that both the objection and the proffered evidence are 
untimely. EPA clearly described the potential impact that treatment 
could have on its estimates. None of the analyses in Exhibit 17 were 
provided as comments on the proposed rule. Nor were any of the issues 
inherent in this objection raised as comments on the proposal. Since 
the proposed rule clearly identified the issue, and the USGS data were 
available, the Petitioners could have conducted these analyses, or at 
least raised the issue, as part of their comments. Consequently, as 
discussed in Unit VI.D, EPA has determined that the evidence submitted 
in support of this objection is not appropriately considered as a basis 
for justifying a hearing on its final rule. In the absence of this 
evidence, the objection consists of mere allegations and general 
denials, which do not warrant a hearing (40 CFR 178.32(b)(2)). Further, 
to the extent the objection and the evidence in Exhibit 17 rely on the 
new registration proposals submitted in June 2009 as part of their 
objections, this evidence as well is deemed both immaterial and 
untimely. As discussed in Units VI.C and D, the new risk mitigation 
measures are not appropriately considered at this stage of the 
administrative process, and no hearing is warranted on this basis.
    EPA is also denying this hearing request on the grounds the 
Petitioners' evidentiary proffer is insufficient to justify the factual 
issue urged (40 CFR 178.32(b)(2)). The analysis in Exhibit 17 is based 
on the percentage of the total population across all states combined, 
not the percentage of the local populations served by an individual 
surface water source--or even the percentage within each state. Even 
assuming that the 60% figure could legitimately be translated to a 
state-by-state basis, their own analysis shows that some percentage of 
the population in individual states will remain unprotected. In 
Colorado, only 24% of the population obtains their drinking water from 
groundwater, and in Illinois, only 33% of the population obtains their 
drinking water from groundwater. Sixteen percent of Colorado's 
population is not de minimis. Consequently, even if the analysis were 
accurate, it would not provide a sufficient basis on which to conclude 
that exposures from drinking water would be ``safe.''
    A further consideration in this regard is that drinking water 
exposures are driven by uniquely local factors; not only is the source 
of drinking water local (i.e., a person drinks water from his or her 
local water system not from a combination of water systems from across 
the United States), but the likelihood and degree of contamination of 
any particular, local drinking water source, whether it is a reservoir 
or well, varies widely based on local conditions (e.g., from local pest 
pressures, weather). Examining a population across an entire state--let 
alone across several states--is an entirely inappropriate basis on 
which to conclude that drinking water exposures will be safe.
    The evidence submitted therefore does not support their contention 
that 60% of the population in ``affected states'' obtain their drinking 
water from public systems that use the treatment processes effective at 
mitigating carbofuran residues. For example, Exhibit 17 shows that a 
major Chicago surface water drinking water system, which serves a 
population of 9,000,000, has neither lime softening processes nor 
filters. Petitioners have submitted no evidence that this population is 
protected. The fact that a small population remains unprotected is not 
outweighed by the fact that a larger population in another community or 
state is protected. Their own evidence also shows that only 26 of 141 
of community water systems use lime softening/filters (Exhibit 17 at 4-
9), which supports the conclusion in the final rule that approximately 
20% facilities have appropriate treatment. See 57 FR 33244 (7/27/92) 
(Studies cited by NRDC do not provide a basis for the hearing because 
they ``support the [FDA] conclusion in question.''); 57 FR 6667 (2/27/
1992) (``A hearing must be based on reliable evidence, not on mere 
allegations or on information that is inaccurate and contradicted by 
the record.''); 49 FR 6672 (2/22/84) (no hearing if claim based on 
demonstrably false premise).
    iii. Denial of objection. For the reasons discussed above, this 
objection is denied. A further consideration is that treatment does not 
necessarily remove all residues. As previously noted, in both the 
proposed and final rules EPA discussed the SDWA monitoring detections 
between 4 and 7 ppb, which represent concentrations in samples 
collected post-treatment. As such, these levels are of particular 
concern to the Agency. An infant who consumes a single 8-ounce serving 
of water with a concentration of 4 ppb, as detected in the monitoring, 
would receive approximately 130% of the aPAD from water consumption 
alone. An infant who consumes a single 8-ounce serving of water with 
the higher detected concentration of 7 ppb, as detected in the 
monitoring, would receive approximately 220% of the aPAD from water 
consumption alone.

G. Objections to EPA's Dietary Risk Assessment

    Petitioners raise two related objections to the way in which EPA 
evaluated the aggregate dietary exposures to carbofuran residues. First 
they raise several technical challenges to the way in which EPA 
calculated the two recovery half-lives that were used in the risk 
assessment supporting the final rule to account for the potential for 
individuals to recover from the effect of ingesting carbofuran residues 
between exposures. Second, they object to the fact that in the final 
rule EPA included both aggregate exposure estimates that did not 
account for the potential for individuals to recover from the effects 
between exposures as well as estimates that did account for such 
recovery. In support the Petitioners cite to Exhibits 9 and 10. Exhibit 
9 is a memorandum prepared by Robert Sielken and Ciriaco Valdez-Flores. 
Exhibit 10 is a published literature study by Elsa Reiner that presents 
data on the rates of spontaneous reactivation of phosphorylated and 
carbamylated cholinesterases.
    1. Objection/hearing request subissue: Inclusion of exposure 
estimates that do not incorporate recovery in final rule. The 
Petitioners object to the fact that the final rule presented aggregated 
exposure estimates that did not incorporate the anticipated recovery 
from carbofuran's effects between exposures, in addition to those that 
did account for recovery. They claim that recovery time should be 
included in EPA's ``primary'' risk assessment.
    i. Background. As discussed in Unit V, EPA's standard acute dietary 
exposure assessment calculates total dietary exposure over a 24-hour 
period; that is consumption over 24 hours is summed and no account is 
taken of the

[[Page 59669]]

fact that eating and drinking occasions may spread out exposures over a 
day. This total daily exposure generally provides reasonable estimates 
of the risks from acute dietary exposures, given the nature of most 
chemical endpoints. Due to the rapid recovery associated with some 
chemical toxicity (e.g., AChE inhibition), 24-hour exposure periods may 
or may not be appropriate. To the extent that a day's eating or 
drinking occasions leading to high total daily exposure might be found 
close together in time, or to occur from a single eating event, minimal 
AChE recovery would occur between eating occasions (i.e., exposure 
events). In that case, the ``24-hour sum'' approach, which sums eating 
events over a 24-hour period, would provide reasonable estimates of 
risk from food and drinking water. Conversely, to the extent that 
eating occasions leading to high total daily exposures are widely 
separated in time (within 1 day) such that substantial AChE recovery 
occurs between eating occasions, then the estimated risks under any 24-
hour sum approach may be overstated. In that case, a more sophisticated 
approach--one that accounts for intra-day eating and drinking patterns 
and the recovery of AChE between exposure events--may be more 
appropriate. This approach is referred to as the ``Eating Occasions 
Analysis'' and it takes into account the fact that the toxicological 
effect of a first dose may be reduced or tempered prior to a second (or 
subsequent) dose.
    In the proposed rule, EPA conducted an Eating Occasion analysis 
based on two half-lives: 150 minutes and 300 minutes (73 FR 44887 (July 
31, 2008)). These half-lives were not specific to carbofuran, but were 
calculations derived for the NMC Cumulative Risk Assessment. EPA 
concluded that incorporating these analyses into the risk assessment 
had little impact on the risk estimates from exposures from food alone, 
but that risk estimates from combined exposures from food and water 
were reduced by approximately 2-3X (Id). However, because many of EPA's 
risk concerns stemmed from a single exposure (e.g., one meal) and 
because, even when recovery was accounted for, aggregate exposures far 
exceeded safe levels, EPA concluded that ``risks to carbofuran is 
indeed not substantively overestimated using * * * the 24-hour 
approach'' (Id).
    In their comments, Petitioners complained that EPA had failed to 
incorporate recovery into their risk assessment. They further argued 
that EPA should calculate the per capita 99.9th percentile based on all 
person minutes rather than all person-days. In addition, they submitted 
an aggregate dietary risk assessment they had conducted using a 150-
minute half-life input. They submitted no explanation for using only 
the 150-minute half-life rather than also including estimates based on 
the 300-minute half-life that EPA has used for the proposed rule.
    In the final rule EPA explained that it had conducted a revised 
Eating Occasion analysis to evaluate the impact of carbofuran's rapid 
reversibility on its risk estimates (74 FR 23086 (May 15, 2009)). EPA 
concluded that incorporating Eating Occasion Analysis and the 186-
minute or 426-minute recovery half-lives for carbofuran did not 
significantly change the risk estimates for food exposures alone (74 FR 
23086 (May 15, 2009)). EPA concluded that risk estimates based on 
combined food and drinking water exposures are reduced considerably--by 
a factor of two or more in some cases, but nonetheless still 
substantially exceed EPA's level of concern for infants and children. 
EPA also explained that the Agency remains concerned about the risks 
from single eating or drinking events. Finally, EPA noted that the 
Eating Occasion Analyses underestimate exposures to the extent that 
they do not take into account carry-over effects from previous days, 
and because drinking water concentrations are randomly picked from the 
entire 30-year distribution (Id at 23087).
    ii. Denial of hearing request. EPA is denying this hearing request 
on two grounds. First, the objection fails to present a disputed issue 
of material fact. The record is clear that EPA did incorporate recovery 
into its analysis; indeed, one of Petitioners' objections relates to 
the manner in which EPA incorporated recovery into its risk assessment 
(Obj at 30-33). Rather, their only challenge is that the final rule 
should have only presented risk estimates that accounted for recovery. 
The sole issue is whether it was reasonable for EPA to have also 
communicated aggregate risks that did not account for recovery, when 
(1) EPA's estimates showed that accounting for recovery demonstrated 
that EPA's standard 24-hour estimates were not substantially 
overstated; (2) EPA's approach to accounting for recovery 
underestimates some risks; and (3) EPA's risk assessments concluded 
that infants received unsafe exposures from a single meal (eating 
occasion). This is a policy issue, and hearings are not appropriate on 
such (40 CFR 178.32(b)(1)).
    Second, the fact that EPA relied on 24-hour aggregate exposures in 
addition to analyses that accounted for recovery is not material. As 
documented in the final rule, EPA would still have concluded that 
revocation of all tolerances were warranted on the grounds that, even 
accounting for recovery, aggregate exposures are not ``safe.'' Even 
though accounting for recovery resulted in a 2-3X reduction in exposure 
estimates, many of EPA's estimates for aggregate exposures ranged 
between 2700% aPAD and 9400% aPAD for infants. Accounting for recovery 
does not, therefore, demonstrate that aggregate exposures will be safe 
for infants. Of greater significance in this regard is EPA's finding 
that infants are at risk from a single exposure. Recovery is only 
relevant, by definition, where the risk is derived from multiple 
exposures over time.
    iii. Denial of objection. The reason for not simply adopting the 
assessment incorporating recovery time was that the Agency has concerns 
that other aspects of its exposure model tends to understate exposure. 
If the assessment using recovery time had suggested that carbofuran 
risks may be acceptable, EPA would have had to further examine how 
exposure was assessed. However, because both the assessment based on 
24-hour exposure and the one incorporating recovery time showed 
carbofuran exposures to be well over the safe level, EPA concluded that 
its exposure assessment was reasonable. As explained in the final rule, 
incorporating Eating Occasion Analysis and the 186-minute or 426-minute 
recovery half-lives for carbofuran resulted in a reduction in the risk 
estimates for which food and drinking water are jointly considered 
(i.e., Food + Drinking Water) by a factor of two or more in some cases. 
But even though the risk estimates from aggregate exposure are reduced, 
they nonetheless still substantially exceed EPA's level of concern for 
infants and children. Using drinking water derived from the surface 
water from the Idaho potato surface water scenario, which estimated one 
of the lowest exposure distributions, aggregate exposures at the 99.9th 
percentile ranged from 328% of the aPAD under the scenario for which 
infants rapidly metabolize carbofuran (e.g., 186-minute half-life), to 
a high of 473% of the aPAD under the scenario for which infants 
metabolize carbofuran more slowly (e.g., scenarios in which a 426-
minute half life is assumed). Either way, the tolerances are unsafe.
    Moreover, even accounting for the estimated decreased risk from 
accounting for carbofuran's rapid reversibility, for which recovery 
between exposures is irrelevant. The Agency remains concerned about the

[[Page 59670]]

risks from single eating or drinking events, as illustrated in the 
following example, based on an actual food consumption diary from the 
CSFII survey. A 4-month old male non-nursing infant weighing 10 kg is 
reported to have consumed a total of 1,070 milliters (ml) of indirect 
water over eight different occasions during the day. The first eating 
occasion occurred at 6:30 a.m., when this 4 month old consumed 8 fluid 
ounces of formula prepared from powder. The FCID food recipes indicate 
that this particular food item consists of approximately 87.7% water, 
and therefore, 8 ounces of formula contains approximately 214 ml (or 
grams) of indirect water; with the powder (various nutrients, dairy, 
soy, oils, etc.) accounting for the remaining 12.3%. This infant also 
reportedly consumed a full 8-ounce bottle of formula at 12 p.m., 4 
p.m., and 8 p.m. that day. The food diary also indicates that the 
infant consumed about 1 tablespoon of water (14.8 ml) added to prepare 
rice cereal at 10 a.m., about 2 ounces of water (59.3 ml) added to pear 
juice at 11 a.m., another \1/2\ tsp of water (2.5 ml) to prepare more 
rice cereal at 8:30 p.m.; and finally, he consumed another 4 ounces of 
formula (107 ml) at 9:30 p.m.
    The infant's total daily water intake (1,070 ml, or approximately 
107 ml/kg/day) is not overly conservative, and represents substantially 
less than the 90th percentile value from CSFII on a ml water/kg 
bodyweight (ml/kg/bw) basis. As noted, carbofuran has been detected in 
finished water at concentrations of 4 ppb. For this 10 kg body weight 
infant, an 8-ounce bottle of formula prepared from water containing 
carbofuran at 4 ppb leads to drinking water exposures of 0.0856 
micrograms of active ingredient/kilogram of bodyweight ([mu]g ai/kg 
bw), or 114% of the aPAD from that bottle alone. Based on the total 
daily water intake of 1,070 ml/day (no reversibility), total daily 
exposures from water at 4 ppb concentration would amount to 0.4158 
[mu]g ai/kg bw, or 555% of the aPAD; this is the amount that would be 
used for this person-day in the Total Daily Approach.
    Peak inhibition occurs following each occasion on which the infant 
consumed 8 fluid ounces of formula (6 a.m., 12 p.m., 4 p.m. and 8 
p.m.); however, the maximum persisting dose occurs following the 9:30 
p.m. eating occasion, based on a 186-minute half-life parameter. This 
produces a maximum persisting dose of 0.1457 [mu]g ai/kg bw, or about 
30% of the total daily exposure of 0.4158 [mu]g ai/kg bw derived above, 
or expressed as a fraction of the level of concern, the maximum 
persisting dose amounts to about 194% of the aPAD (or 30% of 554%). 
Note that with drinking water concentration at 4 ppb, an infant 
consuming one 8 oz bottle of formula--prepared from powder and tap 
water containing carbofuran at 4 ppb will obtain exposures of 
approximately 114% of aPAD. Since many infants consume the equivalent 
of this amount on a single eating occasion, accounting for 
reversibility over multiple occasions is not essential to ascertain 
that infants quite likely have obtained drinking water exposures to 
carbofuran exceeding the level of concern based on drinking water 
concentrations found in public drinking water supplies.
    The approach discussed above is used to evaluate the extent to 
which the Agency's 24-hour approach to dietary risk assessment 
overestimates risk from carbofuran exposure. The results of both 
approaches indicate that the risk from carbofuran is indeed not 
substantively overestimated using the current exposure models and the 
24-hour approach.
    In this regard, it is important to note EPA's Eating Occasion 
Analyses underestimate exposures to the extent that they do not take 
into account carry-over effects from previous days, and because 
drinking water concentrations are randomly picked from the entire 30-
year distribution. As discussed previously, DEEM-FCID is a single day 
dietary exposure model, and the DEEM-based Eating Occasion Analysis 
accounts for reversibility within each simulated person-day. All of the 
empirical data regarding time and amounts consumed (and corresponding 
exposures based on the corresponding residues) from the CSFII survey 
are used, along with the half-life to assess an equivalent persisting 
dose that produced the peak inhibition expected over the course of that 
day. This is a reasonable assumption for food alone; since the time 
between exposure events across 2 days is relatively high (compared to 
the half-life)--most children (>9 months) tend to sleep through the 
night--and the time between dinner and breakfast the following morning 
is long enough it is reasonable to ``ignore'' persisting effects from 
the previous day. A single day exposure model will underestimate the 
persisting effects from drinking water exposures (formula) among 
infants, and newborns in particular (<3 months), since newborns tend to 
wake up every 2 to 4 hours to feed. Any carry over effects may be 
important, especially if exposures from the previous day are relatively 
high, since the time between the last feeding (formula) of the day and 
the first feeding of the subsequent day is short. A single day model 
also does not account for the effect of seasonal variations in drinking 
water concentrations, which will make this effect more pronounced 
during the high use season (i.e., the time of year when drinking water 
concentrations are high). Based on these analyses, the Agency concludes 
that the current exposure assessment methods used in the carbofuran 
dietary assessment provide realistic and high confidence estimates of 
risk to carbofuran exposure through food and water.
    In summary, there are several factors that may cause EPA's 
exposure/risk model to either understate or overstate exposure/risk. It 
is unreasonable to present risks only incorporating factors that tend 
to reduce exposure/risk estimates (e.g., recovery time), as Petitioners 
suggest. EPA's approach of evaluating the impact that these factors may 
have on the risk assessment is an appropriate method of taking all 
relevant factors into account. Petitioners' objection to EPA's policy 
decision to present acute risks in terms of 24-hours of exposure is 
therefore denied because EPA's policy approach here is reasonable.
    2. Objection/hearing request subissue: Technical challenges to 
EPA's calculated half-lives. Petitioners contend that EPA's calculation 
of carbofuran half-lives of 186 minutes and 426 minutes were flawed, 
and that the data instead support the use of a 150-minute half-life. 
Petitioners identify three specific challenges: (1) Because one of the 
time course studies showed that the time-to-peak effect was one hour, 
EPA's assumption that the time-to-peak effect in each study was 15 
minutes is incorrect; (2) EPA included the control rats in its 
modeling, which distorts the estimated recovery half-life because it 
incorporates AChE from animals that were not dosed and did not need to 
recover; (3) Biochemically, the recovery half-lives of all NMC 
chemicals should be the same, which supports the use of a 150-minute 
half-life. In support of these claims, Petitioners offered a summary of 
written testimony from Drs. Sielken and Valdez-Flores (Exhibit 9) and a 
published study (Exhibit 10).
    i. Background. In the proposed rule, EPA relied on half-lives of 
150 minutes and 300 minutes (73 FR 44887). These values were calculated 
for the NMC cumulative risk assessment and so were intended to 
encompass the half-lives for all of the NMC pesticides.
    In the final rule, EPA calculated half-lives specific to carbofuran 
to ensure that its analyses accurately reflected carbofuran's risk. 
Using the two FMC

[[Page 59671]]

time course studies in rat pups EPA calculated half-lives for recovery 
of 186 and 426 minutes (Id). The two values were derived from two 
different studies using rat pups of the same age (Refs. 24, 25); the 
two values provide an indication that half-lives to recovery can vary 
among juvenile rats. By extension, children are expected to vary in 
their ability to recover from AChE inhibition where longer recoveries 
would be associated with a potentially higher ``persisting dose.''
    ii. Denial of hearing request. The issue of the appropriate half-
lives for carbofuran is not material. Petitioners have proffered no 
evidence to show that reliance on a 150-minute half-life rather than a 
186-minute half-life would make a significant difference to their 
estimates. By contrast, in the risk assessment supporting the final 
rule, EPA's estimates show that the use of a 150-minute or 186-minute 
half-life makes little or no difference. For example, EPA's estimated 
exposures from food alone for children 1-2 were 43% of the aPAD, 
assuming a 186-minute half-life, and 41% of the aPAD, assuming a 150-
minute half-life. Similarly, for infants, the estimates ranged from 31% 
aPAD, assuming a 186-minute half-life, and 30% of the aPAD, assuming a 
150-minute half-life. For all other age groups, the estimated exposures 
were identical, whether one assumed a 150-minute or 186-minute half-
life.
    In any event, Petitioners' objection would have ultimately no 
effect on the Agency's conclusion that the carbofuran tolerances are 
not ``safe.'' Given EPA's assessments showing that a single exposure 
can result in excessive risks to infants--a conclusion that Petitioners 
have not challenged--the extent of recovery between subsequent 
exposures is irrelevant. This conclusion alone provides an adequate 
basis to revoke the carbofuran tolerances. Accordingly, because the 
action would be the same even if the factual issue were resolved in the 
manner sought, this request does not meet the standard for granting a 
hearing (40 CFR 178.32(b)(3)).
    There is yet a further consideration affecting the materiality of 
this objection. EPA's recalculation of half-lives in the final rule 
would ordinarily mean that Petitioners could appropriately challenge 
EPA's methodology for deriving the revised half-lives for the first 
time in their objections. This is because the Petitioners would have 
had no prior opportunity to challenge the manner in which these 
estimates were developed, as EPA had not previously relied on 
carbofuran-specific estimates. However in this case, the Petitioners 
never commented on the 300-minute estimate EPA used in the proposal, 
nor raised any issue to challenge the reliance on a longer half-life to 
account for the variation in children's sensitivity. For the reasons 
discussed in Unit VI.D, they have therefore waived any objection to use 
of a 300-minute half-life. Accordingly, the question of whether the 
Petitioners' half-life of 150-minutes or EPA's estimated half-life of 
186-minutes is immaterial, since the lower amount of recovery 
associated with the longer 300-minute half-life would be expected to 
have a far greater impact than the use of a 186-minute half-life.
    EPA is also denying the hearing request because the evidentiary 
proffer in support of this objection is inadequate. Petitioners have 
not provided the underlying analyses conducted in support of their 
calculated half-lives. The remainder of Exhibit 9 consists of 
contentions that EPA's analyses were mistaken. In the absence of the 
analyses that support their claim that the data support a half-life of 
150 minutes, Petitioners' evidentiary proffer consists of no more than 
mere allegations and denials. Hearings will not be granted on this 
basis (40 CFR 178.32(b)(2)) (See 73 FR 42706 (July 23, 2008) (``NRDC 
does no more than state `[w]e are aware of no statistical test' which 
would support EPA's use of the Gledhill data. As EPA's regulations make 
clear, a mere `denial' of an EPA position is not sufficient to satisfy 
the standard for granting a hearing'') (citations omitted); 53 FR 
53176, 53199 (December 30, 1998) (``Rather than presenting evidence 
[the objector] asserts that FDA did not adequately justify its 
conclusions. Such an assertion will not justify a hearing.'').
    The published paper in Exhibit 10 does not cure this defect. The 
paper was submitted to support the claim that the Petitioners' 150-
minute half-life is consistent with the ``available literature on the 
AChE recovery'' (Obj at 32). This evidence is immaterial. The Reiner 
paper relates to the reactivation of the AChE enzyme; however the 
relevant issue is not the reactivation of the cholinesterase enzyme, 
but the level of chemical in that target tissue, which this study does 
not address. Moreover, this study concludes that ``[I]t follows from 
the data in Tables 1 and 2 that the rate of spontaneous reactivation 
cannot be predicted, but must be separately determined for each 
compound and each enzyme source (Exhibit 10 at 1). The paper did not 
include data specifically on carbofuran, and it is therefore difficult 
to see how this could be argued to support the Petitioners' half-life 
of 150-minutes.
    iii. Denial of objection subissue. All of Petitioners' claims are 
incorrect.
    Appropriate time to peak effect. The Petitioners claim that the 
time to peak effect in the study with MRID 47143704 (Ref. 2) should 
have been 1 hour instead of the 15 minutes EPA calculated. Petitioners 
chose this value simply by choosing the data point with the highest 
level of inhibition. But this approach is flawed in a number of 
regards: First as a practical matter, using the same criteria on which 
the Petitioners rely, the time to peak effect in MRID 46688913 (Ref. 3) 
is 15 minutes. Petitioners have presented no basis for excluding those 
results.
    More significantly, the Petitioners' approach fails to account for 
the variability of the estimated AChE activity at each time point. As a 
point of background, the level of the highest inhibition is not 
something that can be observed, in the way that motor activity is 
observed. To determine inhibition, samples are taken and measured--the 
samples may or may not capture the highest point of inhibition; the 
technician has not external indicia that will determine the moment of 
the ``peak.'' Determining peak inhibition is estimated based on the 
available measurements. But because measurements are generally 
variable--the animals differ and the sampling itself is not identical, 
as people cannot perfectly replicate their actions time after time--in 
order to accurately capture the peak levels, the variability needs to 
be accounted for. When, as here, the individual values are quite 
variable, then for a half-life as long as carbofuran's, the sampling 
variability will make the study means bounce up and down around a trend 
line representing the true recovery rate. Figure 2 illustrates the 
sampling variability of the measured AChE activity and its relationship 
to EPA's modeling estimates for PND11 pups. In brief, this plots 
observed versus predicted for all the data. Each little point is an 
individual animal, while the time-group mean is the larger version of 
the same plotting symbol. The vertical lines are the 95 percent 
confidence intervals for each mean, the vertical lines. The diagonal 
line in each figure is the identity line--i.e., the line all the data 
would fall on if there were no variability and the model were perfect. 
Normally, one would expect some random scatter about the identity line. 
In such a case, simply visually picking the time with the lowest mean, 
which is what the Petitioners have done, will

[[Page 59672]]

not be a very reliable way to estimate the time to peak effect.
[GRAPHIC] [TIFF OMITTED] TR18NO09.001

    Inclusion of data from control animals. It is standard scientific 
practice to include concurrent control animals (i.e., animals that are 
not dosed with the test substance) as part of any experimental design. 
The purpose of controls is to determine the effects of the inevitable, 
unexpected, and uncontrolled variations in experimental practice, such 
as the biological variation between individual living animals. EPA's 
model simply used control levels to establish a baseline against which 
to evaluate the recovery of the treated animals. For example, as 
discussed above, measurements of AChE activities may change, and that 
concurrent controls are set up so that the same non-dose-related 
factors that affect treated animals will also affect control animals. 
Thus, EPA measured activity and computed inhibition based on measures 
of activity in treated animals and concurrent control animals. Thus, if 
the control animals showed that measured levels of AChE typically 
varied by 5 percent, if the dosed animal showed inhibition levels of 20 
percent, EPA would consider that only 15 percent of the inhibition 
would be related to the chemical exposure. EPA did not estimate a half-
life of recovery for the control animals and incorporate that into the 
estimated half-lives, which seems to be the Petitioners' allegation.
    Biochemically, the recovery half-lives of all NMC chemicals should 
be the same. Although the Petitioners' claim that the recovery rate of 
AChE inhibited by carbamate compounds is dictated by the commonly-
shared NMC carbamyl group is theoretically plausible, in reality, it is 
not supported by the data on the NMC compounds. EPA had originally 
hoped, based on the same mechanistic argument Petitioners make, that 
half-lives would be the same across all NMCs, thus greatly simplifying 
the cumulative risk assessment. It turned out, though, in the NMC data 
sets analyzed for the NMC cumulative risk assessment, that estimated 
recovery half-lives changed (generally, they got longer) as dose 
increased, which is counter to the results that would be predicted from 
the Petitioners' simple mechanistic argument (Ref. 81). Ultimately, 
this is due to the fact that the relevant question is not the abstract 
reactivation of the cholinesterase enzyme, but the level of chemical in 
the living animal's target tissue, which is a function both of the 
pharmacokinetics of the NMC (i.e., the rate at which the chemical is 
absorbed, distributed among tissues, and eliminated) in the animal and 
the rate of hydrolysis of the leaving group off the AChE molecule. 
These parameters vary at least somewhat for the different carbamates, 
accounting for the differences in half-lives between the NMC 
pesticides.

H. Objection to EPA's Decision Not To Rely on Carbofuran Human Study

    Petitioners object to EPA's reliance on a default 10X interspecies 
factor, which accounts for the uncertainties inherent in extrapolating 
from animal data to the anticipated effects in humans. They argue, for 
several reasons, that EPA should have instead used a 3X interspecies 
factor. All of their arguments, however, depend on EPA consideration of 
an oral carbofuran dosing study conducted in humans. EPA did not rely 
on the cited human study because it found, taking into account the 
advice of the HSRB, that the study was scientifically invalid. EPA's 
Human Research rule prohibits EPA from considering scientifically 
invalid human studies (40 CFR 26.1701). In their objections, 
Petitioners argue that the HSRB's, and presumably EPA's, evaluation of 
the scientific validity of the human study was flawed because (1) the 
human study was not considered in light of the animal data on 
carbofuran; (2) insufficient weight was given prior independent reports 
on the value of the Arnold study which reached the opposite conclusion 
from the HSRB; (3) the ``technical'' concerns raised by the HSRB are 
addressed by ``the data within the study'' and that these ``technical'' 
deficiencies do not render the Arnold study unreliable.
    1. Background. There are three intentional dosing human studies 
conducted with carbofuran that were conducted by J.D. Arnold in 1976, 
1977, and 1978. One study was an oral ingestion toxicity study and two 
studies were intended to evaluate toxicity from dermal exposure (Refs. 
7, 8, 9). The oral study conducted with carbofuran was carried out in 
nine healthy male

[[Page 59673]]

volunteers using an ascending dose schedule and single doses of 0.05, 
0.1 and 0.25 mg/kg (Ref. 7). The two dermal toxicity studies were found 
to have significant ethical deficiencies and the EPA's Human Studies 
Review Board recommended against their use. The Petitioners do not 
challenge the decision to disregard these studies.
    As previously noted, EPA did not rely upon any of the existing 
intentional dosing human toxicity study deriving an acceptable level of 
exposure for carbofuran. Instead, EPA relied on data conducted with 
rats, and applied the default 10 x interspecies factor to account for 
the potential uncertainty in extrapolating from animal data. EPA's 
decision not to rely on the Arnold studies was made pursuant to its 
Human Research rule. As explained in Unit III.B, that rule establishes 
different ethical standards for the review of completed human studies 
depending on whether they were initiated before or after the effective 
date of the rule on April 7, 2006. For an intentional human exposure 
study such as the Arnold studies, that was initiated prior to April 7, 
2006, EPA is barred, subject to a very limited exception, from relying 
on it if there is clear and convincing evidence that the conduct of the 
research was fundamentally unethical or significantly deficient with 
respect to the ethical standards prevailing at the time the research 
was conducted (40 CFR 26.1704, 26.1706). Further, the rule limits the 
human research that can be relied upon by EPA to ``scientifically valid 
and relevant data'' (40 CFR 26.1701). Finally, because the Arnold study 
was conducted with the purpose of identifying or measuring a toxic 
effect, EPA is required by the rule to submit its determination 
regarding these issues to an independent expert advisory body known as 
the Human Studies Review Board (``HSRB'') for review. These procedures 
were followed with regard to the Arnold study.
    The HSRB reviewed the Arnold oral and dermal carbofuran human 
studies at its May, 2006 meeting (Refs. 7, 8, 9). The Board found 
numerous technical deficiencies regarding the conduct of the oral study 
and that overall, the weaknesses of the studies far outweigh the 
strengths. These deficiencies included: (1) There was no justification 
or rationale for the selection of doses used in any of the three 
studies. (2) The sample size was very small (typically two subjects per 
dose or condition) with few or no controls (no more than two control 
subjects in any study). Such a design prevented evaluation of 
statistical significance for any parameter measured in the studies. (3) 
The values obtained for RBC and plasma cholinesterase levels were 
highly variable. Factors that contributed to this variability included 
the small sample size, the inclusion of only a single baseline sample 
collected immediately prior to dosing used to compare all post-dosing 
samples, the small number of control subjects, and an uncommon method 
for analytical determination of cholinesterase activities. The 
contribution of potential laboratory error cannot be ruled out. (4) 
Plasma cholinesterase levels were highly variable in all studies so as 
to preclude any useful interpretation. In general, plasma 
cholinesterase levels were not consistent with changes in RBC 
cholinesterase activities. (5) One subject who presented with abnormal 
vestibular mechanisms in the pre-dose evaluation was used in the oral 
study and showed serious symptoms after treatment. (6) Subjects were 
allowed to smoke during the study period.
    In response to a specific request from the Agency, the Board 
provided additional analysis concerning the potential for the data in 
human subjects for carbofuran to be applied to: (1) The calculation of 
a benchmark dose (BMD10) and identification of the 
BMD10L (lower confidence limit); (2) the identification of a 
NOAEL or LOAEL for effects or (3) the comparison to other species for 
possible adjustments to uncertainty factor for the cumulative 
assessment. The HSRB provided the following additional perspective 
relative to the Agency's question:

    The utility of the human studies with carbofuran was limited by 
the very small sample size used in all of the studies. The Agency 
proposed to use the RBC cholinesterase data for determination of the 
BMDL10. However, under conditions where the group size 
was only two, it would be imperative to have highly accurate, valid, 
reliable and consistent measures of RBC cholinesterase activity in 
both control and carbofuran-treated subjects. This rigor was simply 
not achieved in the human studies. Rather, RBC cholinesterase 
activities were compared to a single baseline value, were highly 
variable across subjects, including controls, and did not show any 
consistency with plasma cholinesterase levels. As such, although EPA 
scientists calculated a BMDL10 from the time course of 
changes in RBC cholinesterase values in the nine subjects evaluated 
in the oral study, the HSRB concluded that the accuracy and 
reliability of this calculation was limited by the technical 
shortcomings noted for the study. Therefore, the HSRB reiterated its 
recommendation that the BMDL10 calculated by the Agency 
from the human data should not be used.
    In a similar manner, the small sample size, compounded by the 
lack of consistent changes in cholinesterase activities in all 
studies, the inappropriate methods used for dermal application of 
the compound in the dermal studies and the inclusion of at least one 
subject who presented with abnormal vestibular function in a pre-
dose assessment limited the general utility of the data. 
Collectively, the weaknesses in the conduct and outcomes of the 
carbofuran human studies cast doubt on the utility of the data for 
identifying a NOAEL or LOAEL or for comparing across species in 
consideration of the interspecies uncertainty factor for the 
cumulative risk assessment. Thus the majority of HSRB members agreed 
the human oral data should not be used to identify a NOAEL or LOAEL, 
and there was unanimous agreement that the human dermal data should 
also not be used for these evaluations.

    The HSRB concluded that while these studies were informative, due 
to the numerous technical issues regarding the conduct of the oral 
study, overall, the weaknesses of the studies far outweigh the 
strengths. Describing the studies as ``poor science,'' the HSRB 
recommended against the use of the oral study conducted with carbofuran 
in human subjects for the single chemical assessment or in informing 
the interspecies uncertainty factor for the cumulative assessment.
    In their comments opposing EPA's proposal to revoke carbofuran 
tolerances, Petitioners essentially raised the same arguments they 
present in their objections.
    In responding to Petitioners' comments, EPA explained that it 
agreed with the HSRB's conclusions that the studies were scientifically 
flawed, and that, therefore, under the Human Research rule, EPA was 
barred from considering them (Ref. 85 at 9).
    2. Denial of hearing request. The critical issue here is EPA's 
determination under the Human Research rule that the Arnold study was 
scientifically invalid. All of Petitioners' arguments concerning the 
choice of the interspecies safety factor rely on EPA's consideration of 
the Arnold study. As noted above, Petitioners make three arguments as 
to why EPA erred in its determination. For the reasons discussed below, 
none of those arguments satisfy the regulatory standard for granting a 
hearing. Further, as explained in Unit VI.H.3., Petitioners' objections 
to EPA's determination have no merit. Thus, there is no need to 
consider Petitioners' more general arguments about EPA's decision to 
use a 10X interspecies factor in assessing carbofuran's risk.
    Petitioners' first argument as to why EPA erred in its 
determination that the Arnold study was scientifically invalid is that 
EPA failed to consider the animal data on carbofuran in assessing the 
scientific quality of the Arnold study. This claim is not material and 
thus not

[[Page 59674]]

appropriate for a hearing (40 CFR 178.32(b)(3)). Under the Human 
Research Rule, the relevant question is whether the Arnold study is 
scientifically valid, not whether consideration of the Arnold study in 
conjunction with the animal data could justify a lower interspecies 
factor. EPA, and the HSRB, found the Arnold study to be flawed at its 
core--due primarily to its small sample size and the high variability 
in measurement of AChE inhibition--and no amount of data from other 
studies in animals can cure these defects in the Arnold study. Thus, 
Petitioners' claim here is irrelevant and immaterial to EPA's decision. 
Ultimately, Petitioners' objection is a challenge to the policy 
established in the Human Research rule that EPA will not routinely 
consider all human data. They contend that ``[s]ince [human] data exist 
for carbofuran, they should have been used to select the interspecies 
uncertainty factor.'' However, this policy question is not open for 
debate under the terms of the Human Research rule. And more 
importantly, such a question does not provide a basis for a hearing (40 
CFR 178.32(b)(1)).
    Second, Petitioners argue that insufficient weight was given the 
prior independent reports on the Arnold study. However, the weight EPA 
should give under the Human Research rule to pre-rule independent 
reviews as opposed to the conclusions of the HSRB--the body established 
by the rule for the purpose of aiding EPA's implementation of it--is a 
legal/policy question and not a factual one. Hearings will not be 
granted on legal/policy issues (40 CFR 178.32(b)(1)).
    Finally, Petitioners' claims that EPA and the HSRB identified 
merely ``technical'' deficiencies in the Arnold study and that these 
deficiencies are ``address[ed]'' by ``data within the study itself'' 
and, therefore, do not render the study ``unreliable'' are no more than 
mere allegations and thus provide an insufficient basis for the 
granting of a hearing (40 CFR 178.32(b)(2)). Petitioners have proffered 
no evidence regarding the ``technical'' nature of the deficiencies in 
the Arnold study or how the deficiencies in sample size or variability 
are addressed within the study. Moreover, the record is clear that the 
deficiencies in the study are fundamental in nature and a hearing will 
not be granted on bald objections that are contradicted by the record 
(73 FR 42696 (July 23, 2008) (hearing denied when objection was 
contradicted by record and no evidence proffered in support)).
    3. Denial of objection. Petitioners have offered no response to 
EPA's explanation for accepting the HSRB's reasoning as to the 
weaknesses of the studies that rendered them scientifically invalid. 
Specifically, Petitioners do not address the HSRB's conclusion, adopted 
by EPA, that ``the weaknesses in the conduct and outcomes of the 
carbofuran human studies cast doubt on the utility of the data for * * 
* comparing across species in consideration of the interspecies 
uncertainty factor.'' Nor do Petitioners offer any reason as to why the 
HSRB's conclusion is not ``justifiable'' in light of the individual 
peer review reports from Drs. Brimijoin, Chambers, and Pope. Actually, 
there are several very good reasons for EPA to place primary weight on 
the HSRB's report compared to the three individual reports from Drs. 
Brimijoin, Chambers, and Pope prepared in 1997. First, the prior 
reports were not produced under the rubric of the Human Research rule, 
which has a different scope of inquiry than a traditional peer review. 
Second, Drs. Brimijoin, Chambers, and Pope made their recommendation 
regarding use of the Arnold study for a RfD in the context of a very 
different overall database for carbofuran. A significant number of new 
toxicity studies have been submitted since 1997. Third, Drs. Brimijoin, 
Chambers, and Pope all noted the severe deficiencies in the Arnold 
study but proposed that they be dealt with through the use of 
additional safety factors. Given these considerations it was reasonable 
for EPA to place primary reliance on the HSRB's report.
    The bulk of Petitioners' argument concerning EPA's determination on 
the scientific validity of the Arnold study is devoted to suggesting 
that the HSRB's review of the Arnold study was somehow ``inadequate'' 
because two members of the HSRB (Drs. Brimijoin and Chambers) were 
recused from the review due to their prior participation in a prior 
independent peer review. Petitioners also assert that the HSRB was 
hampered because EPA ``never informed the HSRB that it could call upon 
these experts for questioning or information regarding their prior peer 
review of the human studies, nor was it informed of--or provided with--
those prior reviews.''
    These claims are wholly without merit. As laid out in a letter 
responding to FMC's complaint regarding the recusal of Drs. Brimijoin 
and Chambers from the HSRB review of the carbofuran human studies, the 
recusal was entirely appropriate, and consistent with EPA's policies 
and regulations. The facts outlined in that letter also demonstrate 
that the HSRB's review was in no way restricted or hampered by the 
limited recusal of the two Board members.
    First, the HSRB was fully apprised of the earlier peer review 
reports. EPA relied on the reports because EPA's position before the 
HSRB was that the Arnold study should be found to meet the standard of 
the Human Research rule and would be useful in establishing points of 
departure for the carbofuran's single chemical assessment and in 
informing the interspecies uncertainty factor for the NMC CRA. It was 
clearly in EPA's interest that the HSRB be made aware of the earlier 
reports. In fact, the background materials provided to the Board 
included the peer review reports by Drs. Brimijoin, Chambers, and Pope, 
and the Agency's Weight-of-the-Evidence presentation to the HSRB which 
noted the contributions of these reviewers. Further, both the peer 
review reports and EPA's Weight-of-Evidence presentations were included 
in the public docket for the HSRB review. To the extent that the HSRB 
was still somehow unaware of the prior reports, FMC clearly referenced 
them in both its written and oral comments to the Board.
    Second, EPA's determination on the recusal of Drs. Brimijoin and 
Chambers was clearly consistent with Agency policy and well with EPA's 
discretion. The EPA's Peer Review Handbook (3rd Edition) (Ref. 80) 
provides guidance about peer review processes of the Agency. Of 
particular relevance is the Handbook's guidance regarding independent 
peer reviewers. While the Handbook notes that there is no prohibition 
against using the same peer reviewer more than once on the same 
product, it nevertheless advises that ``it is preferable to use 
different people each time to provide a broader perspective (Ref. 80 at 
13). Further the Handbook advises that the review of experts who ``have 
participated substantially in the development of a product * * * may 
not qualify as unbiased, independent peer review * * *'' (Id.). 
Therefore, EPA concluded that, under the circumstances, a question 
could be raised regarding the impartiality of Drs. Brimijoin and 
Chambers from the particular matter under review by the HSRB. Further 
support on this point can be found in the regulations at 5 CFR 
2635.502(a)(2), and in the preamble to the original regulation (56 FR 
33778 (July 23, 1991)).
    In light of these considerations, EPA addressed the appearance 
issue regarding Drs. Brimijoin and Chambers by determining whether 
authorization by the Agency designee should be invoked (see, 5 CFR 
2635.502(d)). Three factors were particularly relevant to the 
determination of Drs. Brimijoin and Chambers (see, 5 CFR 
2635.502(d)(4), (5), and (6)): the sensitivity of the

[[Page 59675]]

matter, the difficulty of reassigning the matter to another employee, 
and adjustments that may be made in the employee's duties that would 
reduce or eliminate the likelihood that a reasonable person would 
question the employee's impartiality. After considering these factors, 
the Agency decided the prudent course was be to recuse Drs. Brimijoin 
and Chambers from the HSRB carbofuran discussion but to authorize 
limited, as needed, participation.
    As documented in Dr. William Farland's May 1, 2006 memorandum 
entitled, ``Ethics Determination for Participation at the May 2-3, 2006 
EPA Human Studies Review Board Meeting'' (Ref. 39), EPA authorized the 
HSRB to ask Drs. Brimijoin and Chambers clarifying questions regarding 
their 1997 review, in the event that the HSRB deemed it necessary as 
part of their deliberations. At no point during the meeting did any of 
the HSRB's members indicate in any way that they wanted to consult with 
their recused colleagues. Nor did any of the members state that they 
wanted clarification on any point associated with the study.
    For all of the above reasons, Petitioners' objection on this point 
is denied.

I. Objections to Revocation of Import Tolerances

    Petitioners object to EPA's revocation of the tolerances for 
imported foods along with the tolerances associated with domestic uses. 
Petitioners allege that the revocation of the import tolerances is not 
supported by the available data because EPA's own risk assessments 
conclude that, when considered separately from the domestic uses, the 
residues from imported foods covered by these tolerances are ``safe.'' 
Petitioners further argue that EPA ``has not asserted any claim or 
rationale in the Final Order justifying its conclusions that the import 
tolerances are unsafe'' and therefore the revocation is unjustified.
    1. Background. In the proposed rule, EPA explained that its finding 
that aggregate exposure from all of the existing uses of carbofuran is 
not safe does not necessarily mean that no individual tolerance or 
group of tolerances could meet the FFDCA 408(b)(2) safety standard and 
be maintained (73 FR 44865 (July 31, 2008)). Rather, to the extent 
parties wanted to retain a particular subset of existing tolerances, 
the onus was on commenters to identify those uses and to submit 
information to demonstrate that the tolerance(s) meet the statutory 
standard. Indeed, EPA specifically identified the import tolerances as 
a subset that might meet the safety standard (Id.).
    No one submitted any comments alleging the need to retain 
individual tolerances for purposes of imports, or indicated an 
intention to seek to maintain those tolerances. The only subset of 
tolerances that commenters suggested was safe was the subset identified 
by the Petitioners, which included the import tolerances along with 
four domestic food uses.
    In the final rule, EPA analyzed the aggregate exposures from the 
subset of tolerances the Petitioners sought to retain, and concluded 
that the aggregate residues from food covered by those tolerances and 
from residues in drinking water are unsafe (74 FR 23084-23088).
    2. Denial of hearing request. A hearing is denied on this subissue 
because there is no disputed factual matter for resolution at a 
hearing. As the objection notes, EPA and Petitioners' risk assessment 
both concluded that the residues from imported food alone fell within 
the risk cup (Obj. at 52-54). The only issue this objection raises is 
whether EPA should have independently determined to retain a subset of 
the tolerances that Petitioners sought to maintain. This is a legal 
issue, and hearings are not appropriate on such issues (40 CFR 
178.32(b)(1)). (See 73 FR 42696-42697 (July 23, 2008) (denying NRDC's 
request for a hearing on objection that children's safety factor could 
not be reduced in absence of endocrine screening data). FDA also has 
repeatedly confirmed that the application of a legal standard to 
undisputed facts is a question of law for which a hearing is not 
required. (See, e.g., 68 FR 46403, 46406 n.18, 46408, 46409 (August 5, 
2003) (whether facts in the record show there is a reasonable certainty 
of no harm is a question of law; whether a particular effect is a 
``harm'' is a question of law)).
    In addition, Petitioners failed to raise this issue as part of 
their comments on the proposed rule, and never requested retention of 
only the import tolerances. Accordingly, as discussed in Unit VI.D, EPA 
considers this issue to have been untimely raised, and therefore 
waived. (See, 73 FR 42,696 (July 23, 2008) (denying NRDC's hearing 
request on claims not presented in their original petition); 72 FR 
39318, 39324 (July 18, 2007) (ruling that parties may not raise new 
issues in filing objections to EPA's denial of original petition)).
    3. Denial of Objection. Petitioners incorrectly allege that EPA 
provided no rationale for the revocations of the import tolerances. In 
the final rule, EPA clearly found that the aggregate exposures to 
carbofuran residues from all remaining uses, when combined with 
residues found in drinking water, were unsafe (74 FR 23084-23088 (May 
15, 2009).
    EPA can only maintain tolerances that it can determine will be 
``safe'' within the meaning of section 408(b)(2)(A)(ii). In making this 
determination, EPA must consider aggregate exposures from ``dietary 
exposure under the tolerance and all other tolerances in effect for the 
pesticide chemical residue, and exposure from other non-occupational 
sources'' (21 U.S.C. 346a(b)(2)(D)(vi)). At the time of the final rule, 
EPA evaluated the safety to the public from all dietary exposures to 
residues of carbofuran, which included not only the import tolerances, 
but also from residues on foods associated with domestic registrations 
and from residues in drinking water contaminated by the domestic uses. 
Indeed, until domestic use ceases--or at least until EPA has a 
reasonable basis to believe that it will cease--the Agency has no 
discretion to ignore the exposures from those uses. And revocation of 
the tolerances themselves does not necessarily resolve the issue, given 
the circumstances here. Until the registrations are cancelled, residues 
from contaminated drinking water, which is the primary contributor to 
the risks, must be included in EPA's risk assessment (Id).
    The consequence of this requirement is that, when one tolerance is 
unsafe, all tolerances are equally unsafe until aggregate exposures 
have been reduced to acceptable levels. Accordingly, in circumstances 
where aggregate exposures exceed the risk cup, there are potentially 
multiple variations of the potential subset of tolerances that might 
meet the safety standard. FFDCA section 408 does not compel EPA to 
determine the appropriate subset that would meet the safety standard. 
EPA is compelled ``to revoke or modify a tolerance if [EPA] determines 
it is not safe,'' but the statute grants EPA the discretion to 
determine how to proceed where more than one tolerance is unsafe. EPA's 
general policy in such situations is not to independently select the 
subset that meets the standard, but to rely on the pesticide registrant 
and the public to determine which of the various subsets of tolerances 
are of sufficient importance to warrant retention. There are a number 
of reasons EPA adopted this policy; it would be an unreasonable burden 
for the Agency to evaluate every possible combination of tolerances 
that might fit within the risk cup. In addition, if there were multiple 
different combinations that might within the risk cup, it is not clear 
that any party would

[[Page 59676]]

agree that EPA had selected the appropriate combination of tolerances. 
This is particularly relevant, since EPA relies on individual entities 
to maintain the tolerance, by continuing to submit necessary data to 
demonstrate the continuing safety of the covered residues.

J. Summary of Reasons for Denial of Petitioners' Objections and Hearing 
Requests

    1. General Denial. All of Petitioners' objections and hearing 
requests are denied because they are irrelevant, and thus immaterial, 
to EPA's final regulation revoking carbofuran tolerances. The lack of 
relevance stems from Petitioners' decision to object not to the safety 
decision EPA made in its final revocation regulation but to instead 
argue that EPA should reach a different decision based on FMC's 
proposed changes to the carbofuran registration that were submitted to 
EPA 44 days after the regulation published in the Federal Register. 
These proposed registration changes are central to and inextricably 
intertwined with the contention that underlies all of Petitioners' 
objections--that the carbofuran tolerances are safe, because in order 
to retain the contested tolerances, Petitioners must succeed on all of 
their objections. There exist statutory and regulatory procedures under 
FIFRA for FMC to pursue an amended carbofuran registration. As part of 
seeking an amended registration, FMC may petition to reestablish the 
revoked carbofuran tolerances. However, it is not proper to object to a 
final FFDCA tolerance revocation regulation based on the assertion that 
subsequently-filed, and as of yet unapproved FIFRA registration 
amendments, may change the risk picture under the FFDCA.
    FMC has had ample opportunity prior to issuance of the final 
tolerance revocation regulation to amend its FIFRA registration, 
whether during the comment period on the proposed rule, the extended 
reregistration process, or the public process initiated as part of the 
NOIC for carbofuran. And FMC has requested a number of modifications to 
its registrations during that time period. Yet, FMC has waited until 
EPA issued a final revocation regulation finding that carbofuran 
tolerances are unsafe, particularly as to infants and children, before 
filing its latest series of proposed FIFRA registration amendments. For 
this FFDCA proceeding, that is too late. The FFDCA commands that EPA 
``shall modify or revoke a tolerance if the Administrator determines it 
is not safe'' (21 U.S.C. 346a(b)(2)(A)(i)). The statute also places EPA 
under a special injunction to protect infants and children from the 
risks of pesticides (21 U.S.C. 346a(b)(2)(C)). EPA has made a final 
determination that carbofuran tolerances are unsafe and further 
determined that that lack of safety falls hardest on infants and 
children. Petitioners had the statutory right under FFDCA to challenge 
the accuracy of EPA's safety finding on carbofuran tolerances. FMC also 
has the statutory right under FIFRA to request amendment of its 
registration. What Petitioners may not do is prolong the FFDCA 
tolerance revocation process by challenging EPA's safety determination 
based on proposed FIFRA registration changes that were not before EPA 
at the time of its final revocation decision.
    2. Alternate Grounds for Denial. Despite the fact that Petitioners' 
objections and hearing requests are facially defective for reliance on 
newly-proposed FIFRA registration amendments, EPA has carefully 
examined each of Petitioners' objections and hearing requests and found 
that, in every instance, there are alternate grounds for denial. Those 
grounds are summarized below.
    There are multiple problems with Petitioners' hearing requests. 
Many of these problems stem from the Petitioners' decision to withhold 
analyses and information from the notice-and-comment rulemaking portion 
of this proceeding. Thus, despite EPA's clear warning that issues not 
raised in comments on the proposed rule, and information not submitted 
in that same timeframe, would be considered waived, Petitioners 
included several new issues, and numerous documents and analyses for 
the first time with their objections although they were clearly 
available earlier. Petitioners also have, for the most part, ignored 
how EPA responded to the comments they did submit in the notice-and-
comment rulemaking, and instead have often merely recycled their 
earlier comments as objections without addressing the reasons why EPA 
found them lacking in the first instance. This strategy, unfortunately 
for Petitioners, is fatal to many of their hearing requests and 
objections. EPA will not grant hearings on issues that have been 
waived, on issues where supporting documents were untimely submitted, 
or on claims that have become stale in that EPA addressed them in the 
final rule and Petitioners have not responded by clarifying where 
disputed issues still remain.
    It is not as if Petitioners lacked warning that EPA would take such 
an approach. Not only did EPA clearly state in the proposed rule that 
comments and information must be submitted in the comment period to be 
preserved but in 2007 EPA denied a hearing to a party who treated the 
notice-and-comment rulemaking process in a similarly cavalier fashion. 
In that instance, the party in question, like Petitioners, filed 
objections that largely mirrored its earlier submissions to the Agency 
without taking into account how EPA's final action had altered the 
nature of issues in dispute (See, e.g., 73 FR 42693 (``NRDC's 
objections largely restate the claims in its petition. Significantly, 
NRDC does not acknowledge or respond to the DDVP dietary and 
residential risk assessments made in response to the NRDC 
petition.'')). Such objections and hearing requests were denied for a 
lack of materiality (73 FR 42698-42699 (``When an objector does not 
challenge EPA conclusions in the section 408(d)(4)(iii) order but 
rather challenges some prior conclusion that was superseded by the 
section 408(d)(4)(iii) order, the objector has not raised a live 
controversy as to an issue material to the section 408(d)(4)(iii) 
order.'').
    a. Children's Safety Factor Objection. In support of their 
objection on the children's safety factor, Petitioners put forward 
several arguments; EPA summarizes below the various reasons for 
rejecting Petitioners' hearing requests and objections on each 
argument. Given the voluminous number of arguments asserted by 
petitioners in support of this objection, it is easy to lose track of 
the fact that all of the arguments relate to a single decision by EPA--
the decision to reduce the presumptive 10X children's safety factor to 
4X, rather than to 1X or 2X as the Petitioners desire.
    (i) Subissue: Are brain AChE measures in juveniles adequately 
protective of CNS effects in juveniles? EPA based its determination to 
reduce the children's safety factor to 4X on the ratio of sensitivity 
shown between carbofuran's effects on RBC AChE and brain AChE in 
juvenile rats. It is EPA's general policy to rely on RBC AChE as a 
surrogate for effects on the PNS but Petitioners failed to provide 
adequate RBC AChE data in juveniles to fully characterize the dose 
level of concern for PNS effects in infants and children. Petitioners 
claim EPA was wrong from the start. They claim that once EPA determined 
it had adequate data on brain AChE, the RBC data was irrelevant because 
brain AChE is an adequately-protective surrogate for PNS effects.
    Petitioners' hearing requests and objections on this issue are 
denied for identical reasons: the available evidence

[[Page 59677]]

identified by petitioners is ``insufficient to justify the factual 
determination urged'' (40 CFR 178.32(b)(2)). The critical issue with 
regard to EPA's children's safety factor decision is whether EPA has 
reliable data to ensure that residues of carbofuran in food will not 
cause adverse effects on infants and children's PNS. Petitioners claim 
that carbofuran data on brain AChE in juveniles is such reliable data. 
However, the evidence they proffer to support such an assertion is 
facially insufficient. Primarily, Petitioners cite data involving 
comparisons of brain AChE and PNS effects in adult animals. But 
evidence from adult animals is beside the point; the question is 
whether brain AChE in juveniles is protective of the PNS in juveniles. 
For at least 25 years, EPA has required toxicity tests be performed 
with pre- and post-natal animals as well as adult animals because young 
animals can be more sensitive and affected in a different manner than 
adults. Further, the only studies Petitioners cite that compared brain 
AChE in juveniles with PNS effects in juveniles, were conducted using 
other pesticides. For good reason, EPA requires that pesticides be 
individually tested in toxicity studies. Moreover, the majority of the 
data cited by Petitioners in other chemicals actually fails to 
demonstrate that the brain is more sensitive than the PNS, and the 
remainder of the evidence is, at best, merely equivocal on this point.
    To reiterate, if EPA chooses to select a children's safety factor 
different than 10X, it bears the statutory burden of showing that 
reliable data support its determination that the selected factor is 
safe for infants and children. Thus, Petitioners, in seeking to 
establish that EPA erred by not selecting an even lower children's 
safety factor for carbofuran (in fact, no such factor at all), 
similarly bear the burden of showing that there are reliable data for 
the proposition that juvenile brain AChE data for carbofuran are 
protective of PNS effects in children. Petitioners' equivocal and 
largely irrelevant proffer cannot meet that standard, particularly 
where EPA is lacking data it has traditionally-required on 
cholinesterase-inhibiting pesticides to protect against PNS effects, 
and the data EPA does have on measures of PNS effects indicate that 
effects on the juvenile PNS occur at lower doses than effects on brain 
AChE.
    (ii) Subissue: Are RBC AChE measures adequately reliable evidence 
of CNS effects? As a corollary to their claim that brain AChE measures 
are adequately protective of PNS effects, Petitioners also argue that 
RBC is not an appropriate surrogate for CNS effects in most 
circumstances. A hearing is not warranted on this subissue because 
Petitioners' evidentiary proffers either concern matters of undisputed 
fact (e.g., RBC AChE inhibition is not an adverse effect, RBC AChE can 
be variable at low doses) or inadequate and irrelevant data on other 
pesticides. Further, Petitioners' claim basically reduces to an 
argument over which is the ``preferred'' surrogate for PNS effects in 
the absence of data directly measuring such effects. Thus, this 
subissue is an argument about science policy and EPA's regulations are 
clear that hearings will not be held on policy matters. Even more 
problematic to Petitioners' hearing request on this subissue is its 
lack of materiality. Having failed in the previous subissue to proffer 
sufficient evidence to show carbofuran brain AChE data in juveniles is 
protective of carbofuran's effect on the PNS in juveniles, Petitioners' 
attempt to attack EPA's basis for addressing carbofuran's effects on 
the PNS in juveniles can only undercut Petitioners' ability to 
demonstrate the safety of the carbofuran tolerances. With the demise of 
Petitioners' brain AChE argument, EPA's analysis of the RBC AChE data 
is the only remaining basis for reducing the children's safety factor. 
If Petitioners are successful in showing that RBC AChE data are not a 
reliable measure of PNS effects in juveniles, EPA would have no 
reliable data on such impacts and would be required to retain the full 
children's safety factor. As such, Petitioners' claim is immaterial; 
even if the claim were upheld, it would not justify the ultimate relief 
sought by Petitioners.
    As to Petitioners' objection to EPA's science policy decision to 
use RBC cholinesterase as a surrogate for PNS effects, EPA explains in 
detail in Unit VI.E, the biological basis for its policy decision, the 
multitude of data supporting its approach, and the frequent 
consultations with the SAP concerning the wisdom of using such an 
approach. The equivocal data submitted by Petitioners does not raise a 
serious question regarding EPA's policy. In any event, as noted with 
regard to the hearing request, this subissue lacks materiality in that 
success on this subissue by Petitioners would retard rather than 
advance their challenge to EPA's action.
    (iii) Subissue: Is ``lip-smacking'' a CNS or PNS effect? 
Petitioners object that EPA's evidence of ``lip smacking'' in a 
carbofuran adult developmental rat study does not support concern for 
potential PNS effects because lip smacking is more properly correlated 
to CNS, rather than PNS inhibition. A hearing is denied on this issue 
because Petitioners did not raise this issue in its comments on the 
proposed tolerance revocation. A hearing on this issue is also 
inappropriate because the issue is immaterial. EPA's decision that a 4X 
children's safety factor is appropriate did not rest exclusively--or 
even significantly--on the effects observed in this developmental 
study. Rather, EPA retained the children's safety factor based on the 
lack of data in the PNS and/or a surrogate at the low end of the 
response curve, and the fact that the available pup RBC data at higher 
doses affirmatively indicate that the PNS appears to be significantly 
more sensitive than the CNS.
    Petitioners' objection on this subissue is denied because both 
parties agree that muscle fasiculations, which are the movements EPA 
described at the SAP meeting and in the proposed and final rules, are 
PNS-mediated effects. Further, it is unclear that the effects described 
in the studies Petitioners submitted are actually the same effects seen 
in the carbofuran study; other factors in the studies suggest that the 
movements being studied are not purely cholinergic, which calls into 
question whether the effects are the same. For the same reason, this 
calls into question the contention that the effects are exclusively 
CNS-related. Finally, the cited studies fail to support Petitioners' 
remaining contentions. Since it is unclear that the studies actually 
describe the same effects, and Petitioners have failed to demonstrate 
that the effects are exclusively CNS-related, the evidence does not, 
therefore, rebut EPA's conclusions regarding the movements described in 
the carbofuran study.
    (iv) Subissue: Did EPA err by relying on studies not conducted 
pursuant to EPA's GLP regulations? Petitioners claim that EPA's 
reliance on the ORD data is problematic because the data were not 
conducted in accordance with EPA's GLP regulations at 40 CFR part 160. 
Petitioners have not cited any evidence suggesting there is a 
substantive problem with the ORD data or made any arguments to such 
effect. Thus, this subissue presents only a legal question and legal 
questions are not appropriate grounds for a hearing. EPA denies 
Petitioners' objection on this point because EPA regulations make clear 
its GLP regulations only apply to studies in support of a pesticide 
registration or tolerance (40 CFR 160.1(a), 160.3). In any event, non-
compliance with the GLP regulations does not automatically disqualify a 
study from EPA consideration but rather goes to reliability (40 CFR 
160.17(a)).

[[Page 59678]]

(As noted, Petitioners have made no claim that the ORD data is not 
reliable.).
    (v) Subissue: Was EPA's selection of a 4X children's safety factor 
consistent with EPA's approach to other carbamate pesticides? 
Petitioners object that EPA was inconsistent in retaining a 4X 
children's safety factor for carbofuran given that EPA removed the 
children's safety factor for other carbamates. A hearing is not 
appropriate on this subissue because it presents a purely legal 
question. There is no dispute regarding the facts of EPA's decision in 
each case, the only question is whether EPA acted appropriately on 
carbofuran given its decision on the children's safety factor for other 
carbamate pesticides, such as carbaryl. The objection is denied because 
EPA's decisions in each case were consistent; EPA applied a different 
children's safety factor to carbofuran than to the other carbamate 
pesticides based on the different facts in each case. For example, the 
data showed that carbaryl differed significantly from carbofuran in 
terms of each chemical's relative sensitivity in juveniles with regard 
to brain and RBC AChE inhibition. For carbofuran, EPA concluded that 
RBC AChE inhibition in juveniles was more sensitive than brain AChE 
inhibition in juveniles by a factor of 4X. For carbaryl, the AChE 
inhibition in brain and RBC of juveniles was essentially equal.
    (vi) Subissue: Did EPA err in not using within-animal brain to RBC 
AChE inhibition comparisons to derive the children's safety factor? EPA 
derived an alternate to the default 10X children's safety factor based 
on the ratio of RBC and brain AChE inhibition. In their comments on the 
proposed rule, Petitioners criticized this approach, arguing that EPA 
should have compared the RBC and brain AChE inhibition levels at the 
same time in the same rat when these rats are exposed to carbofuran. 
Petitioners claimed to have done such an analysis and that the analysis 
showed that within rat inhibition levels in brain and RBC AChE were 
roughly equivalent. Although the results of the statistical analyses 
were summarized in the comments, the underlying analysis was not 
submitted. In the final tolerance revocation regulation, EPA 
extensively reviewed the ``within animal'' approach and rejected it as 
fundamentally flawed in several regards. Additionally, EPA noted that 
EPA's review of the Petitioners' suggested approach showed that it 
produced results, which are in fact consistent with EPA's conclusions. 
In their objections, Petitioners do not respond to EPA's rejection of 
the within animal approach in the final tolerance revocation rule 
either by explaining their disagreement with EPA's critique or 
proffering evidence to counter EPA's conclusion. Rather, Petitioners 
simply resubmitted essentially the same comments they provided on the 
proposed rule. Petitioners also again failed to submit the underlying 
analysis supporting their within animal calculations.
    A hearing on this subissue is not appropriate for two reasons. 
First, Petitioners' repeated failure to submit the analysis supporting 
their claim reduces this objection to a mere allegation. Under EPA's 
regulations, hearings will not be granted on the basis of mere 
allegations. More importantly, Petitioners' objection on this subissue 
is irrelevant, and therefore immaterial, with regard to EPA's final 
tolerance revocation regulation because Petitioners ignored EPA's 
extensive analysis of this subissue in the final rule and refiled their 
comments on the proposal as if EPA's determination in the final rule 
did not exist. The statute, however, requires that objections be filed 
on the final rule, not on the proposal. By ignoring the EPA's final 
rule on this subissue, Petitioners have failed to lodge a relevant 
objection. Both EPA and FDA precedent make clear that when the agency 
substantively responds to comments on the proposal, the commenter may 
only keep that issue alive in its objections by addressing the agency's 
substantive response. In other words, the final rule is the focal point 
for determining whether issues remain that must be resolved by the 
objection and hearing process. Any other approach relegates the notice-
and-comment rulemaking stage of the revocation process to a meaningless 
exercise.
    Petitioners' objections on this subissue are denied as irrelevant 
to the conclusions reached in the final rule. The final rule explains 
why Petitioners' arguments are without a basis, and Petitioners have 
failed to address that explanation. For essentially the same reasons, 
EPA denies the objection.
    For essentially the same reasons, EPA denies the hearing request 
and objection designated above as Objection/hearing request sub issue: 
Technical Flaws in EPA's statistical comparisons. Petitioners' 
objection and hearing request on this subissue consist of mere 
reiteration of the comments submitted in response to the proposed 
tolerance revocation. The final rule explained the reasons that 
Petitioners' arguments are flawed, and the objections are denied for 
the same reasons.
    (vii) Subissue: Is EPA's approach to comparing brain and RBC AChE 
inhibition in juveniles due to carbofuran exposure scientifically 
valid? Petitioners allege that EPA's approach to calculating the 
relative sensitivity between AChE inhibition in brain and RBC in 
juveniles is not scientifically valid. EPA derived the ratio of RBC and 
brain AChE inhibition using the data on administered dose (measured in 
terms of BMD50) for PND11 animals. In addition, the 
Petitioners criticize EPA for incorrectly assuming that the 
relationship of the dose response curve between BMD50s and 
BMD10s is linear, which they claim overstates the potential 
differences. In support of the claim that EPA's approach overstates the 
differences, Petitioners argue that data suggests that 
BMD50s for brain and RBC AChE inhibition for the carbamates 
tend to diverge more than the dose levels that cause the low levels of 
AChE inhibition used to select the PoD (i.e., the BMD10s), 
which demonstrates that at levels causing lower levels of inhibition, 
no safety factor is necessary. Petitioners' argument is that the 4X 
ratio EPA calculated based on the BMD50 is unnecessarily 
protective, because the difference between brain and RBC at the doses 
causing lower levels of inhibition (i.e., 10%), which are the levels at 
which EPA is regulating, would not be significant.
    Petitioners' hearing request on this subissue is denied for two 
reasons. First, Petitioners proffered no evidence on any carbamate, 
much less carbofuran, in support of their claim that BMD50s 
for the carbamates tend to diverge more than the BMD10s or 
that the response curve between BMD50s and BMD10s 
is not linear. A hearing will not be granted on the basis of mere 
allegations. Second, Petitioners' claims are immaterial because unless 
Petitioners can show what the relationship is between the response 
curves for BMD50s and BMD10s (an assertion they 
have not even made), a showing that EPA's assumption of linearity is 
incorrect can only force EPA to abandon the 4X children's safety factor 
in favor of the default 10X value.
    The objection that EPA's modeling is scientifically invalid is 
denied. EPA's modeling has been repeatedly reviewed and approved by the 
SAP, including most recently with respect to the modeling of 
carbofuran's dose-response curves. There is no indication in the 
modeling that EPA's assumption of parallel dose-response curves 
overstates the difference, and given the absence of data supplied by 
Petitioners in support of this objection, the objection is denied.
    (viii) Subissue: Did EPA err by combining data from different 
toxicological studies in calculating the estimates of BMD50s 
that serves as

[[Page 59679]]

quantitative support for derivation of the 4X childrens' safety factor? 
In its risk assessment, EPA relied on all of the valid data from the 
available studies to calculate the estimates that served as the PoD, 
and to calculate BMD50s used in choosing the children's 
safety factor. In their comments on the proposed rule, Petitioners 
claimed that EPA's decision to combine data for different strains of 
rats, sexes, experiments, laboratories, dates, dose preparations, rat 
ages, and times between dosing and AChE measurement, is problematic, 
claiming that these differences in study design severely limit the 
validity of EPA's comparisons and caused EPA to overestimate the 
difference between brain and RBC AChE inhibition. EPA responded to 
these comments in full during the rulemaking (74 FR 23052-23053; Ref. 
85). Petitioners referenced their earlier comments in their objections, 
but presented no further evidence on any of these points. Nor in their 
objections and request for hearing did Petitioners address EPA's 
explanation set forth in the final rule.
    A hearing is not appropriate on this subissue because Petitioners 
have not challenged the basis EPA asserted in the final rule for 
rejecting their concerns nor have they proffered any evidence that 
calls the substance of EPA's conclusions into question. A hearing is 
not warranted on the basis of mere denials or contentions, nor when the 
commenter simply reiterates comments raised in response to the proposed 
rule (40 CFR 178.32(b)(1) and (2)). Additionally, this hearing request 
is rejected for lack of materiality. If EPA abandoned its sophisticated 
analysis of multiple studies and datasets and simply followed the 
general approach laid out in its BMD policy, EPA would have chosen a 
significantly lower BMD dramatically raising EPA's risk estimates.
    Petitioners' objection on this subissue is denied because 
Petitioners have not responded to the explanation EPA provided in the 
final rule supporting its meta-analysis of multiple studies. Consistent 
with Agency guidance, EPA believes that consideration of all available 
data is the scientifically more defensible approach, rather than the 
selective exclusion of reliable data. Petitioners' objection on this 
point is particularly weak given that their analysis also combines 
various data sets and only arrives at a higher estimate of the BMD by 
selectively excluding, without explanation, the data most pertinent to 
assessing carbofuran's acute affects.
    b. Drinking Water Exposure Objection--In large part, Petitioners' 
objections to EPA's assessment of carbofuran levels in drinking water 
are inextricably intertwined with their recently-proposed registration 
amendments which attempt to create a scheme whereby carbofuran use 
would be limited in individual watersheds. As explained above (see Unit 
VI.F.2.a), objections based on these recently-proposed registration 
amendments are irrelevant to EPA's determination in the final tolerance 
revocation rule. Nonetheless, in Unit VI.F, EPA exhaustively evaluated 
all of the arguments put forward in Petitioners' drinking water 
objection and explained why a hearing was not appropriate on any of 
these arguments and why, on the merits, the arguments were without 
basis. Below EPA has summarized its reasoning.
    The first four subissues below pertain to EPA's assessment of the 
carbofuran groundwater exposure assessment and the last eight address 
the surface water assessment. In this regard, it is important to note 
that, in order to determine that a tolerance for a particular use will 
be safe, EPA must be able to determine that anticipated concentrations 
in both surface water and ground water resulting from that use will be 
safe.
    (i) Subissue: Did EPA err in relying on the results of the 
prospective ground water study (PGW) and historical monitoring to 
validate groundwater exposure estimate? The Petitioners object that EPA 
should not have relied for validation on their PGW study or historical 
monitoring data. They argue that these data no longer reflect current 
use patterns and that all areas like those seen in the PGW have now 
been removed from the carbofuran label.
    A hearing is not appropriate on this subissue because the 
Petitioners have failed to proffer evidence, which would, if 
established, resolve a material issue in their favor. First, 
Petitioners fail to take into account the clear record evidence that 
EPA scaled the PGW modeling to reflect the lower current use rates. 
Second, Petitioners are simply incorrect to claim that EPA 
``validated'' its quantitative groundwater assessment based on historic 
monitoring data that are not reflective of current application rates. 
The targeted monitoring data used for validation were based on 
application rates that are identical or lower than the current use 
rates. Third, the majority of Petitioners' evidence is untimely, and to 
the extent Petitioners' are claiming that the PGW and other targeted 
monitoring data are not reflective of FMC's June 29, 2009 proposed 
registration amendments, that claim is irrelevant to the current 
proceeding. Finally, Petitioners' evidentiary proffer on the PGW is 
internally contradictory given that Petitioners' own experts relied on 
the PGW to validate the modeling submitted in support of this 
objection.
    The objection on this subissue is denied because timely evidence 
and reasoning submitted by Petitioners is contradictory, non-probative, 
or flatly contradicted by the record.
    (ii) Subissue: Does EPA's assessment of carbofuran levels in ground 
water account for all of FMC's label mitigation measures and ``rely on 
unrealistic and overly conservative assumptions about potential 
concentrations''? In this objection, the Petitioners allege that 
maximum concentrations of carbofuran in groundwater are expected to be 
below 1.1 ppb, based on their proposed geographic restrictions and well 
setbacks. EPA believes Petitioners' objection and hearing request on 
this subissue is inextricably intertwined with FMC's recently-submitted 
FIFRA registration amendments and thus the objection is denied as 
irrelevant on that account.
    Nonetheless, to the extent possible EPA has attempted to evaluate 
this objection based on the label mitigation measures submitted and 
adopted prior to issuance of the final tolerance revocation rule and 
ruled on it on that basis. EPA denies the objection and its associated 
hearing request because Petitioners have again failed to object to 
EPA's final rule. It is clear from the record that EPA's final rule and 
risk assessment did account for all of the risk mitigation measures 
submitted as part of the September 2008 comments. Petitioners have not 
raised any substantive challenge to the manner in which EPA's modeling 
addressed those measures. In addition, Petitioners' objections provide 
no further clarification as to what is meant by their claim that EPA's 
assessment relied on ``unrealistic and overly conservative 
assumptions.'' Therefore, this objection, and the attendant hearing 
request, is denied based on Petitioners' failure to state with 
``particularity * * * the basis for the objection * * *.''(40 CFR 
178.25(a)(2)). As Petitioners raised similar allegations in their 
comments, EPA has assumed that they intended to incorporate all of the 
issues raised in the comments on the proposed rule. However, EPA 
addressed these assertions in the final rule. Because Petitioners have 
once again ignored the explanations provided in the final rule, this 
objection and hearing request are denied as immaterial.
    (iii) Subissue: Is EPA's assessment of the levels of carbofuran in 
groundwater appropriate given the manner in which

[[Page 59680]]

EPA assessed groundwater exposures in the NMC CRA? Petitioners object 
that EPA's estimates in the final rule are inconsistent with the 
groundwater concentration estimates EPA developed for the NMC CRA. 
However, they do not identify any specific inconsistency, they simply 
make the general allegation. They allege that, by contrast, their 
assessment, which estimated maximum concentrations of 1.1 ppb, is 
consistent with the NMC CRA.
    EPA denies the request for a hearing on this sub-issue because 
there is no disputed factual matter for resolution (i.e., the manner in 
which EPA assessed groundwater exposure for carbofuran and for the NMCs 
is a matter of record); rather, the objection poses the legal question 
of whether it was appropriate for EPA to assess groundwater exposure 
for carbofuran and the NMCs in a different manner. Further, because 
Petitioners have not identified any specific inconsistency between the 
two groundwater exposure assessments, it constitutes nothing more than 
a mere allegation or denial. As EPA's regulations make clear, a mere 
``denial'' of an EPA position is not sufficient to satisfy the standard 
for granting a hearing (40 CFR 178.32(b)(2)). Finally, the claim that 
their modeling is consistent with the NMC CRA does not justify a 
hearing on this question. As EPA explained in the final rule, the 
values estimated in the modeling conducted for the NMC CRA are greater 
than the 1.1 ppb level that FMC claims is the maximum expected 1-in-10-
year peak concentration. A hearing is not warranted where the claim is 
clearly contradicted by the record (40 CFR 178.32(b)(2)).
    On the merits, Petitioners' objection is denied because the results 
of Petitioners' groundwater assessment are not consistent with the 
estimates developed for the NMC CRA. The NMC CRA examined carbofuran at 
two sites, northeast Florida and the Delmarva Peninsula. In Florida, 
concentrations were found to be below levels of concern because of high 
pH, but in Delmarva, both in corn and in melon scenarios EPA estimated 
that 90% of daily concentrations could be as high as 20.5 and 25.6 ppb, 
respectively. These values are far greater than the 1.1 ppb that 
Petitioners claim is the maximum expected 1-in-10-year peak 
concentration.
    (iv) Did EPA err in not using PCT data in assessing surface water 
exposure? The Petitioners object to the assumption in the surface water 
assessments in the final rule that 100% of the crops in a watershed 
will be treated with carbofuran. The Petitioners argue that actual 
carbofuran sales data on a county basis from 2002-present demonstrate 
that the current carbofuran PCT is less than 4.25%. Using this PCT, and 
taking into account the recently submitted ``no application buffers,'' 
the Petitioners allege that the modeling in Exhibit 15 demonstrates 
that carbofuran concentrations in surface water will not exceed 1.1 
ppb, ``which is below the level of concern.'' In support of this 
objection, the Petitioners reference county level sales data that were 
submitted to the Agency after the close of the comment period. They 
also reference the use tracking system proposed in their recent 
registration amendments (Exhibit 2) and the modeling contained in 
Exhibit 15. Because this subissue is inextricably intertwined with 
Petitioners' recently-proposed FIFRA registration amendments, it is 
denied as irrelevant.
    To the extent Petitioners' objection on this subissue is limited to 
EPA's refusal to use a 4% PCT in estimating drinking water 
concentrations in individual watersheds based on the information 
provided as part of their comments on the proposed rule, this objection 
and hearing request are also denied as immaterial. The Petitioners have 
failed to respond to EPA's explanation in the final rule that the 
information and methodology on which they relied to estimate a 4% PCT 
was fundamentally flawed, and to submit any evidence calling the basis 
of EPA's response into question (40 CFR 178.32(b)(3)). Additionally, 
the proffered evidence here is untimely. The sales data and methodology 
used to generate use estimates, as well as the modeling in Exhibit 15, 
were not submitted during the comment period on the proposed rule even 
though the information was clearly available to Petitioners (40 CFR 
178.32(b)(2)).
    Petitioners' objection on this subissue is denied because the 
proffered evidence is untimely and, even if considered, insufficient. 
Although EPA does use reliable data on pesticide usage in estimating 
exposure levels in food, this approach has limited applicability in 
drinking water assessments due to the differences in the sources of 
food and water for consumers. The food market in the United States is 
national in scope but the sources of drinking water are primarily 
local. Thus, while differences in the usage of pesticides across the 
country will average out in estimating pesticide exposure from food, 
such averaging is not applicable to estimating pesticide exposure in 
drinking water--i.e., a person's drinking water exposure is generally 
always from the same watershed. Moreover, the information that 
Petitioners submitted on PCT was not usage data--the type of 
information normally used in estimating PCT for food--but sales data. 
The link between sales data and the location of use is tenuous. Given 
that EPA lacks the information to allow EPA to generally use PCT 
information in estimating drinking water exposure, and the poor quality 
of information Petitioners submitted on usage (i.e. county-level sales 
data), EPA concludes it could not make an exposure estimate on 
carbofuran in drinking water with sufficient confidence to meet the 
FFDCA's reasonable certainty of no harm standard.
    (v) Subissue: Do the results of FMC surface water modeling 
establish that carbofuran levels will not exceed 1.1 ppb? The 
Petitioners claim that the prior surface water assessments submitted to 
the Agency and a new assessment incorporating FMC's newly-proposed 
FIFRA registration amendments demonstrate that carbofuran 
concentrations in surface water are not expected to exceed 1.1 ppb. 
Because this subissue is inextricably intertwined with Petitioners' 
recently-proposed FIFRA registration amendments, it is denied as 
irrelevant. Nonetheless, EPA has carefully evaluated all of 
Petitioners' allegation to determine if any of their claims meet the 
standard for a hearing or are otherwise meritorious.
    A hearing is also denied on this sub-issue because Petitioners' 
objection on this subissue is irrelevant, and therefore immaterial, 
with regard to EPA's final tolerance revocation regulation. Petitioners 
have not responded to EPA's extensive analysis of these studies, which 
included an explanation for the Agency's conclusion that they were 
significantly flawed, presented in the final rule. The statute, 
however, requires that objections be filed on the final rule not the 
proposal. By ignoring EPA's final rule on this subissue, Petitioners 
have failed to lodge a relevant objection. Both EPA and FDA precedent 
make clear that when the agency substantively responds to comments on 
the proposal, the commenter may only keep that issue alive in its 
objections by addressing the agency's substantive response (40 CFR 
178.32(b)(3)). Similarly, the Petitioners' new assessment directly 
relies on FMC's newly-proposed FIFRA registration amendments and is 
thus irrelevant to this proceeding. Their new assessment is also 
untimely in that it primarily appears to be a fuller description of 
Petitioners' National CWS Assessment, which was described, but not 
provided as part of their comments on the proposed rule (40 CFR 
178.32(b)(2)).

[[Page 59681]]

    EPA has outlined the substantial flaws in the previously-submitted 
assessments in the final tolerance revocation rule and in Unit VI.F, 
above. For the all the reasons cited therein, this objection is denied.
    (vi) Did EPA inappropriately rely on NAWQA monitoring data in 
assessing carbofuran levels in surface water? The Petitioners object to 
EPA's discussion in the final rule of the high concentrations detected 
in Zollner Creek in Oregon and claim that EPA inappropriately relied on 
NAWQA monitoring data in estimating surface water exposure levels of 
carbofuran. A hearing on this issue is denied because there are no 
material factual issues in dispute. The extent to which EPA discussed 
the Zollner Creek data as part of its discussion of monitoring results 
from all other NAWQA sites, SDWA post-treatment monitoring, and the 
results of field studies is clear on the record. The record is also 
clear regarding the degree of reliance EPA placed on monitoring data in 
estimating carbofuran levels in surface water. The objection on this 
subissue is denied because it was reasonable for EPA to consider NAWQA 
data in assessing the likelihood that carbofuran residues may be 
present in surface water. Moreover, the record is clear that, even 
though EPA considered the NAWQA data, it placed primary emphasis on the 
carbofuran levels detected in post-treatment SDWA monitoring.
    (vii) Should EPA consider FMC's newly-proposed terms of 
registration for carbofuran? The objection is denied because it is 
based on FMC's newly proposed revisions to its carbofuran registration 
that were submitted after publication of the final tolerance revocation 
rule and is thus irrelevant to this proceeding. An additional ground 
for denial of this objection and hearing request is that Petitioners 
proferred no evidence to support their allegation that these proposed 
requirements would be effective in limiting carbofuran exposure to the 
extent claimed
    (viii) Should EPA have used the NMC CRA surface water estimates in 
assessing exposure to carbofuran in surface water? Petitioners object 
to EPA's surface water exposure estimates on the ground that they are 
inconsistent with the estimates EPA developed for purposes of the NMC 
CRA. This hearing request is denied because there are no factual 
matters in dispute; rather, the only question is a legal one of whether 
it was inappropriate for EPA to use different approaches to assessing 
surface water exposure for the carbofuran surface water assessment and 
the cumulative assessment of surface water exposure for NMCs (40 CFR 
178.32(b)(1)). In addition, this issue was raised in Petitioners' 
comments on the proposed revocation. In the final revocation, EPA 
explained how the substantial differences between a cumulative risk 
assessment for a class of pesticides and a risk assessment for a single 
pesticide necessitate different approaches. Petitioners have not 
challenged the substance of EPA's response to their comments or 
submitted evidence that calls the substance of EPA's final rule 
conclusions into question, and the objection and associated hearing 
request is therefore immaterial (40 CFR 178.32(b)(3)). Finally, on 
multiple grounds, Petitioners' evidentiary proffer is insufficient to 
support a conclusion that there is a reasonable possibility that the 
issue could be resolved in their favor. Petitioners' objection on this 
subissue is denied for essentially the same reasons explained in the 
final tolerance revocation.
    (ix) Has EPA taken natural surface water pH conditions into 
account? The Petitioners contend that the PCT levels guaranteed by the 
recently proposed use tracking system, along with natural surface water 
pH conditions in the areas included under the revised label will ensure 
that potential exposures are de minimis. Because this objection is 
inextricably intertwined with FMC's newly-proposed FIFRA registration 
amendments, it is denied as irrelevant to this proceeding.
    Even assuming Petitioners' allegation concerning soil pH can be 
separated from the proposed registration amendments, Petitioners' 
claims are insufficient to justify the action urged (40 CFR 
178.32(b)(3)). Petitioners admit that their pH analyses explicitly only 
capture 95% of surface waters. Because EPA cannot ignore the other 5% 
of surface water, this information, even if established, would provide 
an insufficient basis on which EPA could reasonably conclude that the 
drinking water exposures would be ``safe.'' Additionally, the proffered 
evidence for this objection is untimely because although the effects of 
pH were clearly discussed in the proposed rule, Petitioners' claim and 
the analyses supporting it were not submitted during the comment 
period.
    For the same reasons, the Petitioners' objection is denied.
    (x) Has EPA taken the effect of existing drinking water treatment 
systems into account? The Petitioners contend that, in the areas where 
carbofuran use is allowed under revised labels, the majority of the 
total population is protected from carbofuran by water treatment 
systems and that the rest of the population is protected by 
Petitioners' newly-proposed FIFRA registration amendments. Because this 
objection is inextricably intertwined with FMC's newly-proposed FIFRA 
registration amendments, it is denied as irrelevant to this proceeding.
    Separating out the allegations that are independent from the new 
registration amendments, EPA denies this hearing request on the grounds 
that Petitioners' claims are insufficient to justify the action urged 
(40 CFR 178.32(b)(3)) in that they would fail to justify a conclusion 
that the carbofuran tolerances are safe. The fact that the majority of 
people are protected is irrelevant if major identifiable subpopulations 
are not. Further, both the objection and the proffered evidence are 
untimely because Petitioners' claims and analyses supporting them were 
not submitted during the comment period. For the same reasons, this 
objection is denied.
    c. Recovery Time Objection--(i) Subissue: Has EPA overstated risk 
through its approach to considering recovery time to the effects of 
carbofuran? For carbofuran, EPA estimated acute dietary exposure for 
the acute risk assessment by summing exposure over a 24-hour period. 
Because humans are likely to recover in a relatively short time period 
from any single carbofuran exposure, EPA also undertook a more 
sophisticated exposure assessment that took recovery time into effect. 
This more sophisticated analysis was not substituted for the 24-hour 
assessment approach but rather was used to evaluate whether the 24-hour 
approach substantially overstated risk. The reason for not simply 
adopting the assessment incorporating recovery time was based on 
concerns that other aspects of its exposure model tend to understate 
exposure. If the assessment using recovery time had suggested that 
carbofuran risks may be acceptable, EPA would have further examined how 
exposure should be assessed. However, because both the assessment based 
on 24-hour exposure and the one incorporating recovery time showed 
carbofuran exposures significantly exceed the safe level, EPA concluded 
that its exposure assessment was reasonable. Further supporting this 
conclusion was the fact that various other analyses showed that a 
single eating occasion could result in excessive risk to infants. 
Petitioners have objected to this approach claiming that recovery time 
should be included in EPA's ``primary'' risk assessment.
    EPA is denying this hearing request on two grounds. First, the 
objection fails

[[Page 59682]]

to present a disputed issue of material fact because EPA did 
incorporate recovery time into its analysis. Rather, Petitioners' only 
challenge is to whether EPA should have only presented risk estimates 
that accounted for recovery. This is a policy issue, and hearings are 
not appropriate on such (40 CFR 178.32(b)(1)).
    Second, the fact that EPA relied on 24-hour aggregate exposures in 
addition to analyses that accounted for recovery is not material, 
because even though accounting for recovery resulted in a 2-3X 
reduction in exposure estimates, many of EPA's estimates for aggregate 
exposures ranged between 2700% aPAD and 9400% aPAD for infants. 
Accounting for recovery does not, therefore, demonstrate that aggregate 
exposures will be safe for infants. Of greater significance in this 
regard is EPA's finding that infants are at risk from a single 
exposure. Recovery is only relevant, by definition, where the risk is 
derived from multiple exposures over time.
    Petitioners' objection to EPA's policy decision to present acute 
risks in terms of 24 hours of exposure is denied because EPA's policy 
approach here is reasonable. For the reasons explained in Unit VI.G, 
there are several factors that may cause EPA's exposure/risk model to 
either understate or overstate exposure/risk. It is unreasonable to 
present risks only incorporating factors that tend to reduce exposure/
risk estimates (e.g., recovery time), as Petitioners suggest. EPA's 
approach of evaluating the impact that these factors may have on the 
risk assessment is an appropriate method of taking all relevant factors 
into account.
    (ii) Subissue: Did EPA err in calculating carbofuran half-lives? In 
the proposed rule, EPA used half-lives of 150 minutes and 300 minutes, 
based on calculations derived for the NMC CRA. In the final rule, EPA 
calculated half-lives specific to carbofuran to ensure that its 
analyses accurately reflected carbofuran's risk. Petitioners contend 
that EPA's calculation of carbofuran half-lives of 186 minutes and 426 
minutes were flawed, and that the data instead support the use of a 
150-minute half-life.
    Petitioners' hearing requests on this subissue are denied for two 
reasons. First, Petitioners have not provided the underlying analyses 
conducted in support of their claims that the appropriate half-life for 
carbofuran is 150 minutes, rather than the 186 or 426 minutes that EPA 
calculated. Petitioners' evidentiary proffer thus consists of no more 
than mere allegations and denials. Hearings will not be granted on this 
basis (40 CFR 178.32(b)(2)).
    Further, the issue of the appropriate half-lives for carbofuran is 
not material. Petitioners have proffered no evidence to show that 
reliance on a 150-minute half-life rather than a 186-minute half-life 
would make a significant difference to their estimates. By contrast, in 
the risk assessment supporting the final rule, EPA's estimates show 
that the use of a 150-minute or 186-minute half-life makes little or no 
difference. In addition, EPA's final risk assessment found that infants 
are at risk from a single exposure. Recovery is only relevant, by 
definition, where the risk is derived from multiple exposures over 
time.
    EPA denies Petitioners' objection on this subissue because the 
evidence submitted fails to establish their allegations, or to rebut 
the data and analyses discussed in the final rule.
    d. Human Study Objection--Issue: Did EPA reasonably conclude that a 
human toxicity study with carbofuran was barred from EPA consideration 
by the Human Research Rule? In conducting its dietary risk assessment 
for carbofuran, EPA relied on toxicity data conducted with rats, and 
applied the default 10X interspecies factor to account for the 
potential uncertainty in extrapolating from animal data to humans. 
Petitioners object to the decision to use a 10X interspecies factor 
claiming that data from a human toxicity study (Arnold) provides a 
basis for reducing this factor to 3X. However, EPA has previously 
determined that the Arnold study lacks scientific validity and thus may 
not be considered by the Agency under EPA's Human Research rule. That 
decision was based on the advice of the HSRB, which found the Arnold 
study to constitute ``poor science'' (Ref. 38 at 11).
    Although Petitioners have made a number of arguments in support of 
adopting a 3X interspecies factor, all of the arguments rely on 
consideration of the Arnold study. Thus, as a preliminary matter, 
Petitioners must show that a hearing is appropriate based exclusively 
on whether EPA erred in determining that the Arnold study cannot be 
considered under the Human Research rule or, that even if a hearing is 
not warranted, that EPA's decision under the Human Research rule was 
incorrect.
    Petitioners have proffered no evidence that merits a hearing on 
EPA's application of the Human Research rule to the Arnold study. As an 
evidentiary proffer, Petitioners claim (1) that review of the Arnold 
study under the Human Research rule was too narrow in that it did not 
consider the Arnold study in light of the animal data; (2) that 
insufficient weight was given prior independent reports on the value of 
the Arnold study; (3) that the ``technical'' concerns raised by the 
HSRB are addressed by ``the data within the study'' and that these 
``technical'' deficiencies do not render the Arnold study unreliable. 
The first proffer is not material because the availability of animal 
data does not address the validity of the Arnold human study. At 
bottom, this issue involves a challenge to the policy underlying the 
Human Research rule that allows only limited consideration of human 
toxicity studies. A hearing is not appropriate on such a policy issue, 
nor on the Human Research rule itself. Petitioners' second proffer is a 
legal/policy question regarding the weight to be accorded to existing 
peer review reports. No hearing is required on such issues. To the 
extent the third proffer even constitutes a proffer of ``evidence,'' it 
fails because it is nothing more than a mere allegation. Petitioners 
have supplied no information as to how the HSRB's ``technical'' 
concerns are resolved by the study itself.
    Viewed on their merits, these claims do not convince EPA that it 
erred in determining that the Arnold study did not meet the Human 
Research rule because it lacked scientific validity. EPA concluded, 
based on the advice of the HSRB, that, because the Arnold study had an 
extremely small sample size (2 persons per dose) and highly variable 
measurement of RBC and plasma AChE, it had no scientific value. The 
claim by Petitioners that somehow the Arnold study could be 
rehabilitated by considering it in the context of carbofuran animal 
data misunderstands the issue. The question under the Human Research 
rule is whether the human study at issue is scientifically valid. Here, 
EPA found the Arnold study to be flawed at its core. Animal data on 
carbofuran are simply irrelevant to the problems with sample size and 
AChE measurement in the Arnold study. As to the earlier reports on the 
Arnold study, Petitioners have provided no reason as to why these 
should outweigh the HSRB's conclusion concerning whether the Arnold 
study met the Human Research rule standard. The earlier reports were 
completed well before the Human Research rule was promulgated and thus 
could not have addressed the rule's requirements. Further, the earlier 
reports identified the same defects, but concluded that the Arnold's 
study's flaws could be addressed by the use of additional safety

[[Page 59683]]

factors--an option not available under the Human Research rule. In such 
circumstances, it was reasonable for EPA to give primary weight to the 
HSRB findings. Petitioners' claim that the HSRB only identified 
``technical'' problems with the Arnold study and that the study itself 
addresses the HSRB's concerns is without basis. The flaws in the Arnold 
study are not technical but fundamental, and cannot be explained away. 
Finally, Petitioners' allegations that EPA hampered the HSRB's 
consideration of the prior peer review reports and that EPA's recusal 
decision was somehow improper are contradicted by the record. 
Accordingly, the objection is denied.
    e. Import Tolerance Objection--Issue: Did EPA err by failing to 
retain the carbofuran tolerances that apply solely to imported food. 
Whether EPA had some type of independent duty to retain carbofuran 
tolerances for the imported foods bananas, rice, coffee, and sugarcane 
despite its finding that aggregate exposure to carbofuran is unsafe, is 
a legal question. Hearings are not held on legal issues. Having found 
that aggregate exposure to carbofuran is unsafe, EPA was clearly 
warranted, if not required, to revoke all tolerances. For the policy 
reasons identified above, (see Unit VI.I), when aggregate risk to a 
pesticide is unsafe, EPA defers to interested parties to decide in the 
first instance what tolerances, if any, they wish to retain. Although 
explicitly invited to do so, no person submitted a comment on the 
proposed revocation that identified the import tolerances as a subset 
of tolerances that were asserted to be safe, and that the commenter 
wished to retain. Accordingly, this objection is denied.

K. Conclusion

    For all of the reasons set forth above, EPA denies the Petitioners' 
objections and their requests for a hearing on those objections.

VII. Regulatory Assessment Requirements

    As indicated previously, this action announces the Agency's final 
order regarding objections filed under section 408 of FFDCA. As such, 
this action is an adjudication and not a rule. The regulatory 
assessment requirements imposed on rulemaking do not, therefore, apply 
to this action.

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, (5 U.S.C. 801 et seq.), as added by 
the Small Business Regulatory Enforcement Fairness Act of 1996, does 
not apply because this action is not a rule for purposes of 5 U.S.C. 
804(3).

IX. References

    EPA has established an official record for this rulemaking. The 
official record includes all information considered by EPA in 
developing this proposed rule including documents specifically 
referenced in this action and listed below, any public comments 
received during an applicable comment period, and any other information 
related to this action, including any information claimed as CBI. This 
official record includes all information physically located in docket 
ID number EPA-HQ-OPP-2005-0162, as well as any documents that are 
referenced in the documents listed below or in the docket. The public 
version of the official record does not include any information claimed 
as CBI.
    Objections to the Final Order Revoking Tolerances for Carbofuran, 
and Request for Public Evidentiary Hearing, submitted by National 
Potato Council, National Corn Growers Association, National Cotton 
Council, National Sunflower Association, and FMC Corporation. June 30, 
2009. EPA-HQ-OPP-2005-0162-0578.

Exhibit 1

     FMC's letter of 9-29-08 and accompanying label amendments.

Exhibit 2

     FMC's letter of 12-24-08 and accompanying label 
amendments.

Exhibit 3

     FMC's letter of 6-30-09 and accompanying label amendments.

Exhibit 4

     Expert Report: Carbofuran's FQPA Safety Factor and 
Interspecies Uncertainty Factor by K. Wallace (6 p.)
     13 published articles on pesticide effect on 
cholinesterase activity.

Exhibit 5

     Central Nervous System as the Primary Target for 
Carbofuran's Effects on Lip Smacking by Neal, Williams, & Lamb (3 p.)
     10 published articles on effects of cholinergic 
stimulation.

Exhibit 6

     Expert Report: Carbofuran FQPA Safety Factor by K. Wallace 
(8 p.)
     9 published articles on HBC versus brain cholinesterase 
inhibition.

Exhibit 7

     Dose Response Modeling Issue in Carbofuran by Sielken: 
AChE and BMD Ratios

Exhibit 8

     Dose Response Modeling Issue in Carbofuran by Sielken: 
Statistical Comparison of AChE Inhibition in RBC and Brain in Rats 
Exposed to Carbofuran.

Exhibit 9

     Dose Response Modeling Issue in Carbofuran by Sielken: 
OPP's Estimates of the Half-Life of AChE Recovery.

Exhibit 10

     Reiner, 1971. Spontaneous Reactivation of Phosphorylated 
and Carbamylated Cholinesterases Bulletin WHO 44, 109-112.

Exhibit 11

     Carbofuran Dietary Risk Assessment. 2009. (Exponent Inc., 
for FMC)

Exhibit 12

     Williams, Cheplick, Engle, Fawcett and Hoogeweg. 2009. 
National Carbofuran Leaching Assessment. Vol 1. Waterborne 
Environmental Inc., Engel Consulting, and Fawcett Consulting for FMC.

Exhibit 13

     Williams, Cheplick, Engle, Fawcett and Hoogeweg. 2009. 
National Carbofuran Leaching Assessment. Vol 2. Setback Analysis. 
Waterborne Environmental Inc., Engel Consulting, and Fawcett Consulting 
for FMC.

Exhibit 14

     Memorandum. From: Hoogeweg and Williams, Waterborne, Inc., 
To: Fuge, Latham and Watkins, LLP. June 30, 2009. Subject: Groundwater 
pH in selected states.

Exhibit 15

     Williams, Fawcett and Engle. 2009. The Development and 
Evaluation of a Carbofuran Management Plan to Protect Drinking Water 
Derived from Surface Water Sources. Waterborne Environmental Inc., for 
FMC.

Exhibit 16

     Memorandum. From: Hoogeweg and Williams, Waterborne, Inc., 
To: Fuge, Latham and Watkins, LLP. June 30, 2009. Subject: Surface 
water pH in selected states.

Exhibit 17

     Memorandum. From: Williams, Waterborne, Inc., To: Fuge, 
Latham and Watkins, LLP. June 30, 2009. Subject: Water Treatment 
Assessment in Carbofuran Use States.

[[Page 59684]]

Exhibit 18

     Petition of the National Corn Grower's Association, the 
National Sunflower Association, the National Potato Council, and FMC 
Corporation to Defer the Effective Date of Certain Tolerance 
Revocations for Carbofuran.

References

    1. Acute oral (gavage) dose range-finding study of 
cholinesterase depression from carbofuran technical in juvenile (day 
11) rats. Hoberman, 2007. MRID 47143703 (unpublished FMC study) EPA-
HQ-OPP-2007-1088-0062.
    2. Acute oral (gavage) time course study and final report of 
cholinesterase depression from carbofuran technical in adult and 
juvenile (day 11 postpartum) rats. Hoberman, 2007. MRID 47143704, 05 
(unpublished FMC studies) EPA-HQ-OPP-2007-1088-0063 and -0066.
    3. Acute time-course study of carbofuran technical administered 
by gavage to adult and postnatal day 11 male and female CD (Sprague-
Dawley) rats: Tyl, Marr, and Myers. 2005. (Unpublished study 
received Nov. 14, 2005; prepared by RTI International, RTP, NC; 
submitted by FMC Corp., Philadelphia, Pa.; FMC Study No: A2005-5982. 
MRID 46688913. EPA-HQ-OPP-2005-0162-0058.
    4. Acute dose-response study of carbofuran technical 
administered by gavage to adult and postnatal day 11 male and female 
CD (Sprague-Dawley) rats: Tyl and Myers. 2005. MRID 46688914. EPA-
HQ-OPP-2005-0162-0078.
    5. Anderson, S. A. (2002). The Toxicokinetics of Peripheral 
Cholinesterase Inhibition from Orally Administered Carbofuran in 
Adult Male and Female CD Rats. (Unpublished study received May 15, 
2002; prepared by Toxicokinetics Laboratory, RTP, NC; submitted by 
FMC Corp., Philadelphia, Pa.; FMC Study No: A2001-5379. MRID 456757-
01.
    6. An Investigation into the Potential for Carbofuran Leaching 
to Ground Water Based on Historical and Current Use Practices. 
Submitted by FMC Corporation, Philadelphia, PA.: Report No. PC-0363. 
MRID 47221602. EPA-HQ-OPP-2007-1088-0022.
    7. Arnold, J.D. (1976) Evaluation of the Safe Exposure Levels to 
Carbamate, Administered Orally to Healthy Adult Normal Male 
Volunteers. (Unpublished study received Oct. 24, 1979 under 279- 
2712; prepared by Quincy Research Center, submitted by FMC Corp., 
Philadelphia, Pa.; CDL:241303-B) Accession no. 241303. MRID 
00092826. EPA-HQ-ORD-2006-0310-0020.
    8. Arnold, J.D. (1977) Carbamate (Carbofuran) Human Dermal 
Study. Final rept. (Unpublished study received Oct. 24, 1979 under 
279-2712; prepared by Quincy Research Center, submitted by FMC 
Corp., Philadelphia, Pa.; CDL:241303-C), Accession no. 241303. MRID 
00092827. EPA-HQ-ORD-2006-0310-0020.
    9. Arnold, J.D. (1978) Comparison of Cholinesterase Inhibition 
and Effects of Furadan 4F and FMC 35001 4 EC (ACT 152.03). Rev. 
final rept. (Unpublished study received Oct. 24, 1979 under 279-
2712; prepared by Quincy Research Center, submitted by FMC Corp., 
Philadelphia, Pa.; CDL:241305-A) Accession no. 241305, MRID no. 
00092829. EPA-HQ-ORD-2006-0310-0020.
    10. Benjamins, J.A. and McKhann, G.M. (1981) Development, 
regeneration, and aging of the brain. In: Basic Neurochemistry, 3rd 
edition. Edited by Siegel, G.J., Albers, R.W., Agranoff, B.W., and 
Katzman, R. Little, Brown and Co., Boston. pp 445-469.
    11. Bretaud S, Toutant JP, Saglio P. 2000. Effects of 
carbofuran, diuron, and nicosulfuron on acetylcholinesterase 
activity in goldfish (Carassius auratus). Ecotoxicol Environ Saf. 
2000 Oct.; 47(2):117-24.
    12. Carbofuran Acute Aggregate Dietary (Food and Drinking Water) 
Exposure and Risk Assessments for the Reregistration Eligibility 
Decision (T. Morton, 7/22/08, D351371). EPA-HQ-OPP-2005-0162-0508.
    13. Carbofuran Environmental Risk Assessment and Human Drinking 
Water Exposure Assessment for IRED. March 2006. EPA-HQ-OPP-2005-
0162-0080.
    14. Carbofuran. HED Revised Risk Assessment for the 
Reregistration Eligibility Decision (RED) Document (Phase 6). (PC 
090601) D 330541, July 26, 2006. EPA-HQ-OPP-2005-0162-0307.
    15. Carbofuran. HED Revised Risk Assessment for the Notice of 
Intent to Cancel. (PC 090601) D 347038, January 2007. EPA-HQ-OPP-
2007-1088-0034.
    16. Carr, Chambers, Guarisco, Richardson, Tang, and Chambers. 
2001. Effects of repeated oral postnatal exposures to chlorpyrifos 
on open-field behavior in juvenile rats. Toxicol. Sci. 59: 260-267.
    17. Chen, W.L., Sheets, Nolan and Mattson. 1999. Human red blood 
cell acetylcholinesterase inhibition as the appropriate and 
conservative surrogate endpoint for establishing chlorpyrifos 
refernce dose. Regul. Toxicol. 'Pharmacol. 29, 15-22.
    18. Comments in Opposition to Proposed Tolerance Revocations for 
Carbofuran. (September 29, 2008). Submitted by the National Potato 
Council, National Corn Growers Association, National Cotton Coucil, 
National Sunflower Association, and FMC Corporation. EPA-HQ-OPP-
2005-0162-0547.1.
    19. Costa, Hand, Schwab, and Murphy. 1981a. Reduced [3H] 
quinuclidinyl benzilate binding to muscarinic receptors in 
disulfoton-tolerant mice. Toxicol. Appl. Pharmacol. 60: 441-450.
    20. Costa, Hand, Schwab, and Murphy. 1981b. Tolerance to the 
carbamate insecticide propoxur. Toxicology. 21: 267-278.
    21. Costa and Murphy. 1983. Unidirectional cross-tolerance 
between the carbamate insecticide propoxur and the organophosphate 
disulfoton in mice. Fund. Appl. Toxicol. 3: 483-488.
    22. Davison, A.N. and Dobbing, J. (1966) Myelination as a 
vulnerable period in brain development. Br. Med. Bull. 22: 40-44.
    23. Dobbing, J. and Smart, J.L. (1974) Vulnerability of 
developing brain and behaviour. Br. Med. Bull. 30: 164-168;
    24. Dose-Time Response Modeling of Rat Brain AChE Activity: 
Carbofuran Gavage Dosing: BMD50s for PND11 
animals, January 14, 2009. EPA-HQ-OPP-2005-0162-0571.
    25. Dose-Time Response Modeling of Rat RBC AChE Activity: 
Carbofuran Gavage Dosing: BMD50s for PND11 
Animals, January 14, 2009. EPA-HQ-OPP-2005-0162-0570.
    26. El-Naggar AEl-R, Abdalla MS, El-Sebaey AS, Badawy SM. (2009) 
Clinical findings and cholinesterase levels in children of 
organophosphates and carbamates poisoning. Eur. J. Pediatrics 168: 
951-956.
    27. Engel, Bernard, Richard S. Fawcett, and W. Martin Williams. 
2008. Comments to the FIFRA Scientific Advisory Panel--Volume V.: 
The Water Risk Assessment for Carbofuran. From Carbofuran Scientific 
Advisory Panel Meeting, Feb. 5-8, 2008, Docket ID Number: EPA-HQ-
OPP-2007-1088 FMC Corporation, Agricultural Products Group Written 
Comments.
    28. EPA Response to the Transmittal of Meeting Minutes of the 
FIFRA Scientific Advisory Panel Meeting Held February 5-8 2008 on 
the Agency's Proposed Action under FIFRA 6(b) Notice of Intent to 
Cancel Carbofuran (E. Reaves, A. Lowit, J. Liccione 7/2008 D352315). 
EPA-HQ-OPP-2005-0162-0505.
    29. Fawcett, R., B. Engel, W. Williams. 2007. An Investigation 
into the Potential for Carbofuran Leaching to Ground Water Based on 
Historical and Current Product Uses. (MRID 47221602) Project Number 
PC/0363. 32 p. EPA-HQ-OPP-2005-0162-0454.1
    30. FIFRA SAP (1998) ``A set of Scientific Issues Being 
Considered by the Agency in Connection with Proposed Methods for 
Basin-scale Estimation of Pesticide Concentrations in Flowing Water 
and Reservoirs for Tolerance Reassessment.'' Final Report from the 
FIFRA Scientific Advisory Panel Meeting of July 29-30, 1998 (Report 
dated September 2, 1998). Available at: http://www.epa.gov/scipoly/
sap/meetings/1998/july/final1.pdf.
    31. FIFRA SAP (1999) ``Sets of Scientific Issues Being 
Considered by the Environmental Protection Agency Regarding Use of 
Watershed-derived Percent Crop Areas as a Refinement Tool in FQPA 
Drinking Water Exposure Assessments for Tolerance Reassessment.'' 
Final Report from the FIFRA Scientific Advisory Panel Meeting of 
February 5-7, 2002 (Report dated May 25, 1999). SAP Report 99-03C. 
Available at: http://www.epa.gov/scipoly/sap/meetings/1999/may/
final.pdf.
    32. SAP. 2001a. REPORT: FIFRA Scientific Advisory Panel Meeting, 
September 29, 2000, held at the Sheraton Crystal City Hotel, 
Arlington, Virginia. Session VI-A Set of Scientific Issues Being 
Considered by the Environmental Protection Agency Regarding: 
Progress Report on Estimating Pesticide Concentrations in Drinking 
Water and Assessing Water Treatment Effects on Pesticide Removal and 
Transformation: A Consultation. SAP Report No 2002-2.
    33. FIFRA SAP. (2002a). ``Methods Used to Conduct a Preliminary 
Cumulative Risk Assessment for Organophosphate Pesticides.'' Final 
Report from the FIFRA Scientific Advisory Panel Meeting of February 
5-7, 2002 (Report dated March 19, 2002). FIFRA Scientific Advisory 
Panel, Office of Science Coordination and Policy, Office of 
Prevention, Pesticides and Toxic Substances, U.S. Environmental 
Protection

[[Page 59685]]

Agency. Washington, DC. SAP Report 2002-01.
    34. FIFRA Science Advisory Panel (SAP). 2005a. ``Final report on 
N-Methyl Carbamate Cumulative Risk Assessment: Pilot Cumulative 
Analysis.'' Final Report from the FIFRA Scientific Advisory Panel 
Meeting of February, 2005 (Report dated September 2, 1998). 
Available at: http://www.epa.gov/scipoly/sap/2005/february/
minutes.pdf.
    35. FIFRA Science Advisory Panel (SAP). 2005b. ``Final report on 
Preliminary N-Methyl Carbamate Cumulative Risk Assessment.'' Final 
Report from the FIFRA Scientific Advisory Panel Meeting of July 29-
30, 1998 (Report dated September 2, 1998). Available at: http://
www.epa.gov/scipoly/sap/2005/august/minutes.pdf.
    36. FIFRA Science Advisory Panel (SAP). 2008. ``Final report on 
the Agency's Proposed Action under FIFRA 6(b) Notice of Intent to 
Cancel Carbofuran.'' Report from the FIFRA Scientific Advisory Panel 
Meeting of February, 5-8 2008 (Report dated September 2, 1998). 
Available at: http://www.epa.govscipoly/sap/meetings/2008/february/
carbofuransapfinal.pdf.
    37. Hoberman, A. M. (1998). Developmental Neurotoxicity Study of 
Chlorpyrifos Administered Orally via Gavage to Crl:CDBR VAF/Plus 
Presumed Pregnant Rats. EPA--MRID No. 44556901. Dow Chemical Co., 
Midland, MI.
    38. HSRB Meeting Minutes. June 1, 2006. Minutes of the United 
States Environmental Protection Agency (EPA) Human Studies Review 
Board (HSRB) May 2-3, 2006 Public Meeting Docket Number: EPA-HQ-ORD-
2006-0310. http://www.epa.gov/osa/hsrb/files/meeting-materials/may-
2-3-2006-public-meeting/mayminutesfinal.pdf.
    39. HSRB Memorandum: Farland to HSRB Board. May 1, 2006 ``Ethics 
Determination for Participation at the May 2-3, 2006 EPA Human 
Studies Review Board Meeting.''
    40. HSRB Report. July 7, 2006. Memorandum from Fisher to Gray. 
Subject: May 2-3, 2006 EPA Human Studies Review Board Meeting 
Report. http://www.epa.gov/osa/hsrb/files/meeting-materials/may-2-3-
2006-public-meeting/final7706.pdf.
    41. Hunter, D. L., Lassiter, T. L., and Padilla, S. 1999. 
Gestational exposure to chlorpyrifos: comparative distribution of 
trichloropyridinol in the fetus and dam. Toxicol. Appl. Pharmacol. 
158, 16-23.
    42. Issue Paper for the FIFRA SAP Meeting on Carbofuran: Human 
Health Risk Assessment Reregistration Eligibility Science Chapter 
for Carbofuran, Environmental Fate and Effects Chapter. March 2006. 
EPA-HQ-OPP-2007-1088-0031.
    43. Jones, R. David, Sidney Abel, William Effland, Robert 
Matzner, and Ronald Parker. 1998. Proposed Methods for Basin-scale 
Estimation of Pesticide Concentrations in Flowing Water and 
Reservoirs for Tolerance Reassessment: Chapter IV., An Index 
Reservoir for Use in Assessing Drinking Water Exposure. Presentation 
to the FIFRA Science Advisory Panel, July 29-30, 1998.
    44. Jones, R. David. 2007a. Additional chemographs for potatoes 
and cucurbits for drinking water exposure assessment in support of 
the reregistration of carbofuran. Internal EPA Memorandum to Jude 
Andreasen and Danette Drew dated October 23, 2007. EPA-HQ-OPP-2005-
0162-0486.
    45. Jones, R. David. 2007b. Summary Evaluation of Recently 
Submitted FMC Water Exposure Studies. (DP 347901) Internal EPA 
Memorandum to Jude Andreasen dated December 26, 2007. Available in 
the federal docket at www.regulations.gov at EPA-HQ-OPP-2007-1088-
0016.
    46. Jones, R. David (2008a) (5/1/2008). Additional refinements 
for estimations of drinking water exposure from carbofuran use on 
corn. (DP 351653). EPA-HQ-OPP-2005-0162-0569.
    47. Jones, R. David. 2008b. Additional Refinements of the 
Drinking Water Exposure Assessment for the Use of Carbofuran on Corn 
and Melons. (DP 353714) Internal EPA Memorandum to Jude Andreasen 
and Thurston Morton, dated June 23, 2008. EPA-HQ-OPP-2005-0162-0510.
    48. Jones, R. David. (2008c) Updated Refinements of the Drinking 
Water Exposure Assessment for the Use of Carbofuran on Corn and 
Melons, 8/18/2008. (DP 355584) Internal EPA Memorandum to Jude 
Andreasen and Thurston Morton, dated August 18, 2008. EPA-HQ-OPP-
2005-0162-0516.
    49. Lauzon, John D., Ivan P. O'Halloran, David J. Fallow, A. 
Peter von Bertoldi, and Doug Aspinall. 2005. Spatial Variability of 
Soil Test Phosphorus, Potassium, and pH of Ontario Soils. Agronomy 
Journal 97:524-532.
    50. Lifshitz, Shahak, Bolotin, and Sofer. 1997. Carbamate 
Poisoning in Early Childhood and in Adults. Clinical Toxicology. 35: 
25-27.
    51. Marable BR, Maurissen JP, Mattsson JL, Billington R. 2007. 
Differential sensitivity of blood, peripheral, and central 
cholinesterases in beagle dogs following dietary exposure to 
chlorpyrifos. Regul Toxicol Pharmacol. 2007 Apr;47(3):240-8.
    52. Mattsson, J. L., Maurissen, J. P., Nolan, R. J., and Brzak, 
K. A. 2000. Lack of differential sensitivity to cholinesterase 
inhibition in fetuses and neonates compared to dams treated 
perinatally with chlorpyrifos. Toxicol Sci 53, 438-46.
    53. McDaniel K.L. and Moser V.C. (2004) Differential profiles of 
cholinesterase inhibition and neurobehavioral effects in rats 
exposed to fenamiphos or profenofos. Neurotoxical Teratol. 26:407-
415.
    54. McDaniel K.L., Padilla S., Marshall R.S., Phillips P.M., 
Podhorniak L., Qian Y., Moser V.C. (2007) Comparison of acute 
neurobehavioral and cholinesterase inhibitory effects of N-methyl 
carbamates in rats. Toxicol. Sci. 98, 552-560.
    55. Morton, T., 4/29/09, D358037, Carbofuran Acute Aggregate 
Dietary (Food and Drinking Water) Exposure and Risk Assessments for 
the Reregistration Eligibility Decision.
    56. Moser V.C. (1995) Comparisons of the acute effects of 
cholinesterase inhibitors using a neurobehavioral screening battery 
in rats. Neurotoxical Teratol 17: 617-625.
    57. National Assessment of the Relative Vulnerability of 
Community Water Supply Reservoirs in Carbofuran Use Areas. Performed 
by Waterborne Environmental Inc., Leesburg, VA and Engel Consulting, 
West Lafayette, IN. Submitted by FMC Corporation, Philadelphia, PA. 
WEI Report No. 528.01-B, FMC Report No. PC-0387. MRID 47272301. EPA-
HQ-OPP-2007-1088-0024.
    58. National Resources Inventory 1992, cited in USGS 2002, 
``Herbicide Concentrations in the Mississippi River Basin--the 
importance of chloracetanilide degradates.'' R.A. Rebich, R.H. 
Coupe, E.M.Thurman.
    59. Nostrandt, A.C., Padilla, S., and Moser, V.C. (1997). The 
relationship of oral chlorpyrifos effects on behavior, 
cholinesterase inhibition, and muscarinic receptor density in rat. 
Pharmacol. Biochem. Behav. 58, 15-23.
    60. Ott, Wayne R. 1995. Environmental Statistics and Data 
Analysis. CRC Press. Boca Raton, Florida.
    61. Padilla S, Marshall RS, Hunter DL, Oxendine S, Moser VC, 
Southerland SB, Mailman RB. 2005. Neurochemical effects of chronic 
dietary and repeated high-level acute exposure to chlorpyrifos in 
rats. Toxicol Sci. 2005 Nov;88(1):161-71.
    62. Padilla S., Marshall R.S., Hunter D.L., and Lowit A. 2007. 
Time course of cholinesterase inhibition in adult rats treated 
acutely with carbaryl, carbofuran, formetanate, methomyl, 
methiocarb, oxamyl, or propoxur. Toxicology and Applied 
Pharmacology, 219; 202-209.
    63. PND17 BMDs and BMDLs and recovery half-lives for the effects 
of carbofuran on brain and blood AChE (PND17--DR.pdf). EPA-HQ-OPP-
2007-1088-0047.
    64. Richardson, J., and Chambers, J. (2003). Effects of 
gestational exposure to chlorpyrifos on postnatal central and 
peripheral cholinergic neurochemistry. J Toxicol Environ Health A 
66, 275-89.
    65. Richardson, J., and Chambers, J. 2005. Effects if repeated 
oral postnatal exposure to chlorpyrifos on cholinergic 
neurochemistry in developing rats. Toxicol Sci 84, 352-59.
    66. Report on cholinesterase sensitivity study of carbofuran: 
Adult and PND11 MRID 47289001 (ORD study). EPA-HQ-OPP-2007-1088-
0065.
    67. Revised Drinking Water Assessment in Support of the 
Reregistration of Carbofuran (PC Code 090601) (R. David Jones, 9/5/
07 D3424057). EPA-HQ-OPP-2005-0162-0485.
    68. Rupniak, NM, Jenner, P and Marsden, CD. 1983. Cholinergic 
manipulation of perioral behaviour induced by chronic neuroleptic 
administration to rats. Psychopharmacology 79 (2-3): 226-230.
    69. Screening Level analysis of the small business impacts of 
revoking carbofuran tolerances. (Wyatt, T.J. July 2008) 28 pgs. EPA-
HQ-OPP-2005-0162-0506.
    70. Setzer W. October 5, 2007. Dose-time response modeling of 
rat brain AChE activity: Carbofuran gavage dosing. 64 pgs. EPA-HQ-
OPP-2007-1088-0053.
    71. Schwab, Hand, Costa and Murphy. 1981. Reduced Muscarinic 
Receptor Binding in Tissues of Rats Tolerant to the Insecticide 
Disulfoton. Neurotoxicology. 2: 635-647.
    72. Somani, S. M. and Dube, S. N. 1989. In vivo dose response 
relationship between physostigmine and cholinesterase activity in 
RBC and tissues of rat. Life Science 44, 1907-1915.
    73. Thelin, Gail P., and Leonard P. Gianessi. 2000. Method for 
Estimating

[[Page 59686]]

Pesticide Use for County Areas of the Conterminous United States. 
U.S. Geological Survey Open-File Report 00-250. Sacramento, 
California, 2000. Available at: http://water.usgs.gov/nawqa/pnsp/
pubs/ofr00250.
    74. Trask, Jennifer R., and Joshua Amos. 2005. Watershed 
Regressions for Pesticides (WARP) for Carbofuran in Illinois 
Watersheds. Prepared by Waterborne Environmental Inc., Leesburg, VA. 
WEI 362.07. (MRID 46688915) Submitted by FMC Corporation, 
Philadephia, PA FMC Study P3786. EPA-HQ-OPP-2005-0162-0061.
    75. USEPA (2000a) ``Assigning Values to Nondetected/
Nonquantified Pesticide Residues in Human Health Dietary Exposure 
Assessments.'' March 23, 2000. Available at: http://www.epa.gov/
pesticides/trac/science/trac3b012.pdf.
    76. USEPA. (2000b). ``Benchmark Dose Technical Guidance 
Document.'' Draft report. Risk Assessment Forum, Office of Research 
and Development, U.S. Environmental Protection Agency. Washington, 
DC. EPA/630/R-00/001.
    77. USEPA. (2000c) ``Choosing a Percentile of Acute Dietary 
Exposure as a Threshold of Regulatory Concern.'' March 16, 2000. 
Available at: http://www.epa.gov/pesticides/trac/science/
trac2b054.pdf.
    78. USEPA. (2000d). ``The Use of Data on Cholinesterase 
Inhibition for Risk Assessments of Organophosphorous and Carbamate 
Pesticides.'' August 18, 2000. Available at: http://www.epa.gov/
pesticides/trac/science/cholin.pdf.
    79. USEPA. (2002). ``Office of Pesticide Programs' Policy on the 
Determination of the Appropriate FQPA Safety Factor(s) For Use in 
Tolerance Assessment.'' Available at: http://www.epa.gov/oppfead1/
trac/science/determ.pdf.
    80. USEPA Peer Review Handbook 3rd Edition. 2006. Prepared for 
the U.S. Environmental Protection Agency by Members of the Peer 
Review Advisory Group, for EPA's Science Policy Council http://
www.epa.gov/peerreview/.
    81. USEPA (2007a). ``Revised N-Methyl Carbamate Cumulative Risk 
Assessment U.S. Environmental Protection Agency, Office of Pesticide 
Programs,'' September 24, 2007. Available at: http://www.epa.gov/
oppsrrd1/REDs/nmc_revised_cra.pdf.
    82. USEPA (2007b). Carbaryl. HED Chapter of the Reregistration 
Eligibility Decision Document (RED). PC Code: 056801, DP Barcode: 
D334770. 28 June 2007. EPA-HQ-OPP-2007-0941-0003.
    83. U.S. Environmental Protection Agency. 2008a. EPA response to 
the transmittal of meeting minutes of the FIFRA Scientific Advisory 
Panel Meeting held February 5-8 on the Agency's proposed action 
under FIFRA 6(b) Notice of Intent to Cancel Carbofuran (3-26-08). E. 
Reaves et al., July 22, 2008, DP 352315. EPA-HQ-OPP-2005-0162-0505.
    84. USEPA (2009a) Jones, R. David, Reuben Baris, and Marietta 
Echeverria. 2009. Response to comments on EPA's proposed tolerance 
revocations for carbofuran specifically related to drinking water 
exposure assessment. Internal EPA memorandum to Jude Andreasen dated 
April 29, 2009. D362182. EPA-HQ-OPP-2005-0162-0565.
    85. USEPA (2009b) Response to Comments in Opposition to Proposed 
Tolerance Revocations for Carbofuran Docket EPA-HQ-OPP-2005-0162'' 
submitted by the National Potato Council, National Corn Growers 
Association, National Cotton Council, National Sunflower 
Association, and FMC Corporation (September 29, 2008). April 29, 
2009. EPA-HQ-OPP-2005-0162-0567.
    86. Watershed Regressions for Pesticides (WARP) Model Estimates 
for Carbofuran in Illinois Watershed. Performed by Waterborne 
Environmental, Inc., Leesburg, VA. WEI 362.07. Submitted by FMC 
Corporation, Philadelphia, PA. Report No. P-3786. MRID 46688915. 
EPA-HQ-OPP-2007-1088-0021.
    87. WHO JMPR, 1999. FAO/WHO Joint Meeting on Pesticide Residues. 
Report of the 1998 FAO/WHO Joint Meeting on Pesticide Residues. Food 
and Agriculture Organization-United Nations. Rome, Italy. http://
www.fao.org.
    88. Whyatt, R., Barr, D., Camann, D., Kinney, P., Barr, J., 
Andrews, H., et al. (2003). Contemporary-use pesticides in personal 
air samples during pregnancy and blood samples at delivery among 
urban minority mothers and newborns. Environmental Health 
Perspectives, vol. 111, num. 5, pp. 749-756.
    89. Williams, W. M., (2007a) B. Engel, S. Dasgupta, and C. G. 
Hoogeweg. An In-Depth Investigation to Estimate Surface Water 
Concentrations of Carbofuran within Indiana Community Water 
Supplies. (MRID 47221603) Performed by Waterborne Environmental, 
Inc., Leesburg, VA, Engel Consulting, and Fawcett Consulting. 
Submitted by FMC Corporation, Philadelphia, PA. WEI No 528.01, FMC 
Report No. PC-0378. EPA-HQ-OPP-2005-0162-0453.
    90. Williams, W. M. (2007b) B. Engel, J. Amos, and C. G. 
Hoogeweg. National Assessment of the Relative Vulnerability of 
Community Water Supply Reservoirs in Carbofuran Use Areas. (MRID 
47272301) Performed by Waterborne Environmental, Inc.and Engel 
Consulting. Submitted by FMC Corporation, Philadelphia, PA. EPA-HQ-
OPP-2005-0162-0463.
    91. Zwiener RJ, Ginsburg CM. (1988) Organophosphate and 
carbamate poisoning in infants and children. Pediatrics 81:121-126.
    92. Vecchia, A.V. and Crawford, C. G. (2006). Simulation of 
Daily Pesticide Concentrations From Watershed Characteristics and 
Monthly Climatic Data USGS Scientific Investigations. USGS Report 
2006-5181. 60 pgs.

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: October 30, 2009.
Debra Edwards,
Director, Office of Pesticide Programs.
[FR Doc. E9-27261 Filed 11-17-09; 8:45 am]

BILLING CODE 6560-50-P
