
[Federal Register Volume 76, Number 66 (Wednesday, April 6, 2011)]
[Rules and Regulations]
[Pages 18915-18921]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-8024]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2009-0493; FRL-8863-1]


Ethiprole; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes permanent tolerances (without U.S. 
registrations) for residues of the insecticide ethiprole [5-amino-1-
[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(ethyl)-sulfinyl]-1H-
pyrazole-3-carbonitrile], including its metabolites and degradate, in 
or on rice and tea. Bayer CropScience LP requested these tolerances 
under the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective April 6, 2011. Objections and 
requests for hearings must be received on or before June 6, 2011, and 
must be filed in accordance with the instructions provided in 40 CFR 
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: EPA has established a docket for this action under docket 
identification (ID) number EPA-HQ-OPP-2009-0493. All documents in the 
docket are listed in the docket index available at http://www.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: Carmen Rodia, Registration Division, 
Office of Pesticide Programs, Environmental Protection Agency, 1200 
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: 
(703) 306-0327; e-mail address: rodia.carmen@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to, 
those engaged in the following activities:
     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 to 
provide 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 get electronic access to other related information?

    You may access a frequently updated electronic version of EPA's 
tolerance regulations at 40 CFR part 180 through the Government 
Printing Office's e-CFR site at http://www.gpoaccess.gov/ecfr.

C. How can I file an objection or hearing request?

    Under section 408(g) of FFDCA, 21 U.S.C. 346a, any person may file 
an objection to any aspect of this regulation and may also request a 
hearing on those

[[Page 18916]]

objections. You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in 40 CFR part 
178. To ensure proper receipt by EPA, you must identify docket ID 
number EPA-HQ-OPP-2009-0493 in the subject line on the first page of 
your submission. All objections and requests for a hearing must be in 
writing, and must be received by the Hearing Clerk on or before June 6, 
2011. Addresses for mail and hand delivery of objections and hearing 
requests are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing that does not contain any CBI for inclusion in the public 
docket. Information not marked confidential pursuant to 40 CFR part 2 
may be disclosed publicly by EPA without prior notice. Submit a copy of 
your non-CBI objection or hearing request, identified by docket ID 
number EPA-HQ-OPP-2009-0493, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P), 
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South 
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only 
accepted during the Docket Facility's normal hours of operation (8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays). 
Special arrangements should be made for deliveries of boxed 
information. The Docket Facility telephone number is (703) 305-5805.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of August 19, 2009 (74 FR 41898) (FRL-8426-
7), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
9E7550) by Bayer CropScience LP, P.O. Box 12014, 2 T.W. Alexander Dr., 
Research Triangle Park, NC 27709-2014. The petition requested that 40 
CFR part 180 be amended by establishing permanent tolerances for 
residues of the insecticide ethiprole [5-amino-1-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-4-[(ethyl)-sulfinyl]-1H-pyrazole-3-
carbonitrile], expressed as parent equivalent, in or on cattle, fat at 
0.1 parts per million (ppm); cattle, liver at 0.1 ppm; cattle, meat at 
0.01 ppm; cattle, meat byproducts, except liver at 0.02 ppm; eggs at 
0.05 ppm; goat, fat at 0.1 ppm; goat, liver at 0.1 ppm; goat, meat at 
0.01 ppm; goat, meat byproducts, except liver at 0.02 ppm; hog, fat at 
0.1 ppm; hog, liver at 0.1 ppm; hog, meat at 0.01 ppm; hog, meat 
byproducts, except liver at 0.02 ppm; horse, fat at 0.1 ppm; horse, 
liver at 0.1 ppm; horse, meat at 0.01 ppm; horse, meat byproducts, 
except liver at 0.02 ppm; milk at 0.01 ppm; poultry, fat at 0.1 ppm; 
poultry, meat at 0.01 ppm; poultry, meat byproducts at 0.05 ppm; rice, 
grain at 3.0 ppm; sheep, fat at 0.1 ppm; sheep, liver at 0.1 ppm; 
sheep, meat at 0.01 ppm; sheep, meat byproducts, except liver at 0.02 
ppm; and tea, dried at 50 ppm. That notice referenced a summary of the 
petition prepared by Bayer CropScience LP, the registrant, which is 
available in the docket, http://www.regulations.gov. There were no 
comments received in response to the notice of filing.
    Based upon review of the data supporting the petition, EPA has 
modified a number of the petitioned-for tolerances for ethiprole. The 
reasons for these changes are explained in Unit IV.C.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of 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)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue.''
    Consistent with section 408(b)(2)(D) of FFDCA, and the factors 
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure for ethiprole, including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with ethiprole 
follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children.
    Ethiprole has a low acute toxicity via the acute oral, dermal, and 
inhalation routes of exposure, and is not a skin sensitizer nor a skin 
or eye irritant. In the mammalian toxicology database, the critical 
effects of ethiprole are hepatoxicity and thyroid toxicity. The rat was 
the most sensitive species overall after administration of ethiprole. 
Evidence of hepatoxicity is seen in the 28-day mouse and rat; 90-day 
rat and dog; chronic/carcinogenicity rat and mouse; 2-generation rat; 
developmental rat; and subchronic neurotoxicity rat studies, and was 
manifested as increased liver weight and hepatocellular hypertrophy. 
Other indicators of hepatotoxicity include:
    1. Increased prothrombin time as observed in the 28- and 90-day rat 
studies; and
    2. Changes in clinical chemistry such as increased alanine 
transaminase activity, increased alkaline phosphates activity, 
increased cholesterol, increased triglycerides, and increased total 
protein concentration.
    Liver toxicity was also observed within the mice chronic/
carcinogenicity study. A statistically significant increased incidence 
(12%) of hepatocellular adenoma (HCA) was observed in females at the 
highest dose tested (HDT), when compared to controls (6/50 vs. 0/50). 
These benign tumors were only observed in high dose females where a 
reduced survival rate was also observed. Since no treatment-related HCA 
were reported at the lower dose levels, the dose-dependent effect could 
not be established. In addition, no hepatocellular carcinoma was noted 
in either sex. Given the lack of genotoxicity potential, the absence of 
carcinoma following a prolonged exposure to ethiprole, and the absence 
of any dose relationship, this increased incidence of HCA in high dose 
female mice was, therefore, considered to be due to a threshold 
mechanism with a probable phenobarbital-like action hepatocellular 
hypertrophy associated

[[Page 18917]]

with transient liver cell proliferation followed by a steady state.
    Thyroid toxicity was also observed in numerous studies throughout 
the ethiprole database. These studies include the 28- and 90-day rat; 
chronic/carcinogenicity rat; 2-generation rat; and subchronic 
neurotoxicity rat studies. The results/observations of the 3 
mechanistic studies conducted in rats suggest that ethiprole exerts 
effect by inducing hepatic microsomal enzymes (e.g., T4-glucuronyl 
transferase). This mechanism can lower the circulating levels of 
thyroid hormones (T4 and T3), resulting in a release from negative 
feedback inhibition and a compensatory increased secretion of thyroid 
stimulating hormone (TSH) by the pituitary gland. This negative 
feedback loop results in increased TSH levels to compensate for the 
reduced T4 blood levels, since glucuronyl transferase in the liver is 
conjugating and removing T4 via the bile. The chronic hypersecretion of 
TSH predisposes the sensitive rodent thyroid gland to develop an 
increased incidence of focal hyperplasic and neoplasic (adenomas) 
lesions by a secondary (epigenetic) mechanism. The thyroid toxicity 
observed in adult rodents was manifested as increased thyroid weight, 
thyroid follicular hyperthrophy along with higher TSH plasma levels, 
and reduced T4 (thyroxine) plasma levels. A study that evaluates 
homeostasis and the developing nervous system in the young is not 
available.
    Based on a battery of mutagenicity studies, ethiprole is not 
considered to be genotoxic. In accordance with the EPA's Final 
Guidelines for Carcinogen Risk Assessment (March 2005), ethiprole is 
classified as ``Suggestive Evidence of Carcinogenic Potential.'' This 
classification is based on benign liver tumors in female mice, and 
benign thyroid tumors in male rats. While the evidence from animal data 
is suggestive of carcinogenicity, a cancer risk to humans from dietary 
exposure to ethiprole is of low concern and the cRfD is deemed 
protective of any potential cancer risk based on the following weight-
of-evidence considerations:
    1. The liver tumors in mice were benign with no progression to 
malignancy;
    2. The thyroid tumors in rats were also benign (with no progression 
to malignancy), and the increase in the tumor incidences at the high 
dose did not reach statistical significance when compared to controls;
    3. In both species (mice and rats), tumors were observed only at 
the HDT (i.e., there was a lack of evidence of a dose-response 
relationship);
    4. There is no concern for mutagenicity/genotoxicity;
    5. The no-observed-adverse-effect-level (NOAEL) of 0.85 milligrams/
kilograms/day (mg/kg/day) used for deriving the cRfD is approximately 
86-fold lower than the dose (73 mg/kg/day) that induced benign tumors 
in mice; and
    6. The retention of the 10x FQPA SF yields a chronic Population 
Adjusted Dose (cPAD) that provides even more protection for non-cancer 
dietary risk (i.e., the cPAD of 0.003 mg/kg/day is approximately 2,400-
fold lower than the dose at which tumors were seen).
    Thus, for all these reasons, the Agency has determined that the 
cPAD will adequately account for all chronic effects, including 
carcinogenicity, likely to result from exposure to ethiprole.
    More detailed information on the studies received and the nature of 
the adverse effects caused by ethiprole as well as the NOAEL and the 
LOAEL from the toxicological studies can be found in the document 
entitled, ``Ethiprole: Human Health Risk Assessment for Proposed Uses 
on Imported Rice and Tea,'' dated December 1, 2010, by going to http://www.regulations.gov. The referenced document is available in the docket 
established by this action, which is described under ADDRESSES. Locate 
and click on the hyperlink for docket ID number EPA-HQ-OPP-2009-0493. 
Double-click on the document to view the referenced information on 
pages 13-20 of 60.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern (LOC) to use in evaluating the risk posed by human exposure to 
the pesticide. For hazards that have a threshold below which there is 
no appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which the NOAEL and the lowest-observed-adverse-
effect-level (LOAEL). Uncertainty/safety factors are used in 
conjunction with the POD to calculate a safe exposure level--generally 
referred to as a population-adjusted dose (PAD) or a reference dose 
(RfD)--and a safe margin of exposure (MOE). For non-threshold risks, 
the Agency assumes that any amount of exposure will lead to some degree 
of risk. Thus, the Agency estimates risk in terms of the probability of 
an occurrence of the adverse effect expected in a lifetime. For more 
information on the general principles EPA uses in risk characterization 
and a complete description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
    The acute and chronic dietary endpoints were not harmonized with 
Canada's Pesticide Management Regulatory Agency (PMRA) due to policy 
differences. For both endpoints, PMRA chose the prenatal developmental 
toxicity study in rabbits as their POD. PMRA considered this endpoint 
to be protective of all populations, including pregnant women and their 
fetuses. EPA did not choose the prenatal developmental toxicity study 
in rabbits for the acute dietary endpoint as the observed increased 
incidence of abortions in the dams occurred from days 21 to 28 days of 
gestation, and was not considered to be a single dose (acute) effect 
since it did not occur within 1 to 2 days of dosing. In addition, EPA 
did not rely on the prenatal developmental toxicity in rabbits for the 
chronic dietary assessment since it is not a long-term study. Instead, 
EPA relied on the combined chronic/carcinogenicity oral (dietary) 
toxicity rat study in which thyroid and liver toxicity were observed at 
3.21 mg/kg/day with a NOAEL of 0.85 mg/kg/day. This chronic rat study 
is protective of the effects observed in the rabbit developmental study 
selected by Canada's PMRA. A summary of the toxicological endpoints for 
ethiprole used for human health risk assessment is shown in the table 
of this unit.

[[Page 18918]]



    Table--Summary of Toxicological Doses and Endpoints for Ethiprole for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                     Point of departure and
         Exposure/scenario              uncertainty/FQPA     RfD, PAD, LOC for risk    Study and toxicological
                                         safety factors            assessment                  effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary (All Populations,      NOAEL = 35 mg/kg/day..  Acute RfD = 0.35 mg/kg/ Acute Neurotoxicity
 including Infants, Children, and    UFA = 10x.............   day.                    (dietary) in Rats. LOAEL =
 Females, 13-49 years of age).       UFH = 10x.............  aPAD = 0.035 mg/kg/day   250 mg/kg/day, based on
                                     FQPA SF = UFDB = 10x..                           increased tremors
                                                                                      (females), decreased
                                                                                      grooming (both sexes),
                                                                                      decreased arousal alert
                                                                                      (females), increased
                                                                                      number of animals for
                                                                                      which no assessment of
                                                                                      gait was possible
                                                                                      (females), increased eye
                                                                                      closure (females),
                                                                                      increased standing/sitting
                                                                                      hunched (females),
                                                                                      deceased activity and
                                                                                      rearing counts (females),
                                                                                      increased hindlimb and
                                                                                      forelimb grip strength
                                                                                      (males), decreased
                                                                                      forelimb grip strength
                                                                                      (day 8) (females),
                                                                                      decreased splay (females,
                                                                                      day 1), and increased
                                                                                      splay (males, day 8).
----------------------------------------------------------------------------------------------------------------
Chronic Dietary (All Populations)..  NOAEL= 0.85 mg/kg/day.  Chronic RfD = 0.03 mg/  Combined Chronic/
                                     UFA = 3x..............   kg/day.                 Carcinogenicity Oral
                                     UFH = 10x.............  cPAD = 0.003 mg/kg/day   (dietary) Toxicity in
                                     FQPA SF = UFDB = 10x..                           Rats. LOAEL = 3.21/4.40 mg/
                                                                                      kg/day M/F, based on
                                                                                      observed effects in the
                                                                                      thyroid and/or liver
                                                                                      (histopathologic changes,
                                                                                      increased organ weights,
                                                                                      and/or altered thyroid
                                                                                      hormone or bilirubin
                                                                                      levels).
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, Dermal, Inhalation)..  Suggestive Evidence of Carcinogenicity. Quantification of cancer risk using
                                      a cancer potency factor is not needed. The cRfD is protective of potential
                                                                     cancer risk.
----------------------------------------------------------------------------------------------------------------
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data
  and used to mark the beginning of extrapolation to determine risk associated with lower environmentally
  relevant human exposures. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies).
  UFH = potential variation in sensitivity among members of the human population (intraspecies). UFDB = to
  account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD =
  population adjusted dose (a = acute, c = chronic).

    More detailed information on the toxicological endpoints for 
ethiprole can be found in the document entitled, ``Ethiprole: Human 
Health Risk Assessment for Proposed Uses on Imported Rice and Tea,'' 
dated December 1, 2010, by going to http://www.regulations.gov. The 
referenced document is available in the docket established by this 
action, which is described under ADDRESSES. Locate and click on the 
hyperlink for docket ID number EPA-HQ-OPP-2009-0493. Double-click on 
the document to view the referenced information on page 21 of 60.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to ethiprole, EPA considered exposure under the petitioned-for 
tolerances. Acute and chronic dietary (food only) exposure and risk 
assessments were conducted using the Dietary Exposure Evaluation Model 
(DEEM-FCID \TM\), Version 2.03. The dietary assessments assumed that 
100% of crops with the requested uses of ethiprole were treated and 
that all treated crops contained residues at tolerance-level residues 
for acute and chronic dietary exposure. In addition, empirical 
processing factors were assumed for the requested crop uses. EPA 
assessed dietary exposures from ethiprole in food as follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure. An unrefined, acute dietary 
exposure assessment using tolerance-level residues, empirical 
processing factors and assuming 100 percent crop treated (PCT) for the 
proposed commodities was conducted for the general U.S. population and 
various population subgroups.
    ii. Chronic exposure. An unrefined chronic dietary risk analysis 
was conducted with the DEEM-FCID \TM\ model, assuming tolerance-level 
residues, empirical processing factors, and 100 PCT.
    iii. Cancer. EPA determines whether quantitative cancer exposure 
and risk assessments are appropriate for a food-use pesticide based on 
the weight of the evidence from cancer studies and other relevant data. 
If quantitative cancer risk assessment is appropriate, cancer risk may 
be quantified using a linear or nonlinear approach. If sufficient 
information on the carcinogenic mode of action is available, a 
threshold or non-linear approach is used and a cancer RfD is calculated 
based on an earlier non-cancer key event. If carcinogenic mode of 
action data is not available, or if the mode of action data determines 
a mutagenic mode of action, a default linear cancer slope factor 
approach is utilized. Based on the data summarized in Unit III.A., EPA 
has determined that the cPAD will adequately account for all chronic 
effects, including carcinogenicity, likely to result from exposure to 
ethiprole. No separate exposure assessment pertaining to cancer risk 
was performed for ethiprole; rather, EPA relied on the chronic exposure 
assessment described in this Unit for assessing the risk of all chronic 
effects, including cancer.
    iv. Anticipated residue and PCT information. EPA did not use 
anticipated residue information in the dietary assessment for 
ethiprole. Tolerance-level residues and 100 PCT were assumed for all 
proposed food commodities.
    More detailed information on the acute and chronic dietary (food 
only)

[[Page 18919]]

exposure and risk assessment for ethiprole can be found in the document 
entitled, ``Ethiprole: Acute and Chronic Dietary (Food Only) Exposure 
and Risk Assessment for Proposed Imported Tolerances on Rice and Tea,'' 
dated December 1, 2010, by going to http://www.regulations.gov. The 
referenced document is available in the docket established by this 
action, which is described under ADDRESSES. Locate and click on the 
hyperlink for docket ID number EPA-HQ-OPP-2009-0493. Double-click on 
the document to view the referenced information on pages 6-8 of 12.
    2. Dietary exposure from drinking water. Ethiprole and its 
degradates were not considered for drinking water assessment because 
ethiprole is not registered for use in the U.S.; therefore, exposure to 
drinking water is precluded.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets). Ethiprole is not 
registered for any specific use patterns that would result in 
residential exposure.
    Further information regarding EPA standard assumptions and generic 
inputs for residential exposures may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when 
considering whether to establish, modify or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    Unlike other pesticides for which EPA has followed a cumulative 
risk approach based on a common mechanism of toxicity, EPA has not made 
a common mechanism of toxicity finding as to ethiprole and any other 
substances, and ethiprole does not appear to produce a toxic metabolite 
produced by other substances. For the purposes of this tolerance 
action; therefore, EPA has not assumed that ethiprole has a common 
mechanism of toxicity with other substances. For information regarding 
EPA's efforts to determine which chemicals have a common mechanism of 
toxicity, and to evaluate the cumulative effects of such chemicals, see 
the policy statements released by EPA's Office of Pesticide Programs 
concerning common mechanism determinations and procedures for 
cumulating effects from substances found to have a common mechanism on 
EPA's Web site at http://www.epa.gov/pesticides/cumulative/.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional ten-fold (10x) margin of safety for infants 
and children in the case of threshold effects to account for prenatal 
and postnatal toxicity, and the completeness of the database on 
toxicity and exposure unless EPA determines, based on reliable data, 
that a different margin of safety will be safer for infants and 
children. This additional margin of safety is commonly referred to as 
the FQPA SF. In applying this provision, EPA either retains the default 
value of 10x, or uses a different additional safety factor when 
reliable data are available to EPA to support the choice of a different 
factor.
    2. Prenatal and postnatal sensitivity. Although no teratogenic 
effects were observed in the existing toxicology database, there is 
uncertainty regarding the potential impact of ethiprole on thyroid 
hormone homeostasis in the developing organism. Given the observations 
that thyroid hormones were affected in several studies throughout the 
ethiprole database and the critical role thyroid hormones play in the 
development of the nervous system, the Agency is requiring a 
developmental thyroid toxicity study to assess for more subtle effects 
that may not be identified in the available core guideline studies.
    3. Conclusion. Based on the hazard and exposure data, the Agency is 
retaining the 10x FQPA SF due to the lack of a developmental thyroid 
toxicity study in rats. As described previously, hormonal changes 
(decreased T4 plasma levels, increased TSH plasma levels and alteration 
in thyroid weights) were observed in several studies following oral 
administration of ethiprole. Therefore, there is concern that 
perturbation of thyroid homeostasis may lead to hypothyroidism, and 
possibly result in adverse effects on the developing nervous system. 
Since the developmental and reproductive studies do not assess the 
thyroid in the developing animals, EPA has required that a 
developmental thyroid assay be conducted to evaluate the impact of 
ethiprole on thyroid hormones, structure and/or thyroid hormone 
homeostasis during development. EPA's determination on the FQPA SF is 
based on the following:
    i. The toxicological database for ethiprole is complete with the 
exception of a developmental thyroid toxicity study in juvenile rats, 
which is needed to address potential prenatal and perinatal thyroid 
toxicity. Thyroid toxicity was noted throughout the toxicological 
database; however, the thyroid toxicity was assessed in adult animals 
only.
    ii. In mammals, no neurotoxic effects were observed during the 
subchronic neurotoxicity study in which adverse effects of increased 
thyroid and liver weights were observed at 7.2/33 mg/kg/day (LOAEL) in 
males and females, respectively. The acute neurotoxicity study yielded 
a LOAEL of 250 mg/kg/day for decreased locomotor activity (both sexes, 
day 1) and FOB findings in both sexes on the day of treatment (4 hours 
after dosing). The FOB findings include increased tremors (females), 
decreased grooming (both sexes), decreased arousal alert (females), 
increased number of animals for which no assessment of gait was 
possible (females), increased eye closure (females), increased 
standing/sitting hunched (females), decreased activity and rearing 
counts (females), increased hindlimb and forelimb grip strength 
(males), decreased forelimb grip strength (day 8) (females), decreased 
splay (females, day 1), and increased splay (males, day 8). The 
similarity in the NOAELs from the acute neurotoxicity and subchronic 
neurotoxicity studies are consistent with the metabolism data that 
suggests that ethiprole is not accumulated in the system.
    A developmental neurotoxicity (DNT) study is not required for 
ethiprole. In view of the fact that thyroid toxicity appears to be the 
most sensitive endpoint, and thyroid hormones play a critical role in 
the development of the nervous system, the Agency is requiring the 
developmental thyroid toxicity study in lieu of the DNT.
    iii. There is no evidence that ethiprole results in increased 
susceptibility in in utero rats or rabbits in the prenatal 
developmental studies, or in young rats in the 2-generation 
reproduction study.
    iv. There are no residual uncertainties in the exposure database 
for ethiprole. Since the dietary exposure estimates were based on 
several conservative assumptions, the Agency does not believe that the 
exposure estimates are underestimated.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
aPAD and cPAD. For linear cancer risks, EPA calculates the

[[Page 18920]]

lifetime probability of acquiring cancer given the estimated aggregate 
exposure. Short-, intermediate-, and chronic-term risks are evaluated 
by comparing the estimated aggregate food, water, and residential 
exposure to the appropriate PODs to ensure that an adequate MOE exists. 
For this action, there is potential exposure to ethiprole from food 
only.
    1. Acute risk. An acute aggregate risk assessment takes into 
account acute exposure estimates from dietary consumption of food and 
drinking water. Using the exposure assumptions described in this unit 
for dietary and non-dietary acute exposures, EPA has concluded that 
acute exposure to ethiprole from food only will utilize 4% of the aPAD 
for the general U.S. population and 14% of the aPAD for all infants (<1 
year old), the population group receiving the greatest exposure. There 
are no residential uses for ethiprole. Based on the explanation in Unit 
III.C.3., regarding residential use patterns, acute residential 
exposure to residues of ethiprole is not expected.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
ethiprole from food only will utilize 22% of the cPAD for the general 
U.S. population and 42% of the cPAD for all infants (<1 year old), the 
population group receiving the greatest exposure. There are no 
residential uses for ethiprole. Based on the explanation in Unit 
III.C.3., regarding residential use patterns, chronic residential 
exposure to residues of ethiprole is not expected.
    3. Aggregate cancer risk for U.S. population. Based on the data 
summarized and referenced in Unit III.A., EPA has concluded that the 
cRfD/cPAD for ethiprole is protective of the cancer effects. As noted 
in this Unit, the chronic exposure for the general U.S. population 
utilizes 22% of the cPAD.
    4. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general U.S. population, or to infants and children, from 
aggregate exposure to ethiprole residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    The submitted data are adequate to satisfy residue analytical 
methods data requirements for tolerance enforcement purposes. The 
proposed High Performance Liquid Chromatography/Multistage Mass 
Spectrometer (HPLC/MS-MS) enforcement method, Method 01128, is 
acceptable for determination of residues of ethiprole and its sulfone 
metabolite RPA097973 for data collection in plant commodities. The 
proposed Gas Chromatograph-Electron Capture Device (GC-ECD) method 
(Report No. B003572) is suitable for determining residues of parent 
ethiprole and its sulfone metabolite RPA097973 in milk, eggs and 
tissues. The FDA multiresidue method testing study for ethiprole and 
its sulfone metabolite RPA097973 is adequate and indicates that PAM 
multiresidue methods are not suitable for enforcing maximum residue 
limits (MRLs) due to the thermolability of ethiprole.
    The method may be requested from: Chief, Analytical Chemistry 
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 
20755-5350; telephone number: (410) 305-2905; e-mail address: 
residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international MRLs established by the Codex Alimentarius 
Commission (Codex), as required by section 408(b)(4) of FFDCA. The 
Codex Alimentarius is a joint U.N. Food and Agriculture Organization/
World Health Organization food standards program, and it is recognized 
as an international food safety standards-setting organization in trade 
agreements to which the United States is a party. EPA may establish a 
tolerance that is different from a Codex MRL; however, section 
408(b)(4) of FFDCA requires that EPA explain the reasons for departing 
from the Codex level.
    There are currently no MRLs established by Codex for ethiprole. The 
tolerances established in this rule are identical to those being 
established in Canada.

C. Revisions to Petitioned-for Tolerances

    There are currently no U.S. tolerances or MRLs in Canada for 
ethiprole and no uses for ethiprole are currently being proposed in the 
U.S. or Canada. As part of PP 9E7550, Bayer CropScience LP proposed 
harmonized tolerances/MRLs for ethiprole residues to allow for the 
importation of ethiprole-treated rice (3.0 ppm) and tea (50 ppm) into 
the U.S. and Canada. In addition, Bayer CropScience LP proposed 
tolerances for the combined residues of the insecticide ethiprole in or 
on various livestock commodities.
    Adequate residue data are available from the rice field trials 
conducted in China, India and Thailand reflecting the critical use 
pattern for ethiprole on imported rice. The Agency's Guidance for 
Setting Pesticide Tolerances Based on Field Trial Data was utilized for 
determining appropriate tolerance level for ethiprole residues in or on 
rice, grain. EPA has determined that these residue data indicate that 
the tolerance in or on rice, grain should be set at 1.7 ppm.
    Adequate residue data are available from the tea field trials 
conducted in China reflecting the critical use pattern for ethiprole on 
imported tea. These residue data show that the highest average residues 
on plucked fresh tea leaves will be 11 ppm. Taking into account data 
from the tea processing study that shows that combined ethiprole 
residues concentrate by up to 2.53x in dried tea (green and black), EPA 
determined that a tolerance of 30 ppm for dried tea would be 
appropriate.
    EPA and PMRA are recommending the same tolerance values for rice 
and tea. In addition, EPA and PMRA are not establishing tolerances on 
livestock commodities since ethiprole is not registered in the U.S., 
and feedstuffs derived from rice are unlikely to be imported into the 
U.S. and Canada and fed to livestock. Further, based upon review of the 
available residue data supporting PP 9E7550, EPA has determined that 
the residue of concern in plant commodities (rice and tea) for both 
tolerance expression and risk assessment is only ethiprole.

V. Conclusion

    Therefore, permanent tolerances (without U.S. registrations) are 
being established for residues of the insecticide ethiprole, including 
its metabolites and degradate, in or on the imported plant commodities 
listed in this Unit. Compliance with the tolerance levels specified in 
this Unit is to be determined by measuring only ethiprole [5-amino-1-
[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(ethyl)-sulfinyl]-1H-
pyrazole-3-carbonitrile], in or on the following imported plant 
commodities: Rice, grain at 1.7 ppm; and tea, dried at 30 ppm.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this final rule has been 
exempted from review under Executive Order 12866, this final rule is

[[Page 18921]]

not subject to Executive Order 13211, entitled Actions Concerning 
Regulations That Significantly Affect Energy Supply, Distribution, or 
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled 
Protection of Children from Environmental Health Risks and Safety Risks 
(62 FR 19885, April 23, 1997). This final rule does not contain any 
information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any 
special considerations under Executive Order 12898, entitled Federal 
Actions to Address Environmental Justice in Minority Populations and 
Low-Income Populations (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under section 408(d) of FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply.
    This final rule directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled Federalism (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 9, 2000) do not apply to this final rule. In addition, 
this final rule does not impose any enforceable duty or contain any 
unfunded mandate as described under Title II of the Unfunded Mandates 
Reform Act of 1995 (UMRA) (Pub. L. 104-4).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 
note).

VII. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report to each House of the Congress and to 
the Comptroller General of the United States. EPA will submit a report 
containing this rule and other required information to the U.S. Senate, 
the U.S. House of Representatives, and the Comptroller General of the 
United States prior to publication of this final rule in the Federal 
Register. This final rule is not a ``major rule'' as defined by 5 
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

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

    Dated: March 25, 2011.
Steven Bradbury,
Director, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority: 21 U.S.C. 321(q), 346a and 371.


0
2. Section 180.652 is added to read as follows:


Sec.  180.652  Ethiprole; tolerances for residues.

    (a) General. Tolerances (without U.S. registrations) are 
established for residues of the insecticide ethiprole, including its 
metabolites and degradate, in or on the following commodities listed in 
the table. Compliance with the tolerance levels specified in the table 
is to be determined by measuring only ethiprole [5-amino-1-[2,6-
dichloro-4-(trifluoromethyl)phenyl]-4-[(ethyl)-sulfinyl]-1H-pyrazole-3-
carbonitrile], in or on the following commodities:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Rice, grain \1\...........................................           1.7
Tea, dried \1\............................................          30
------------------------------------------------------------------------
\1\ There are no U.S. registrations for rice and tea.

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 2011-8024 Filed 4-5-11; 8:45 am]
BILLING CODE 6560-50-P


