
[Federal Register: April 8, 2009 (Volume 74, Number 66)]
[Rules and Regulations]               
[Page 15869-15876]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08ap09-13]                         

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2008-0167; FRL-8407-8]

 
Thiamethoxam; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for combined residues 
of thiamethoxam and its metabolite CGA-322704 in or on citrus fruits, 
citrus pulp, tree nuts, almond hulls, and pistachios. Syngenta Crop 
Protection, Inc., requested these tolerances under the Federal Food, 
Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective April 8, 2009. Objections and 
requests for hearings must be received on or before June 8, 2009, 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-2008-0167. 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: Julie Chao, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8735; e-mail address: chao.julie@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 Access Electronic Copies of this Document?

    In addition to accessing electronically available documents at 
http://www.regulations.gov, you may access this Federal Register 
document electronically through the EPA Internet

[[Page 15870]]

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 e-CFR cite at http://www.gpoaccess.gov/ecfr.

C. 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 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-2008-0167 in the subject line on the first 
page of your submission. All requests must be in writing, and must be 
mailed or delivered to the Hearing Clerk as required by 40 CFR part 178 
on or before June 8, 2009.
    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 that is described in ADDRESSES. Information not marked 
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA 
without prior notice. Submit this copy, identified by docket ID number 
EPA-HQ-OPP-2008-0167, 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., N.W., 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. Petition for Tolerance

    In the Federal Register of April 16, 2008 (73 FR 20632) (FRL-8359-
1), 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 
7F7293) by Syngenta Crop Protection, Inc., P.O. Box 18300, Greensboro, 
NC 27419-8300. The petition requested that 40 CFR 180.565 be amended by 
establishing tolerances for combined residues of the insecticide 
thiamethoxam [3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-
nitro-4H-1,3,5-oxadiazin-4-imine] and its metabolite CGA-322704 [N-(2-
chloro-thiazol-5-ylmethyl)-N'-methyl-N'-nitro-guanidine], in or on 
fruit, citrus (crop group 10) at 0.3 parts per million (ppm); almond, 
nut, tree (crop group 14) including pistachio at 0.02 ppm; and almond 
hulls at 1.2 ppm. That notice referenced a summary of the petition 
prepared by Syngenta Crop Protection, Inc., the registrant, which is 
available to the public 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 
determined that the tolerance level for citrus (crop group 10) needs to 
be raised, and that separate tolerances need to be established for 
pistachios and citrus, dried pulp. 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 the petitioned-for 
tolerances for combined residues of thiamethoxam and its metabolite 
CGA-322704 on nut, tree (crop group 14) at 0.02 ppm; almond, hulls at 
1.2 ppm; fruit, citrus (crop group 10) at 0.40 ppm; citrus, dried pulp 
at 0.60 ppm; pistachio at 0.02 ppm. EPA's assessment of exposures and 
risks associated with establishing tolerances 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.
    Thiamethoxam shows toxicological effects primarily in the liver, 
kidney, testes, and hematopoietic system. In addition, developmental 
neurological effects were observed in rats. This developmental effect 
is being used to assess risks associated with acute exposures to 
thiamethoxam, and the liver and testicular effects are the bases for 
assessing longer term exposures. Although thiamethoxam causes liver 
tumors in mice, the Agency has classified thiamethoxam as ``not likely 
to be carcinogenic to humans'' based on convincing evidence that a non-
genotoxic mode of action for liver tumors was established in the mouse 
and that the carcinogenic effects are a result of a mode of action 
dependent on sufficient amounts of a hepatotoxic metabolite produced 
persistently. The non-cancer (chronic) assessment is sufficiently 
protective of the key events (perturbation of liver metabolism, 
hepatotoxicity/regenerative proliferation) in the animal mode of action 
for cancer published in the Federal Register of June 22, 2007 (72 FR 
34401 (FRL-8133-6). Thiamethoxam produces a metabolite known as CGA-
322704 (referred to in the remainder of this rule as clothianidin). 
Clothianidin is also registered as a pesticide. While some of the toxic 
effects observed following testing with the thiamethoxam and 
clothianidin are similar, the available information indicates that 
thiamethoxam and clothianidin have different toxicological effects in 
mammals and should be assessed separately. A separate risk assessment 
of clothianidin has been completed in conjunction with the registration 
of clothianidin. The most recent assessment, which provides details 
regarding the toxicology of clothianidin are discussed in the final 
rule published in the Federal Register of February 6, 2008 (FRL-8346-9) 
at (http://www.epa.gov/fedrgstr/EPA-

[[Page 15871]]

PEST/2008/February/Day-06/p1784.htm).
    Specific information on the studies received and the nature of the 
adverse effects caused by thiamethoxam as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies are discussed in the final rule 
published in the Federal Register of June 22, 2007.

B. Toxicological Endpoints

    For hazards that have a threshold below which there is no 
appreciable risk, a toxicological point of departure (POD) is 
identified as the basis for derivation of reference values for risk 
assessment. The POD may be defined as the highest dose at which no 
adverse effects are observed (the NOAEL) in the toxicology study 
identified as appropriate for use in risk assessment. However, if a 
NOAEL cannot be determined, the lowest dose at which adverse effects of 
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach 
is sometimes used for risk assessment. Uncertainty/safety factors (UFs) 
are used in conjunction with the POD to take into account uncertainties 
inherent in the extrapolation from laboratory animal data to humans and 
in the variations in sensitivity among members of the human population 
as well as other unknowns. Safety is assessed for acute and chronic 
dietary risks by comparing aggregate food and water exposure to the 
pesticide to the acute population adjusted dose (aPAD) and chronic 
population adjusted dose (cPAD). The aPAD and cPAD are calculated by 
dividing the POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and 
residential exposure to the POD to ensure that the margin of exposure 
(MOE) called for by the product of all applicable UFs is not exceeded. 
This latter value is referred to as the level of concern (LOC).
    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 
greater than that 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.
    A summary of the toxicological endpoints for thiamethoxam used for 
human risk assessment is discussed in Unit III.B. of the final rule 
published in the Federal Register of June 22, 2007.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to thiamethoxam, EPA considered exposure under the petitioned-
for tolerances as well as all existing thiamethoxam tolerances in (40 
CFR 180.565). EPA assessed dietary exposures from thiamethoxam in food 
as follows:
    For both acute and chronic exposure assessments for thiamethoxam, 
EPA combined residues of clothianidin coming from thiamethoxam with 
residues of thiamethoxam per se. As discussed in this unit, 
thiamethoxam's major metabolite is CGA-322704, which is also the 
registered active ingredient clothianidin. Available information 
indicates that thiamethoxam and clothianidin have different 
toxicological effects in mammals and should be assessed separately, 
however, these exposure assessments for this action incorporated the 
total residue of thiamethoxam and clothianidin from use of thiamethoxam 
because the total residue for each commodity for which thiamethoxam has 
a tolerance has not been separated between thiamethoxam and its 
clothianidin metabolite. The combining of these residues, as was done 
in this assessment, results in highly conservative estimates of dietary 
exposure and risk. A separate assessment was done for clothianidin. The 
clothianidin assessment included clothianidin residues from use of 
clothianidin as a pesticide and clothianidin residues from use of 
thiamethoxam on those commodities for which the pesticide clothianidin 
does not have a tolerance. As to these commodities, EPA has separated 
total residues between thiamethoxam and clothianidin.
    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.
    In estimating acute dietary exposure, EPA used food consumption 
information from the United States Department of Agriculture (USDA) 
1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by 
Individuals (CSFII). As to residue levels in food, EPA assumed maximum 
residues of thiamethoxam and clothianidin observed in the thiamethoxam 
field trials. It was also assumed that 100% of crops with registered or 
requested uses of thiamethoxam and 100% of crops with registered or 
requested uses of clothianidin are treated.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment, EPA used the food consumption data from the USDA 1994-1996 
and 1998 CSFII. As to residue levels in food, EPA assumed maximum 
residues of thiamethoxam and clothianidin observed in the thiamethoxam 
field trials. It was also assumed that 100% of crops with registered or 
requested uses of thiamethoxam and 100% of crops with registered or 
requested uses of clothianidin are treated.
    A complete listing of the inputs used in these assessments can be 
found in the following documents: Thiamethoxam Acute and Chronic 
Aggregate Dietary and Drinking Water Exposure and Risk Assessments for 
FIFRA Section 3 Registration on Citrus and Tree Nut Crops; 
Clothianidin. Acute and Chronic Aggregate Dietary (Food and Drinking 
Water) Exposure and Risk Assessments for the Section 3 Registration of 
Thiamethoxam on Citrus and Tree Nut Crop Groups. These documents are 
available in the docket EPA-HQ-OPP-2008-0167, at http:///
www.regulations.gov.
    iii. Cancer. A quantitative cancer exposure assessment is not 
necessary because EPA concluded that thiamethoxam is ``not likely to be 
carcinogenic to humans'' based on convincing evidence that a non-
genotoxic mode of action for liver tumors was established in the mouse, 
and that the carcinogenic effects are a result of a mode of action 
dependent on sufficient amounts of a hepatotoxic metabolite produced 
persistently. The non-cancer (chronic) assessment is sufficiently 
protective of the key events (perturbation of liver metabolism, 
hepatotoxicity/regenerative proliferation) in the animal mode of action 
for cancer and thus a separate exposure assessment pertaining to cancer 
risk is not necessary. Because clothianidin is not expected to pose a 
cancer risk, a quantitative dietary exposure assessment for the 
purposes of assessing cancer risk was not conducted.
    iv. Anticipated residue information. EPA did not use percent crop 
treated (PCT) information in the dietary assessments for thiamethoxam 
or clothianidin. Maximum field trial residues and 100 PCT were assumed 
for all food commodities.
    Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data 
and information on the anticipated residue levels of pesticide residues 
in food and the actual levels of pesticide residues

[[Page 15872]]

that have been measured in food. If EPA relies on such information, EPA 
must require pursuant to section 408(f)(1) of FFDCA that data be 
provided 5 years after the tolerance is established, modified, or left 
in effect, demonstrating that the levels in food are not above the 
levels anticipated. For the present action, EPA will issue such data 
Call-Ins as are required by section 408(b)(2)(E) of FFDCA and 
authorized under section 408(f)(1) of FFDCA. Data will be required to 
be submitted no later than 5 years from the date of issuance of these 
tolerances.
    2. Dietary exposure from drinking water. Thiamethoxam is expected 
to be persistent and mobile in terrestrial and aquatic environments. 
These fate properties suggest that thiamethoxam has a potential to move 
into surface water and shallow ground water. The Agency lacks 
sufficient monitoring data to complete a comprehensive dietary exposure 
analysis and risk assessment for thiamethoxam in drinking water. 
Because the Agency does not have comprehensive monitoring data, the 
Agency used screening level water exposure models in the dietary 
exposure analysis and risk assessment for thiamethoxam in drinking 
water. These simulation models take into account data on the physical, 
chemical, and fate/transport characteristics of thiamethoxam. Further 
information regarding EPA drinking water models used in pesticide 
exposure assessment can be found at http://www.epa.gov/oppefed1/models/
water/index.htm.
    Based on the Pesticide Root Zone Model/Exposure Analysis Modeling 
System (PRZM/EXAMS) and Screening Concentration in Groundwater (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of 
thiamethoxam for acute exposures are 12.26 parts per billion (ppb) for 
surface water and 7.94 ppb for ground water. The EDWCs for chronic 
exposures for non-cancer assessments are 1.29 ppb for surface water and 
7.94 ppb for ground water.
    The registrant has conducted small-scale prospective ground water 
studies in several locations in the United States to investigate the 
mobility of thiamethoxam in a vulnerable hydrogeological setting. A 
review of those data shows that generally residues of thiamethoxam, as 
well as CGA-322704, are below the limit of quantification (0.05 ppb). 
When quantifiable residues are found, they are sporadic and at low 
levels. The maximum observed residue levels from any monitoring well 
were 1.0 ppb for thiamethoxam and 0.73 ppb for CGA-322704. These values 
are well below the modeled estimates summarized in this unit, 
indicating that the modeled estimates are, in fact, protective of what 
actual exposures are likely to be.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For both acute and chronic 
dietary risk assessments for thiamethoxam, the upper-bound EDWC value 
of 12.26 ppb was used to assess the contribution to drinking water.
    Clothianidin is not a significant degradate of thiamethoxam in 
surface or ground water sources of drinking water. Clothianidin 
drinking water residues only result from uses of clothianidin. The 
acute EDWC value of 7.3 ppb for clothianidin was incorporated into the 
acute dietary assessment and the chronic EDWC value of 5.9 ppb for 
clothianidin was incorporated into the chronic dietary assessment.
    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).
    Thiamethoxam is currently registered for the following uses that 
could result in residential exposures: Turfgrass on golf courses, 
residential lawns, commercial grounds, parks, playgrounds, athletic 
fields, landscapes, interiorscapes and sod farms. EPA assessed 
residential exposure using the following assumptions:
    Thiamethoxam is registered for use on turfgrass on golf courses, 
residential lawns, commercial grounds, parks, playgrounds, athletic 
fields, landscapes, interiorscapes and sod farms. Thiamethoxam is 
applied by commercial applicators only. Therefore, exposures resulting 
from homeowner applications were not assessed. However, entering areas 
previously treated with thiamethoxam could lead to exposures for adults 
and children. As a result, risk assessments have been completed for 
postapplication scenarios. Short-term exposures (1 to 30 days of 
continuous exposure) may occur as a result of activities on treated 
turf. There are no use patterns for thiamethoxam that indicate 
intermediate-term (1 to 6 months of continuous exposure) or chronic 
non-dietary exposures are likely to occur.
    Dermal exposures were assessed for adults and children. Oral non-
dietary ingestion exposures (i.e. soil ingestion, and hand-/object-to-
mouth) were assessed for children as well. Since all postapplication 
scenarios occur outdoors the potential for inhalation exposure is 
negligible and therefore does not require an inhalation exposure 
assessment. For purposes of this assessment, exposure from residential 
lawns is used to represent the worst case scenario for both dermal and 
oral postapplication exposure.
    Postapplication dermal exposure resulting from contact with treated 
turf was assessed using the EPA's Standard Operating Procedures for 
Residential Exposure and a chemical-specific turf transfer residue 
study.
    Thiamethoxam use on turf does not result in significant residues of 
clothianidin. In addition, clothianidin residential and aggregate risks 
are not of concern. Refer to the final rule published in the Federal 
Register of February 6, 2008 (http://www.epa.gov/fedrgstr/EPA-PEST/
2008/February/Day-06/p1784.htm).
    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.''
    Thiamethoxam is a member of the neonicotinoid class of pesticides 
and produces, as a metabolite, another neonicotinoid, clothianidin. 
Structural similarities or common effects do not constitute a common 
mechanism of toxicity. Evidence is needed to establish that the 
chemicals operate by the same, or essentially the same sequence of 
major biochemical events (EPA, 2002). Although clothianidin and 
thiamethoxam bind selectively to insect nicotinic acetylcholine 
receptors (nAChR), the specific binding site(s)/receptor(s) for 
clothianidin, thiamethoxam, and the other neonicotinoids are unknown at 
this time. Additionally, the commonality of the binding activity itself 
is uncertain, as preliminary evidence suggests that clothianidin 
operates by direct competitive inhibition, while thiamethoxam is a non-
competitive inhibitor. Furthermore, even if future research shows that 
neonicotinoids share a common binding activity to a specific site on 
insect nicotinic acetylcholine receptors, there is not necessarily a 
relationship between this pesticidal action and a mechanism of toxicity 
in mammals. Structural variations between the insect and mammalian 
nAChRs produce quantitative differences in the binding affinity of the 
neonicotinoids towards these receptors, which, in turn, confers the 
notably greater selective toxicity of

[[Page 15873]]

this class towards insects, including aphids and leafhoppers, compared 
to mammals. While the insecticidal action of the neonicotinoids is 
neurotoxic, the most sensitive regulatory endpoint for thiamethoxam is 
based on unrelated effects in mammals, including effects on the liver, 
kidney, testes, and hematopoietic system. Additionally, the most 
sensitive toxicological effect in mammals differs across the 
neonicotinoids (e.g., testicular tubular atrophy with thiamethoxam; 
mineralized particles in thyroid colloid with imidacloprid).
    Thus, EPA has not found thiamethoxam or clothianidin to share a 
common mechanism of toxicity with any other substances. For the 
purposes of this tolerance action, therefore, EPA has assumed that 
thiamethoxam and clothianidin do not have 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 EPA's website 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 tenfold (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 safe for infants and children. This 
additional margin of safety is commonly referred to as the FQPA safety 
factor (SF). In applying this provision, EPA either retains the default 
value of 10X, or uses a different additional safety factor when 
reliable data available to EPA support the choice of a different 
factor.
    2. Prenatal and postnatal sensitivity. In the developmental 
studies, there is no evidence of increased quantitative or qualitative 
susceptibility of rat or rabbit fetuses to in utero exposure to 
thiamethoxam. The developmental NOAELs are either higher than or equal 
to the maternal NOAELs. The toxicological effects in fetuses do not 
appear to be any more severe than those in the dams or does. In the rat 
developmental neurotoxicity study, there was no quantitative evidence 
of increased susceptibility.
    There is evidence of increased quantitative susceptibility for male 
pups in two 2-generation reproductive studies. In one study, there are 
no toxicological effects in the dams whereas for the pups, reduced 
bodyweights are observed at the highest dose level, starting on day 14 
of lactation. This contributes to an overall decrease in bodyweight 
gain during the entire lactation period. Additionally, reproductive 
effects in males appear in the F1 generation in the form of increased 
incidence and severity of testicular tubular atrophy. These data are 
considered to be evidence of increased quantitative susceptibility for 
male pups (increased incidence of testicular tubular atrophy at 1.8 
milligrams/kilogram/day (mg/kg/day) when compared to the parents 
(hyaline changes in renal tubules at 61 mg/kg/ day; NOAEL is 1.8 mg/kg/
day).
    In a more recent 2-generation reproduction study, the most 
sensitive effect was sperm abnormalities at 3 mg/kg/day (the NOAEL is 
1.2 mg/kg/day) in the F1 males. This study also indicates increased 
susceptibility for the offspring for this effect.
    Although there is evidence of increased quantitative susceptibility 
for male pups in both reproductive studies, NOAELs and LOAELs were 
established in these studies and the Agency selected the NOAEL for 
testicular effects in F1 pups as the basis for risk assessment. The 
Agency has confidence that the NOAEL selected for risk assessment is 
protective of the most sensitive effect (testicular effects) for the 
most sensitive subgroup (pups) observed in the toxicological database.
    Due to the finding of quantitative sensitivity in the reproduction 
studies, the EPA conducted a degree of concern analysis to assess the 
residual uncertainties for prenatal and/or postnatal susceptibility. 
The Agency concluded that there is low concern for an increased 
susceptibility in the young given:
    i. There was no increased sensitivity (qualitative or quantitative) 
in the rat developmental, rabbit developmental and rat developmental 
neurotoxicity studies;
    ii. There was a clear NOAEL identified for the effects in pups in 
the rat reproduction studies where sensitivity was seen; and
    iii. The Agency selected this NOAEL as the basis for risk 
assessment.
    3. Conclusion. EPA has determined that reliable data show the 
safety of infants and children would be adequately protected if the 
FQPA SF were reduced to 1X. That decision is based on the following 
findings:
    i. The toxicity database for thiamethoxam is largely complete, 
including acceptable/guideline developmental toxicity, 2-generation 
reproduction, and developmental neurotoxicity studies designed to 
detect adverse effects on the developing organism, which could result 
from the mechanism that may have produced the decreased alanine amino 
transferase levels.
    The registrant must submit, as a condition of registration, an 
immunotoxicity study. This study is now required under 40 CFR part 158. 
The available data for thiamethoxam show the potential for immunotoxic 
effects, which are described in more detail below:
    a. Subchronic Dog - Leukopenia. In the subchronic dog study, 
leukopenia (decreased white blood cells) was observed in females only, 
at the highest dose tested (HDT) of 50 mg/kg/day; the NOAEL for this 
effect was 34 mg/kg/day. The overall study NOAEL was 9.3 mg/kg/day in 
females (8.2 mg/kg/day in males) based on hematology and other clinical 
chemistry findings at the LOAEL of 34 mg/kg/day (32 mg/kg/day in 
males).
    b. Subchronic Mouse - Spleen weight changes. In the subchronic 
mouse study, decreased spleen weights were observed in females at 626 
mg/kg/day; the NOAEL for this effect was the next lowest dose of 231 
mg/kg/day. The overall study NOAEL was 1.4 mg/kg/day (males) based on 
increased hepatocyte hypertrophy observed at the LOAEL of 14.3 mg/kg/
day. The decreased absolute spleen weights were considered to be 
treatment related, but were not statistically significant at 626 mg/kg/
day or at the HDT of 1,163 mg/kg/day. Since spleen weights were not 
decreased relative to body weights, the absolute decreases may have 
been related to the decreases in body weight gain observed at higher 
doses.

Overall, the Agency has a low concern for the potential for 
immunotoxicity related to these effects for the following reasons:

     In general, the Agency does not consider alterations in 
hematology parameters alone to be a significant indication of potential 
immunotoxicity. In the case of thiamethoxam, high-dose females in the 
subchronic dog study had slight microcytic anemia as well as leukopenia 
characterized by reductions in neutrophils, lymphocytes and monocytes; 
the leukopenia was considered to be related to the anemic response to 
exposure. Further, endpoints and doses selected for risk assessment are 
protective of the observed effects on hematology.
     Spleen weight decreases, while considered treatment-
related, were associated with decreases in body

[[Page 15874]]

weight gain, and were not statistically significant. In addition, 
spleen weight changes occurred only at very high doses, more than 70 
times higher than the doses selected for risk assessment.
    Therefore, an additional 10x safety factor is not warranted at this 
time.
    ii. For the reasons discussed in Unit III.D.2., there is low 
concern for an increased susceptibility in the young.
    iii. Although there is evidence of neurotoxicity after acute 
exposure to thiamethoxam at doses of 500 mg/kg/day including drooped 
palpebral closure, decrease in rectal temperature and locomotor 
activity and increase in forelimb grip strength, no evidence of 
neuropathology was observed. These effects occurred at doses at least 
fourteen-fold and 416-fold higher than the doses used for the acute, 
and chronic risk assessments, respectively; thus, there is low concern 
for these effects since it is expected that the doses used for 
regulatory purposes would be protective of the effects noted at much 
higher doses.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on assumption that the maximum residues of thiamethoxam and 
clothianidin observed in the thiamethoxam field trials were remaining 
on crops. Although there is available information indicating that 
thiamethoxam and clothianidin have different toxicological effects in 
mammals and should be assessed separately, the residues of each have 
been combined in these assessments to ensure that the estimated 
exposures of thiamethoxam do not underestimate actual potential 
thiamethoxam exposures. An assumption of 100 PCT was made for all foods 
evaluated in the assessments. For both the acute and chronic 
assessments the acute EDWC of 12.26 ppb (0.0123 ppm) was used as a 
worst-case estimate of exposure via drinking water. Compared to the 
results from small-scale prospective ground water studies where the 
maximum observed residue levels from any monitoring well were 1.0 ppb 
for thiamethoxam and 0.73 ppb for CGA-322704, the modeled estimates are 
protective of what actual exposures are likely to be. Similarly 
conservative Residential SOPs as well as a chemical-specific turf 
transfer residue (TTR) study were used to assess post-application 
exposure to children and incidental oral exposure of toddlers. These 
assessments will not underestimate the exposure and risks posed by 
thiamethoxam.
    v. The FQPA safety factor for clothianidin has been retained as a 
10x UFDB for the lack of a developmental immunotoxicity study. Refer to 
the final rule published in the Federal Register of February 6, 2008 
(http://www.epa.gov/fedrgstr/EPA-PEST/2008/February/Day-06/p1784.htm).

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic pesticide exposures are 
safe by comparing aggregate exposure estimates to the aPAD and cPAD. 
The aPAD and cPAD represent the highest safe exposures, taking into 
account all appropriate SFs. EPA calculates the aPAD and cPAD by 
dividing the POD by all applicable UFs. For linear cancer risks, EPA 
calculates the probability of additional cancer cases 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 POD to ensure that the MOE called for 
by the product of all applicable UFs is not exceeded.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food and water 
to thiamethoxam will occupy 3% of the aPAD for children 1 to 2 years 
old, the population group receiving the greatest exposure. Acute 
dietary exposure from food and water to clothianidin is estimated to 
occupy 45% of the aPAD for children 1 to 2 years old, the population 
group receiving the greatest exposure.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
thiamethoxam from food and water will utilize 42% of the cPAD for 
children 1 to 2 years old, the population group receiving the greatest 
exposure. Similarly, chronic exposure to clothianidin from food and 
water will occupy 16% of the cPAD for children 1 to 2 years old. Based 
on the explanation in Unit III.C.3., regarding residential use 
patterns, chronic residential exposure to residues of thiamethoxam and 
clothianidin is not expected.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level).
    Thiamethoxam is currently registered for uses that could result in 
short-term residential exposure and the Agency has determined that it 
is appropriate to aggregate chronic food and water and short-term 
residential exposures for thiamethoxam. The level of concern for the 
margin of exposure (MOE) is 100 for aggregate short-term exposures 
(i.e., MOEs less than 100 indicate potential risks of concern). The 
level of concern for clothianidin MOEs is 1,000.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the aggregated short-term food, 
water, and residential exposures to thiamethoxam result in MOEs of 730 
through 2,800 for all exposure scenarios for infants, children and 
adults. Aggregate MOEs associated with clothianidin range from 1,100 to 
23,000.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level).
    Thiamethoxam is not registered for any use patterns that would 
result in intermediate-term residential exposure. Therefore, the 
intermediate-term aggregate risk is the sum of the risk from exposure 
to thiamethoxam or clothianidin through food and water, which has 
already been addressed, and will not be greater than the chronic 
aggregate risk.
    5. Aggregate cancer risk for U.S. population. The Agency has 
classified thiamethoxam as not likely to be a human carcinogen based on 
convincing evidence that a non-genotoxic mode of action for liver 
tumors was established in the mouse and that the carcinogenic effects 
are a result of a mode of action dependent on sufficient amounts of a 
hepatotoxic metabolite produced persistently. Thiamethoxam is not 
expected to pose a cancer risk. Clothianidin has been classified as a 
``not likely to be a human carcinogen.'' It is not expected to pose a 
cancer risk.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, or to infants and children from aggregate 
exposure to thiamethoxam or clothianidin residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (high-performance liquid 
chromatography/ultraviolet (HPLC/UV) or mass spectrometry (MS)) is 
available to enforce the tolerance expression. 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.

[[Page 15875]]

B. International Residue Limits

    There are no CODEX or Mexican maximum residue limits (MRLs) for 
thiamethoxam. A number of Canadian MRLs exist for this chemical and are 
in accord with U.S. tolerances. The new/revised tolerances established 
by this rule have been derived using the NAFTA Tolerance Harmonization 
Spreadsheet.

C. Revisions to Petitioned-For Tolerances

    Available field trial data support a tolerance for combined 
residues of thiamethoxam and CGA-322704 in/on citrus (group 10) at 0.40 
ppm. Therefore, the proposed tolerance of 0.30 ppm should be raised to 
0.40 ppm.
    The data submitted with the petition support the proposed tolerance 
of 0.02 ppm for tree nuts (group 14). However, because the petitioner 
is seeking a tolerance to cover use on pistachios and pistachios are 
not, pending a proposed revision of the tree nut group definition, 
included in the tree nut group, a separate tolerance should be 
established for pistachio at 0.02 ppm.
    The data supporting the petition indicate that combined residues of 
thiamethoxam and CGA-332704 may concentrate in dried citrus pulp. 
Therefore, a tolerance for citrus, dried pulp should be established and 
EPA has determined that the appropriate level is 0.60 ppm.

V. Conclusion

    Therefore, tolerances are established for combined residues of 
thiamethoxam, [3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-
nitro-4H-1,3,5-oxadiazin-4-imine], and its metabolite, CGA-322704 [N-
(2-chloro-thiazol-5-ylmethyl)-N'-methyl-N'-nitro-guanidine], in or on 
nut, tree (crop group 14) at 0.02 ppm; almond, hulls at 1.2 ppm; fruit, 
citrus (crop group 10) at 0.40 ppm; citrus, dried pulp at 0.60 ppm; 
pistachio at 0.02 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 
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) (Public Law 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 30, 2009.
Daniel J. Rosenblatt,
Acting Director, Registration Division, Office of Pesticide Programs.

0
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 180.565 is amended by revising the introductory text in 
paragraph (a); removing the commodity ``pecan'' from the table in 
paragraph (a); alphabetically adding the following commodities to the 
table; and removing paragraph (b) and reserving the heading to read as 
follows:


Sec.  180.565  Thiamethoxam; tolerances for residues.

    (a) General. A tolerance is established for the combined residues 
of the insecticide thiamethoxam [3-[(2-chloro-5-
thiazolyl)methyl]tetrahydro-5-methyl- N -nitro-4 H -1,3,5-oxadiazin-4-
imine] (CAS Reg. No. 153719-23-4) and its metabolite [N-(2-chloro-
thiazol-5-ylmethyl) -N '-methyl- N '-nitro-guanidine], calculated as 
parent equivalents, in or on the following raw agricultural 
commodities:

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
Almond, hulls........................................            1.2 ppm
                                * * * * *
Citrus, dried pulp...................................           0.60 ppm
                                * * * * *
Fruit, citrus, group 10..............................           0.40 ppm
                                * * * * *
Nut, tree, group 14).................................           0.02 ppm
                                * * * * *
Pistachio............................................           0.02 ppm
                                * * * * *
------------------------------------------------------------------------

* * * * *

[[Page 15876]]

    (b) Section 18 emergency exemptions. [Reserved]
* * * * *

[FR Doc. E9-7966 Filed 4-7-09; 8:45 am]

BILLING CODE 6560-50-S
