[Federal Register Volume 75, Number 120 (Wednesday, June 23, 2010)]
[Rules and Regulations]
[Pages 35653-35660]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-15035]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2009-0737; FRL-8830-4]


Thiamethoxam; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
thiamethoxam in or on onion, dry bulb. Syngenta Crop Protection, Inc., 
requested these tolerances under the Federal Food, Drug, and Cosmetic 
Act (FFDCA).

DATES: This regulation is effective June 23, 2010. Objections and 
requests for hearings must be received on or before August 23, 2010, 
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-2009-0737. 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: [email protected].

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 FFDCA section 408(g), 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-2009-0737 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 
August 23, 2010. 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-2009-0737, 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

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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 January 6, 2010, (75 FR 864) (FRL-8801-
5), 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 
9F7582) by Syngenta Crop Protection, Inc., P.O. Box 18300, Greensboro, 
NC 27419. The petition requested that 40 CFR 180.565 be amended by 
establishing tolerances for 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 onion, dry bulb at 
0.03 parts per million (ppm). That notice referenced a summary of the 
petition prepared by Syngenta Crop Protection, Inc., the registrant, 
which is available in the docket EPA-HQ-OPP-2009-0737, at http://www.regulations.gov. There were no comments received in response to the 
notice of filing.

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 thiamethoxam including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with thiamethoxam 
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. Refer to the Federal Register of June 22, 2007 (72 FR 
34401) (FRL-8133-6) for more information regarding the cancer 
classification of thiamethoxam.
    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 assessments, which provide details regarding the toxicology 
of clothianidin, are available in the docket EPA-HQ-OPP-2008-0945, at 
http://www.regulations.gov. Refer to the documents ``Clothianidin: 
Human Health Risk Assessment for Proposed Uses on Berries (Group 13-
07H), Brassica Vegetables (Group 5), Cotton, Cucurbit Vegetables (Group 
9), Fig, Fruiting Vegetables (Group 8), Leafy Green Vegetables (Group 
4A), Peach, Pomegranate, Soybean, Tree Nuts (Group 14), and Tuberous 
and Corm Vegetables (Group 1C);'' and ``Clothianidin: Human Health Risk 
Assessment for Proposed Seed Treatment Uses on Root and Tuber 
Vegetables (Group 1), Bulb Vegetables (Group 3), Leafy Green Vegetables 
(Group 4A), Brassica Leafy Vegetables (Group 5), Fruiting Vegetables 
(Group 8), Cucurbit Vegetables (Group 9), and Cereal Grains (Group 15, 
except rice).''
    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 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 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 no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the 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.

[[Page 35655]]

    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.
    Such effects were identified for thiamethoxam. 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 tolerance-level residues of thiamethoxam 
and clothianidin. 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 tolerance 
level and/or anticipated residues from 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 (Food and Drinking Water) Exposure and Risk 
Assessments for the Section 3 Registration as a Seed Treatment on 
Onion, Dry Bulb, Removing the Geographical Limitations on the Foliar 
Treatment of Barley,'' available in the docket EPA-HQ-OPP-2009-0737, at 
http://www.regulations.gov; and ``Clothianidin Acute and Chronic 
Aggregate Dietary (Food and Drinking Water) Exposure and Risk 
Assessments,'' available in the docket EPA-HQ-OPP- 2008-0945, at http://www.regulations.gov.
    iii. Cancer. 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 and percent crop treated (PCT) information. 
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 that have been 
measured in food. If EPA relies on such information, EPA must require 
pursuant to FFDCA section 408(f)(1) 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 FFDCA section 408(b)(2)(E) and authorized under 
FFDCA section 408(f)(1). Data will be required to be submitted no later 
than 5 years from the date of issuance of these tolerances.
    EPA did not use PCT information in the dietary assessments for 
thiamethoxam or clothianidin.
    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.
    For surface water, the estimated drinking water concentrations 
(EDWCs) are based on thiamethoxam concentrations in tail water from 
rice paddies and cranberry bogs that drain into adjacent surface water 
bodies. Because the uses on rice and cranberries involve flooding, for 
which Pesticide Root Zone Model/Exposure/Analysis Modeling System 
(PRZM/EXAMS) is not currently parameterized, these uses were assessed 
using the modified Tier I Rice Model and the Provisional Cranberry 
Model. Exposure estimates were refined with a default percent cropped 
area factor of 87%. The Tier I Rice Model is expected to generate 
conservative EDWCs that exceed peak measured concentrations of 
pesticides in water bodies well downstream of rice paddies by less than 
one order of magnitude to multiple orders of magnitude.
    For ground water, the EDWCs are based on thiamethoxam 
concentrations resulting from use on grapes. Exposure in ground water 
due to leaching was assessed with the Screening

[[Page 35656]]

Concentration in Ground water (SCI-GROW) models.
    Based on the Tier I Rice Model and SCI-GROW models, the EDWCs of 
thiamethoxam for acute exposures are 131.77 parts per billion (ppb) for 
tail water and 4.14 ppb for ground water. The EDWCs for chronic 
exposures for non-cancer assessments are 11.31 ppb for tail water and 
4.14 ppb for ground water.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. The most conservative EDWCs in 
both the acute and chronic exposure scenarios were for tail water, and 
represent worst case scenarios. Therefore, for the acute dietary risk 
assessments for thiamethoxam, the upper-bound EDWC value of 131.77 ppb 
was used to assess the contribution to drinking water. For the chronic 
dietary risk assessments for thiamethoxam, the upper-bound EDWC value 
of 11.31 ppb was used to assess the contribution to drinking 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 show 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.
    Clothianidin is not a significant degradate of thiamethoxam in 
surface water or ground water sources of drinking water and, therefore, 
was not included in the EDWCs used in the thiamethoxam dietary 
assessments. For the clothianidin assessments, the acute EDWC value of 
7.29 ppb for clothianidin was incorporated into the acute dietary 
assessment and the chronic EDWC value of 5.88 ppb for clothianidin was 
incorporated into the chronic dietary assessment.
    A complete listing of the inputs used in these assessments can be 
found in the following documents ``Thiamethoxam. Acute and Chronic 
Aggregate Dietary (Food and Drinking Water) Exposure and Risk 
Assessments for the Section 3 Registration as a Seed Treatment on 
Onion, Dry Bulb, Removing the Geographical Limitations on the Foliar 
Treatment of Barley,'' available in the docket EPA-HQ-OPP-2009-0737, at 
http://www.regulations.gov; and ``Clothianidin Acute and Chronic 
Aggregate Dietary (Food and Drinking Water) Exposure and Risk 
Assessments,'' available in the docket EPA-HQ-OPP-2008-0945, at http://www.regulations.gov.
    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; indoor crack and 
crevice or spot treatments to control insects in residential settings. 
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) and for indoor use to 
control insects in residential settings. Thiamethoxam is applied by 
commercial applicators only. Therefore, exposures resulting to 
homeowners from applying thiamethoxam 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 post-application scenarios.
    Short-term exposures (1 to 30 days of continuous exposure) may 
occur as a result of activities on treated turf. Short-term and 
intermediate-term exposures (30 to 90 days of continuous exposure) may 
occur as a result of entering indoor areas previously treated with a 
thiamethoxam indoor crack and crevice product. The difference between 
short-term and intermediate-term aggregate risk is the frequency of 
hand-to-mouth events for children. For short-term exposure there are 20 
events per hour and for intermediate-term exposure there are 9.5 events 
per hour. The doses and end-points for short-term and intermediate-term 
aggregate risk are the same.
    EPA combined all non-dietary sources of post-application exposure 
to obtain an estimate of potential combined exposure. These scenarios 
consisted of adult and toddler dermal post-application exposure and 
oral (hand-to-mouth) exposures for toddlers. Since post-application 
scenarios for turf occur outdoors, the potential for inhalation 
exposure is negligible and therefore does not require an inhalation 
exposure assessment. Since thiamethoxam has a very low vapor pressure 
(6.6 x 10-9 Pa @ 25[deg]C), inhalation exposure is also expected to be 
negligible as a result of indoor crack and crevice use. Therefore, a 
quantitative post-application inhalation exposure assessment was not 
performed.
    A complete listing of the inputs used in these assessments can be 
found in the following documents ``Thiamethoxam: Occupational and 
Residential Exposure/Risk Assessment for Proposed Section 3 
Registration for Seed Treatment Use on Bulb Onions,'' available in the 
docket EPA-HQ-OPP-2009-0737, at http://www.regulations.gov.
    Thiamethoxam use on turf or as an indoor crack and crevice or spot 
treatment does not result in significant residues of clothianidin. In 
addition, clothianidin residential and aggregate risks are not of 
concern. For further details, refer to the documents ''Clothianidin: 
Human Health Risk Assessment for Proposed Uses on Berries (Group 13-
07H), Brassica Vegetables (Group 5), Cotton, Cucurbit Vegetables (Group 
9), Fig, Fruiting Vegetables (Group 8), Leafy Green Vegetables (Group 
4A), Peach, Pomegranate, Soybean, Tree Nuts (Group 14), and Tuberous 
and Corm Vegetables (Group 1C);'' and ``Clothianidin: Human Health Risk 
Assessment for Proposed Seed Treatment Uses on Root and Tuber 
Vegetables (Group 1), Bulb Vegetables (Group 3), Leafy Green Vegetables 
(Group 4A), Brassica Leafy Vegetables (Group 5), Fruiting Vegetables 
(Group 8), Cucurbit Vegetables (Group 9), and Cereal Grains (Group 15, 
except rice),'' available in the docket EPA-HQ-OPP-2008-0945, at http:/
//www.regulations.gov.
    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.''
    Thiamethoxam is a member of the neonicotinoid class of pesticides 
and produces, as a metabolite, another neonicotinoid, clothianidin. 
Structural

[[Page 35657]]

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 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 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.
    3. Conclusion. a. In the final rule published in the Federal 
Register of January 5, 2005 (70 FR 708) (FRL-7689-7), EPA had 
previously determined that the FQPA SF should be retained at 10X for 
thiamethoxam, based on the following factors: Effects on endocrine 
organs observed across species; significant decrease in alanine amino 
transferase levels in companion animal studies and in dog studies; the 
mode of action of this chemical in insects (interferes with the 
nicotinic acetylcholine receptors of the insect's nervous system); the 
transient clinical signs of neurotoxicity in several studies across 
species; and the suggestive evidence of increased quantitative 
susceptibility in the rat reproduction study.
    Since that determination, EPA has received and reviewed an 
developmental neurotoxicity (DNT) study in rats, and an additional 
reproduction study in rats. Taking the results of these studies into 
account, as well as the rest of the data on thiamethoxam, 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 DNT 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 now 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. 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). 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)

[[Page 35658]]

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 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 for 
thiamethoxam 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 using 
tolerance-level and/or anticipated residues that are based on reliable 
field trial data observed in the thiamethoxam field trials. 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 the acute and chronic assessments, the EDWCs of 
131.77 ppb and 11.3 ppb, respectively, were used to estimate 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 SOP, 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.
    b. In the final rule published in the Federal Register of February 
6, 2008 (73 FR 6851) (FRL-8346-9), EPA had previously determined that 
the FQPA SF for clothianidin should be retained at 10X because EPA had 
required the submission of a developmental immunotoxicity study to 
address the combination of evidence of decreased absolute and adjusted 
organ weights of the thymus and spleen in multiple studies in the 
clothianidin database, and evidence showing that juvenile rats in the 
2-generation reproduction study appear to be more susceptible to these 
potential immunotoxic effects. In the absence of a developmental 
immunotoxicity study, EPA concluded that there was sufficient 
uncertainty regarding immunotoxic effects in the young that the 10X 
FQPA factor should be retained as a database uncertainty factor.
    Since that determination, EPA has received and reviewed an 
acceptable/guideline developmental immunotoxicity study, which 
demonstrated no treatment-related effects. Taking the results of this 
study into account, as well as the rest of the data on clothianidin, 
EPA has determined that reliable data show the safety of infants and 
children would be adequately protected if the FQPA SF for clothianidin 
were reduced to 1X. That decision is based on the following findings:
    i. The toxicity database for clothianidin is complete. As noted, 
the prior data gap concerning developmental immunotoxicity has been 
addressed by the submission of an acceptable developmental 
immunotoxicity study.
    ii. A rat developmental neurotoxicity study is available and shows 
evidence of increased quantitative susceptibility of offspring. 
However, EPA considers the degree of concern for the developmental 
neurotoxicity study to be low for prenatal and postnatal toxicity 
because the NOAEL and LOAEL were well characterized, and the doses and 
endpoints selected for risk assessment are protective of the observed 
susceptibility; therefore, there are no residual concerns regarding 
effects in the young.
    iii. While the rat multi-generation reproduction study showed 
evidence of increased quantitative susceptibility of offspring compared 
to adults, the degree of concern is low because the study NOAEL and 
LOAEL have been selected for risk assessment purposes for relevant 
exposure routes and durations. In addition, the potential immunotoxic 
effects observed in the study have been further characterized with the 
submission of a developmental immunotoxicity study that showed no 
evidence of susceptibility. As a result, there are no concerns or 
residual uncertainties for prenatal and postnatal toxicity after 
establishing toxicity endpoints and traditional UFs to be used in the 
risk assessment for clothianidin.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on assumptions that were judged to be highly conservative and health-
protective for all durations and population subgroups, including 
tolerance-level residues, adjustment factors from metabolite data, 
empirical processing factors, and 100 PCT for all commodities. 
Additionally, EPA made conservative (protective) assumptions in the 
ground water and surface water modeling used to assess exposure to 
clothianidin in drinking water. EPA used similarly conservative 
assumptions to assess post-application exposure of children and adults 
as well as incidental oral exposure of toddlers. These assessments will 
not underestimate the exposure and risks posed by clothianidin.

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 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer

[[Page 35659]]

risks, EPA calculates the lifetime probability of acquiring cancer 
given the estimated aggregate exposure. Short-term, intermediate-term, 
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.
    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 9.5% 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 23% 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. Chronic exposure to clothianidin from food and water will 
utilize 19% of the cPAD for children 1 to 2 years old, the population 
group receiving the greatest exposure. 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 exposure through food and water 
with short-term residential exposures to thiamethoxam.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential exposures for thiamethoxam result in aggregate MOEs of: 
380 for the general U.S. population; 500 for all infants (<1 year); 440 
for children 1 to 2 years; 460 for children 3-5 years; 370 for children 
6-12 years; 380 for youth 13-19 years, adults 20-49 years, adults 50+ 
years, and females 13-49 years. Because EPA's level of concern for 
thiamethoxam is a MOE of 100 or below, these MOEs are not of concern.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential exposures for clothianidin result in aggregate MOEs of 
1,700 for the general U.S. population; 480 for all infants (<1 year); 
380 for children 1 to 2 years; 500 for children 3-5 years; 1,400 for 
children 6-12 years; 2,200 for youth 13-19 years, adults 20-49 years, 
and females 13-49 years; 2,100 for adults 50+ years. Because EPA's 
level of concern for clothianidin is a MOE of 100 or below, these MOEs 
are not of concern.
    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 currently registered for uses that could result in 
intermediate-term residential exposure, and the Agency has determined 
that it is appropriate to aggregate chronic exposure through food and 
water with intermediate-term residential exposures to thiamethoxam.
    Using the exposure assumptions described in this unit for 
intermediate-term exposures, EPA has concluded that the combined 
intermediate-term food, water, and residential exposures result in 
aggregate MOEs of 380 for the general U.S. population; 540 for all 
infants (<1 year); 480 for children 1 to 2 years; 500 for children 3-5 
years; 370 for children 6-12 years; 380 for youth 13-19 years, adults 
20-49 years, adults 50+ years, and females 13-49 years. Because EPA's 
level of concern for thiamethoxam is a MOE of 100 or below, these MOEs 
are not of concern.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential exposures for clothianidin result in aggregate MOEs of 
1,700 for the general U.S. population; 480 for all infants (<1 year); 
380 for children 1 to 2 years; 500 for children 3-5 years; 1,400 for 
children 6-12 years; 2,200 for youth 13-19 years, adults 20-49 years, 
and females 13-49 years; 2,100 for adults 50+ years. Because EPA's 
level of concern for clothianidin is a MOE of 100 or below, these MOEs 
are not of concern.
    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. Therefore, thiamethoxam 
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: 
[email protected].
    For further details, refer to the document ``Thiamethoxam. Petition 
to Establish a Permanent Tolerance for Residues of the Insecticide 
Resulting from Food/Feed Use as a Seed Treatment on Bulb Onions. 
Response to Data Gaps from Conditional Registration of Various Food/
Feed Crops (as Specified in HED Memo D281702; M. Doherty; 17 April 
2007). Summary of Analytical Chemistry and Residue Data,'' available in 
the docket EPA-HQ-OPP-2009-0737, at http://www.regulations.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 maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). 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, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level. The Codex has not 
established a MRL for thiamethoxam.

V. Conclusion

    Therefore, tolerances are established for residues of thiamethoxam 
(3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-

[[Page 35660]]

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 onion, dry bulb at 0.03 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: June 14, 2010.
Lois Rossi,
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 alphabetically adding the following 
commodity to the table in paragraph (a) to read as follows:


Sec.  180.565  Thiamethoxam; tolerances for residues.

    (a) * * *

----------------------------------------------------------------------------------------------------------------
                       Commodity                                            Parts per million
----------------------------------------------------------------------------------------------------------------
                                                    * * * * *
Onion, dry bulb.......................................                                                      0.03
                                                    * * * * *
----------------------------------------------------------------------------------------------------------------

* * * * *
[FR Doc. 2010-15035 Filed 6-22-10; 8:45 am]
BILLING CODE 6560-50-S