[Federal Register Volume 78, Number 59 (Wednesday, March 27, 2013)]
[Rules and Regulations]
[Pages 18511-18518]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-06759]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0488; FRL-9377-3]


Thiamethoxam; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for residues of the 
insecticide thiamethoxam in or on tea, and amends the existing 
tolerance for residues of thiamethoxam in or on coffee. Syngenta Crop 
Protection, Inc., requested these tolerances under the Federal Food, 
Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective March 27, 2013. Objections and 
requests for hearings must be received on or before May 28, 2013, 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: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2012-0488, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution 
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open 
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Public Reading Room is (202) 
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information 
about the docket available at http://www.epa.gov/dockets.

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; email 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. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

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 Web site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

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

[[Page 18512]]

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-2012-0488 in the subject line on the first 
Web 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 May 28, 2013. 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 (excluding any Confidential Business Information (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 the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2012-0488, by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.htm. Additional 
instructions on commenting or visiting the docket, along with more 
information about dockets generally, is available at http://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of August 22, 2012 (77 FR 50661) (FRL-9358-
9), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
2E8036) by Syngenta Crop Protection, Inc.; P.O. Box 18300; Greensboro, 
NC 27419. The petition requested that 40 CFR 180.565 be amended by 
increasing the tolerance for residues of the insecticide thiamethoxam, 
(3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4 H -
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 coffee from 
0.05 parts per million (ppm) to 0.2 ppm. That document referenced a 
summary of the petition prepared by Syngenta Crop Protection, Inc., the 
registrant, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the 
notice of filing.
    In the Federal Register of December 19, 2012 (77 FR 75082) (FRL-
9372-6), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
2E8011) by Syngenta Crop Protection, Inc.; P.O. Box 18300; Greensboro, 
NC 27419. The petition requested that 40 CFR 180.565 be amended by 
establishing a tolerance for residues of the insecticide thiamethoxam, 
(3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4 H-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 tea at 20 ppm. That 
document referenced a summary of the petition prepared by Syngenta Crop 
Protection, Inc., the registrant, which is available in the docket, 
http://www.regulations.gov. The notice of filing mistakenly referenced 
PP 2E8011. The correct petition number is PP 2E8100. 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 FFDCA section 408(b)(2)(D), and the factors 
specified in FFDCA section 408(b)(2)(D), 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 basis 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 in the mouse. 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.
    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 can be found at http://www.regulations.gov in Section 4.5.1 of the documents ``Thiamethoxam. 
Human Health Risk Assessment for the Higher Tolerance, Use of New 
Formulations, and Increased Maximum Seasonal Application Rate on 
Imported Coffee Beans, and Condition-of-Registration Data for Leafy 
Vegetables (Group 4),'' in docket ID number EPA-HQ-OPP-2012-0488, and 
``Thiamethoxam. Human Health Risk Assessment for Residues on

[[Page 18513]]

Imported Tea Leaves (Dried),'' in docket ID number EPA-HQ-OPP-2012-
0858.
    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 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, which takes 
into account contributions from thiamethoxam, has been completed in 
conjunction with the registration of clothianidin. The most recent 
assessment, which provides details regarding the toxicology of 
clothianidin, is available in the docket EPA-HQ-OPP-2011-0860, at 
http://www.regulations.gov. Refer to the document ``Clothianidin--
Aggregate Human Health Risk Assessment of New Uses on Strawberry, 
Pistachio, and Citrus; New Tolerance for Tea; and Revised PHI and 
Tolerance for Pepper and Eggplant (Crop Subgroup 8-10B).''

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.
    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 March 2, 2012 (77 FR 12731) (FRL-
9331-8).

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 the previous 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 or clothianidin residues from use of thiamethoxam on those 
commodities for which the pesticide clothianidin does not have a 
tolerance. The two sources of clothianidin were not combined for a 
given commodity because (1) residues of clothianidin are greater from 
clothianidin use than from thiamethoxam use; and (2) it was assumed 
that 100% of crops are treated.
    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 U.S. Department of Agriculture's 
National Health and Nutrition Examination Survey, What We Eat in 
America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to 
2008. As to residue levels in food, EPA assumed tolerance level 
residues of thiamethoxam and clothianidin. It was further assumed that 
100% of crops with registered or requested uses of thiamethoxam and 
100% of crops with registered or requested uses of clothianidin were 
treated.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment EPA used the food consumption data from the U.S. Department 
of Agriculture's National Health and Nutrition Examination Survey, What 
We Eat in America, (NHANES/WWEIA). This dietary survey was conducted 
from 2003 to 2008. As to residue levels in food, EPA assumed tolerance 
level and/or anticipated residues (averages) from field trial data. It 
was again assumed that 100% of crops with registered or requested uses 
of thiamethoxam and 100% of crops with registered or requested uses of 
clothianidin were 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 Use of Thiamethoxam on 
Imported Coffee Beans and Condition-of-Registration Residue Data for 
Leaf Lettuce,'' available in the docket EPA-HQ-OPP-2012-0488; 
``Thiamethoxam. Acute and Chronic Aggregate Dietary (Food and Drinking 
Water) Exposure and Risk Assessments for Residues of Thiamethoxam on 
Imported Tea,'' available in the docket EPA-HQ-OPP-2012-0858; and 
``Clothianidin--Aggregate Human Health Risk Assessment of New Uses on 
Strawberry, Pistachio, and Citrus; New Tolerance for Tea; and Revised 
PHI and Tolerance for Pepper and Eggplant (Crop Subgroup 8-10B),'' 
available in the docket EPA-HQ-OPP-2011-0860, 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 in the mouse. 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

[[Page 18514]]

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. 
Tolerance level residues or anticipated residues (average) from the 
field trial data were used for the chronic assessment for thiamethoxam. 
It was assumed that 100% of crops were treated for all food commodities 
in both the acute and chronic analyses.
    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.
    2. Dietary exposure from drinking water. 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 Tier 1 Rice Model for surface water and the Screening 
Concentration in Ground Water (SCI-GROW) model for ground water, the 
estimated drinking water concentrations (EDWCs) of thiamethoxam for 
acute exposures are estimated to be 0.13177 ppm for surface water and 
0.00466 ppm for ground water. The chronic concentrations for surface 
water and ground water are estimated to be 0.01131 ppm and 0.00466 ppm, 
respectively. Modeled estimates of drinking water concentrations were 
directly entered into the dietary exposure model. Since clothianidin is 
not a significant degradate of thiamethoxam in surface water or ground 
water sources of drinking water, it was not included in the EDWCs for 
the thiamethoxam dietary assessment. For the clothianidin assessments, 
the EDWC value of 0.072 ppm for clothianidin was incorporated into the 
acute and chronic dietary assessments. 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 Use of Thiamethoxam on 
Imported Coffee Beans and Condition-of-Registration Residue Data for 
Leaf Lettuce,'' available in the docket EPA-HQ-OPP-2012-0488; 
``Thiamethoxam. Acute and Chronic Aggregate Dietary (Food and Drinking 
Water) Exposure and Risk Assessments for Residues of Thiamethoxam on 
Imported Tea,'' available in the docket EPA-HQ-OPP-2012-0858; and 
``Clothianidin--Aggregate Human Health Risk Assessment of New Uses on 
Strawberry, Pistachio, and Citrus; New Tolerance for Tea; and Revised 
PHI and Tolerance for Pepper and Eggplant (Crop Subgroup 8-10B),'' 
available in the docket EPA-HQ-OPP-2011-0860, at http://www.regulations.gov.
    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 clothianidin, 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 clothianidin. 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.
    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, sod farms, and indoor crack and 
crevice or spot treatments to control insects in residential settings. 
EPA assessed residential exposures for those making applications in 
residential settings as well as for those entering areas previously 
treated with thiamethoxam. Exposures are expected to be short-term 
(i.e., up to 30 days) in duration.
    Adults were assessed for potential short-term dermal and inhalation 
handler exposure from applying thiamethoxam to turf/lawns and from 
indoor crack and crevice/spot treatment applications. Short-term 
postapplication exposures (1 to 30 days of continuous exposure) may 
also occur as a result of activities on treated turf or entering indoor 
areas previously treated with a thiamethoxam indoor crack and crevice 
product. EPA combined non-dietary routes of children's post application 
exposure to obtain an estimate of potential combined exposure. These 
scenarios consisted of dermal postapplication exposure and oral (hand-
to-mouth) exposures for children 1 to < 2 years of age. A complete 
listing of the inputs used in these assessments can be found in the 
document ``Thiamethoxam: Revised Residential Exposure Assessment to 
Support an Amended Import Tolerance for Coffee,'' in docket ID number 
EPA-HQ-OPP-2012-0488 at http://www.regulations.gov.
    Clothianidin is currently registered for the following uses that 
could result in residential exposures: turf, ornamental plants, and/or 
indoor use to control bed bugs. EPA assessed residential exposure using 
the following assumptions: exposures may occur during application of 
products containing clothianidin (handler exposure) as well as 
following application (post-application exposure) and are expected to 
be of short-term (1-30 days) duration.
    Adults were assessed for potential short-term dermal and inhalation 
handler exposure from applying clothianidin to residential turf/home 
lawns and for short-term post-application dermal exposure from contact 
with treated residential and recreational turf home lawns and golf 
courses. There is also potential for post-application dermal and 
inhalation exposure for adults and children resulting from use of 
clothianidin on residential turf, ornamentals (i.e., trees), and indoor 
use to control bed bugs. There is also potential for incidental oral 
post-application exposure for children. Although there is potential for 
adult exposure resulting from both applying the product and post 
application activities, the Agency did not combine exposure estimates 
from adult handler and post application activities because of the 
conservative assumptions and inputs within each exposure scenario. The 
children's

[[Page 18515]]

combined exposure includes only the hand-to-mouth exposure for the 
incidental oral exposure component. To include exposure from object-to-
mouth and soil ingestion in addition to hand-to-mouth would 
overestimate incidental oral exposures for purposes of estimating 
combined residential exposure. Further, because the level of concern 
for dermal exposures (MOEs less than 100) and inhalation exposure (MOEs 
less than 1000) are different, a total aggregate risk index (ARI) 
approach was used instead of the MOE approach. ARIs of greater than 1 
indicate risks are not of concern.
    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 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. 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 Web site at http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional 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; however, there was increased qualitative 
susceptibility because the effects in the pups (reduced brain weight 
and significant changes in brain morphometric measurements) were 
considered to be more severe than findings in the dams (decreased body 
weight gain and food consumption). There is evidence of increased 
quantitative susceptibility for male pups in both 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. The 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) for the most sensitive subgroup 
(pups) observed in the toxicological database.
    3. Conclusion. i. 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 a developmental neurotoxicity (DNT) study 
in rats, and an additional reproduction study in rats. Taking the

[[Page 18516]]

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 (June 23, 2010, 75 FR 35653; FRL-8830-4); (June 22, 
2007, 72 FR 34401). That decision is based on the following findings:
    a. The toxicity database for thiamethoxam is largely complete, 
including acceptable/guideline developmental toxicity, 2-generation 
reproduction, DNT, and immunotoxicity studies. 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) 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. In addition to the 
previous considerations, a 28-day immunotoxicity study in female mice 
was recently received and has undergone a preliminary review. There 
were no immunotoxic effects observed at doses exceeding the limit dose 
of 1,000 mg/kg/day.
    b. For the reasons discussed in Unit III.D.2., there is low concern 
for an increased susceptibility in the young.
    c. 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 14-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. In the 
developmental neurotoxicity study (DNT), there was no evidence of 
neurotoxicity in the dams exposed up to 298.7 mg/kg/day; a dose that 
was associated with decreases in body weight gain and food consumption. 
In pups exposed to 298.7 mg/kg/day, there were significant reductions 
in absolute brain weight and size (i.e., length and width of the 
cerebellum was less in males on day 12, and there were significant 
decreases in Level 3-5 measurements in males and in Level 4-5 
measurements in females on day 63). However, there is low concern for 
this increased qualitative susceptibility observed in the DNT study 
because the doses and endpoints selected for risk assessment are 
protective of the effects in the offspring. As noted previously, for 
risk assessment the Agency selected the NOAEL for testicular effects in 
F1 pups based on two reproductive toxicity studies to be 
protective of all sensitive subpopulations.
    d. 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 percent crop treated (PCT) was made for 
all foods evaluated in the assessments. For the acute and chronic 
assessments, the EDWCs of 131.77 parts per billion (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 clothianidin, the 
modeled estimates are protective of what actual exposures are likely to 
be. EPA used similarly conservative (protective) assumptions to assess 
postapplication exposure to children and adults including incidental 
oral exposure of toddlers. These assessments will not underestimate the 
exposure and risks posed by thiamethoxam.
    ii. 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 (February 11, 2011, 76 FR 7712) (FRL-8858-3). That 
decision is based on the following findings:
    a. The toxicity database for clothianidin is complete. As noted, 
the prior data gap concerning developmental immunotoxicity has been 
addressed by the submission of an

[[Page 18517]]

acceptable developmental immunotoxicity study.
    b. 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.
    c. 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.
    d. 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 population adjusted dose (aPAD) and chronic PAD (cPAD). For 
linear cancer risks, EPA calculates the lifetime probability of 
acquiring cancer given the estimated aggregate exposure. Short-, 
intermediate-, and chronic-term risks are evaluated by comparing the 
estimated aggregate food, water, and residential exposure to the 
appropriate PODs to ensure that an adequate MOE exists.
    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 its 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 28% of its aPAD for children 1 to 2 years old, the population 
group receiving the greatest exposure.
    2. Chronic risk. In examining chronic aggregate risk, EPA has 
assumed that the only pathway of exposure relevant to that time frame 
is dietary exposure. Using this assumption for chronic exposure, EPA 
has concluded that chronic exposure to thiamethoxam from food and water 
will utilize 45% of its 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 28% of its cPAD for 
children 1 to 2 years old, the population group receiving the greatest 
exposure.
    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 430 for adults 
and 450 for children 1 to 2 years. Because EPA's level of concern for 
thiamethoxam is a MOE of 100 or below, these MOEs are not of concern.
    For the clothianidin aggregate assessment, the EPA selected the 
worst-case adult and children exposure scenarios. The treatment of tree 
trunks using a manually-pressurized hand wand presents the worst-case 
exposure estimate for adults, while the bed bug scenario presents the 
worst-case exposure estimates for children 1 to < 2 years old. For 
short- and intermediate-term ``worst-case'' aggregate exposure 
estimates, the ARI for adults is 6.5 and for children 1 to < 2 years 
old, the ARI is estimated at 1.2. ARI estimated values greater than 1.0 
indicate risks are not of concern.
    4. Intermediate-term risk. An intermediate-term adverse effect was 
identified; however, intermediate term exposures (30 to 180 days of 
continuous exposure) are not expected from the registered turf and/or 
indoor uses of thiamethoxam. Intermediate-term risk is assessed based 
on intermediate-term residential exposure plus chronic dietary 
exposure. Because there is no intermediate-term residential exposure 
and chronic dietary exposure has already been assessed under the 
appropriately protective cPAD (which is at least as protective as the 
POD used to assess intermediate-term risk), no further assessment of 
intermediate-term risk is necessary, and EPA relies on the chronic 
dietary risk assessment for evaluating intermediate-term risk for 
thiamethoxam.
    For purposes of performing a clothianidin aggregate assessment, the 
EPA selected the worst-case adult and children exposure scenarios. The 
treatment of tree trunks using a manually-pressurized hand wand 
presents the worst-case exposure estimate for adults, while the bed bug 
scenario presents the worst-case exposure estimates for children 1 to < 
2 years old. For short- and intermediate-term ``worst-case'' aggregate 
exposure estimates, the ARI for adults is 6.5 and for children 1 to <2 
years old, the ARI is estimated at 1.2. ARI estimated values greater 
than 1.0 indicate risks 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. Clothianidin has been classified 
as ``not likely to be a human carcinogen'' and 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.

[[Page 18518]]

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (High Production Liquid 
Chromatography (HPLC) Method AG-675 with ultraviolet (UV) or Mass 
Spectrometry (MS) detection) 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; email address: 
[email protected].

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 United Nations 
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 established MRLs for thiamethoxam in or on coffee at 
0.2 ppm, and tea at 20 ppm. These MRLs are the same as the tolerances 
established for thiamethoxam in the United States.

V. Conclusion

    Therefore, tolerances are established for 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-
yl)methyl]-N'-methyl-N''-nitro-guanidine, calculated as the 
stoichiometric equivalent of thiamethoxam, in or on coffee, green, bean 
at 0.20 ppm and tea, dried at 20 ppm.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances under FFDCA section 408(d) 
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 FFDCA section 408(d), 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 FFDCA section 408(n)(4). 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) (2 U.S.C. 1501 et seq.).
    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) (15 U.S.C. 272 note).

VII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
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 
the rule in the Federal Register. This action 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 15, 2013.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

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

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


0
2. In Sec.  180.565, in the table in paragraph (a), remove the entry 
for ``Coffee, bean, green\1\,'' and footnote 1, and add alphabetically 
entries for ``coffee, green, bean\1\'' new footnote 1, and ``tea, 
dried,'' to read as follows:


Sec.  180.565  Thiamethoxam; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
 
                                * * * * *
Coffee, green, bean \1\...................................          0.20
 
                                * * * * *
Tea, dried \1\............................................         20
 
                                * * * * *
------------------------------------------------------------------------
\1\ There are no U.S. registrations as of March 27, 2013.

* * * * *
[FR Doc. 2013-06759 Filed 3-26-13; 8:45 am]
BILLING CODE 6560-50-P