[Federal Register Volume 77, Number 168 (Wednesday, August 29, 2012)]
[Rules and Regulations]
[Pages 52246-52252]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-21215]



40 CFR Part 180

[EPA-HQ-OPP-2010-0217; FRL-9360-4]

Clothianidin; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.


SUMMARY: This regulation establishes tolerances for residues of 
clothianidin in or on rice, grain at 0.01 ppm. Valent U.S.A. 
Corporation requested these tolerances under the Federal Food, Drug, 
and Cosmetic Act (FFDCA).

DATES: This regulation is effective August 29, 2012. Objections and 
requests for hearings must be received on or before October 29, 2012, 
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-2010-0217, is available at http://www.regulations.gov or at the OPP Docket in the Environmental 
Protection Agency Docket Center (EPA/DC), located in EPA West, 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: Marianne Lewis, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8043; email address: lewis.marianne@epa.gov.


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 

B. How can I access electronic copies of this document?

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

C. Can I file an objection or hearing request?

    Under section 408(g) of FFDCA, 21 U.S.C. 346a, any person may file 
an objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection or request a 
hearing on this regulation in accordance with the instructions provided 
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify 
docket ID number EPA-HQ-OPP-2010-0217 in the subject line on the first 
page of your submission. All requests must be in writing, and must be 
mailed or delivered to the Hearing Clerk as required by 40 CFR part 178 
on or before October 29, 2012.
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing that does not contain any CBI for inclusion in the public 
docket that is described in ADDRESSES. Information not marked 
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA 
without prior notice. Submit this copy, identified by docket ID number 
EPA-HQ-OPP-2010-0217, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments.

[[Page 52247]]

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), Mail Code: 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. Petition for Tolerance

    In the Federal Register of May 6, 2011 (76 FR 26291) (FRL-8870-3), 
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 1F7832) 
by Valent U.S.A. Corporation, P.O. Box 8025, Walnut Creek, CA 94596. 
The petition requested that 40 CFR 180.586 be amended by establishing 
tolerances for residues of the insecticide clothianidin, (E)-1-(2-
chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine, in or on 
rice, grain at 0.01 ppm. That notice referenced a summary of the 
petition prepared by Valent U.S.A. Corporation, the registrant, which 
is available to the public in the docket, http://www.regulations.gov. 
There were no comments received in response to the notice of filing.
    Valent U.S.A. Corporation requested tolerances for residues of 
clothianidin to support rice, grain uses.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue * * 
    Consistent with section 408(b)(2)(D) of FFDCA, and the factors 
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure for the petitioned-for 
tolerances for residues of clothianidin in or on rice, grain at 0.01 
ppm. EPA's assessment of exposures and risks associated with 
clothianidin 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 
    EPA considered the toxicity of clothianidin as well as several 
metabolites and degradates in conducting this risk assessment. 
Metabolites/degradates of concern in plants include parent and TMG for 
leafy and root and tuber vegetables; parent-only for other crops; and 
parent, TZNG and MNG for rotational crops. For livestock commodities, 
the metabolites/degradates of concern include: Parent and TZU, TZG, 
TZNG and ATMG-pyruvate for ruminants; and parent and TZU, TZG, TZNG, 
and ATG-acetate for poultry. Acute toxicity and genotoxicity data are 
available for several metabolites/degradates of clothianidin. Given 
that the points of departure used for risk assessment are well below 
the LD50 levels observed in the acute toxicology studies and 
that clothianidin and its metabolites/degradates of toxicological 
concern are similar in structure, EPA is assuming that these compounds 
are toxicologically equivalent to clothianidin with respect to the 
endpoints being used for risk assessment.
    Clothianidin and its metabolites and degradates have relatively low 
acute toxicity via oral, dermal and inhalation routes of exposure; 
however, acute oral administration of clothianidin in mouse and the TMG 
metabolite in rat showed evidence of increased relative toxicity. There 
is no evidence of dermal sensitization or eye irritation with the 
exception of the clothianidin-triazan intermediate, which is a dermal 
sensitizer. The available data indicate that there are no consistent 
target organs in mammals; however, some effects noted in the liver, 
hematopoietic system and kidney are similar to effects from other 
neonicotinoid insecticides.
    In subchronic oral studies, the dog seemed to be more sensitive to 
clothianidin than the rat. In addition to decreases in body weight and 
body weight gains observed in both animals, dogs also displayed 
decreased white blood cells, albumin and total protein, as well as some 
anemia. Long-term dietary administration of clothianidin did not result 
in a wider spectrum of effects in the dog; in contrast, the chronic 
feeding studies in rats showed additional effects in the liver, ovaries 
and kidneys. In the mouse chronic oral study, increases in vocalization 
and decreases in body weight and body weight gain were noted.
    Based on the lack of significant tumor increases in two adequate 
rodent carcinogenicity studies, EPA has classified clothianidin as 
``not likely to be carcinogenic to humans.'' A bone marrow micronucleus 
assay in mice showed that clothianidin is neither clastogenic nor 
aneugenic up to a toxic oral dose. Additionally, a study on the livers 
of Wistar male mice showed no induction of unscheduled DNA synthesis up 
to the limit dose; therefore, mutagenicity is not of concern.
    Clinical signs of neurotoxicity were exhibited in both rats 
(decreased arousal, motor activity and locomotor activity) and mice 
(decreased spontaneous motor activity, tremors and deep respirations) 
in acute neurotoxicity studies following exposure by gavage; however, 
no indications of neurotoxicity were observed following dietary 
exposure in the subchronic neurotoxicity study in rats.
    There was no evidence of increased quantitative or qualitative 
susceptibility of rat or rabbit fetuses following in utero exposure to 
clothianidin in developmental studies; however, increased quantitative 
susceptibility of rat pups was seen in both the reproduction and 
developmental neurotoxicity studies. In the rat reproduction study, 
offspring toxicity (decreased body weight gains and absolute thymus 
weights in pups, delayed sexual maturation and an increase in 
stillbirths) was observed in the absence of maternal effects. In the 
developmental neurotoxicity study in rats, offspring effects (decreased 
body weights, body weight gains, motor activity and acoustic startle 
response amplitude) were noted at doses lower than those resulting in 
maternal toxicity.

[[Page 52248]]

    Decreased absolute and relative thymus and spleen weights were 
observed in multiple studies; these studies showed possible evidence of 
effects on the immune system. In addition, juvenile rats in the rat 
reproduction study appeared to be more susceptible to these effects. 
However, a guideline immunotoxicity study showed no evidence of 
clothianidin-mediated immunotoxicity in adult rats and a developmental 
immunotoxicity study demonstrated no increased susceptibility for 
offspring with regard to immunotoxicity.
    Specific information on the studies received and the nature of the 
adverse effects caused by clothianidin 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 document ``Clothianidin: Human Health Risk 
Assessment for Requested Foliar Uses on Rice, Seed Treatment on Leafy 
Vegetables, Increased Application Rate for Vegetables, and Expanded 
Uses on Fruiting Vegetables and Pome Fruit.'' in docket ID number EPA-

B. Toxicological Endpoints

    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 Clothianidin used for 
human risk assessment is shown in Table 1 of this unit.

 Table 1--Summary of Toxicological Doses and Endpoints for Clothianidin for Use in Human Health Risk Assessment
                                    Point of departure
        Exposure/scenario            and uncertainty/     RfD, PAD, LOC for     Study and toxicological effects
                                      safety factors       risk assessment
Acute dietary (Females 13-49       NOAEL = 25            Acute RfD = 0.25 mg/ Rabbit developmental study
 years of age).                     milligrams/           kg/day              LOAEL = 75 mg/kg/day based on
                                    kilograms/day (mg/   aPAD = 0.25mg/kg/     increased litter incidence of a
                                    kg/day)               day.                 missing lobe of the lung
                                   UFA = 10X...........
                                   UFH = 10X...........
                                   FQPA SF = 1X........
Acute dietary (General             NOAEL = 25 mg/kg/day  Acute RfD = 0.25 mg/ Special neurotoxicity/
 population).                      UFA = 10X...........   kg/day               pharmacological study in mice
                                   UFH = 10X...........  aPAD = 0.25 mg/kg/   LOAEL = 50 mg/kg/day based on
                                   FQPA SF = 1X........   day.                 transient signs of decreased
                                                                               spontaneous motor activity,
                                                                               tremors and deep respirations
Chronic dietary (All populations   NOAEL= 9.8 mg/kg/day  Chronic RfD = 0.098  2-Generation reproduction study
 including infants and children).  UFA = 10X...........   mg/kg/day           LOAEL = 31.2 mg/kg/day based on
                                   UFH = 10X...........  cPAD = 0.098 mg/kg/   decreased body weight gains and
                                   FQPA SF = 1X........   day.                 delayed sexual maturation,
                                                                               decreased absolute thymus weights
                                                                               in F1 pups and increased
                                                                               stillbirths in both generations
Incidental oral (Short and         NOAEL= 9.8 mg/kg/day  LOC for MOE = 100    2-Generation reproduction study
 intermediate term).               UFA = 10X...........                       LOAEL = 31.2 mg/kg/day based on
                                   UFH = 10X...........                        decreased body weight gains and
                                   FQPA SF = 1X........                        delayed sexual maturation,
                                                                               decreased absolute thymus weights
                                                                               in F1 pups and increased
                                                                               stillbirths in both generations
Dermal (All durations)...........  Oral study NOAEL =    LOC for MOE = 100    2-Generation reproduction study
                                    9.8 mg/kg/day                             LOAEL = 31.2 mg/kg/day based on
                                    (dermal absorption                         decreased body weight gains and
                                    rate = 1%)                                 delayed sexual maturation,
                                   UFA = 10X...........                        decreased absolute thymus weights
                                   UFH = 10X...........                        in F1 pups and increased
                                   FQPA SF = 1X........                        stillbirths in both generations

[[Page 52249]]

Inhalation (All durations).......  Oral study NOAEL=     LOC for MOE = 100    2-Generation reproduction study
                                    9.8 mg/kg/day                             LOAEL = 31.2 mg/kg/day based on
                                    (inhalation                                decreased body weight gains and
                                    absorption rate =                          delayed sexual maturation,
                                    100%)                                      decreased absolute thymus weights
                                   UFA = 10X...........                        in F1 pups and increased
                                   UFH = 10X...........                        stillbirths in both generations
                                   FQPA SF = 1X........
Cancer (Oral, dermal, inhalation)  ``Not likely to be Carcinogenic to Humans''
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
  of the human population (intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. PAD = population
  adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to clothianidin, EPA considered exposure from the petitioned-
for tolerances as well as all existing clothianidin tolerances in 40 
CFR 180.586. EPA assessed dietary exposures from clothianidin in food 
as follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure.
    Such effects were identified for clothianidin. 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 from use of clothianidin, EPA used maximum field trial 
values, empirical processing factors and assumed 100 percent crop 
treated (PCT) for all commodities. Clothianidin is a major metabolite 
of thiamethoxam, and there are a number of crops for which uses of both 
clothianidin and thiamethoxam have been registered. The labels for the 
various end-use products containing these active ingredients prohibit 
the application of both active ingredients to the same crop during a 
growing cycle. Due to that restriction and the assumption of 100 PCT, a 
single value reflecting the greatest clothianidin residue from either 
active ingredient has been used for crops listed for use with both 
active ingredients (versus combined estimates from clothianidin and 
from thiamethoxam). Generally, this assessment uses the established or 
recommended clothianidin tolerance for crops having tolerances for both 
compounds (the exception being low-growing berry, subgroup 13-07G, 
which is based on observed clothianidin residues in thiamethoxam 
strawberry field trials). For foods with thiamethoxam tolerances but 
without clothianidin tolerances, maximum residues of clothianidin 
observed in thiamethoxam field trials have been used in these 
assessments. These include meats, meat by-products, artichoke, tropical 
fruits, coffee, hop, mint, rice, and strawberry. The metabolism of 
clothianidin is complex, with a few major (> 10% of the total 
radioactive residues) and numerous minor metabolites. Metabolites/
degradates of concern in plants include clothianidin and TMG for leafy 
and root and tuber vegetables; parent-only for other crops; and parent, 
TZNG and MNG for rotational crops. For livestock commodities, the 
metabolites of concern include: parent and TZU, TZG, TZNG, and ATMG-
pyruvate for ruminants; and parent and TZU, TZG, TZNG, and ATG-acetate 
for poultry. For leafy vegetables the EPA required analysis for 
residues of TMG along with parent in field trial samples. Residues of 
TMG were shown to occur in leafy vegetables at levels approximately 10-
fold below those of clothianidin. EPA has not included these 
metabolites in the tolerance expression for plant or animal commodities 
because the metabolites are only found in certain commodities, 
including the metabolites would create tolerance harmonization issues 
with Canada, and monitoring residues of clothianidin based on parent 
only would be representative of total clothianidin residues and thus 
adequate for enforcement. Because the metabolites are not included in 
the tolerance expressions, an adjustment factor of 1.1 has been 
incorporated into the assessment for leafy vegetables to account for 
the presence of the metabolite TMG, and an adjustment factor of 1.5 has 
been incorporated for livestock-derived commodities (milk) to account 
for the presence of metabolites TZU, TZG, TZNG, ATMG-pyruvate and ATG-
acetate. The 1.1 adjustment factor is based on field trial data showing 
TMG does not exceed 10% of the parent compound residue level in leafy 
vegetables and the 1.5 factor was based on metabolism data.
    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 assessed chronic 
dietary exposure using the same residue information and assumptions 
regarding metabolites/degradates as in the acute exposure analysis.
    iii. Cancer. Based on the lack of evidence of carcinogenicity in 
two adequate rodent carcinogenicity studies, EPA has classified 
clothianidin as ``not likely to be carcinogenic to humans.'' Therefore, 
a quantitative exposure assessment to evaluate cancer risk is 
    iv. Anticipated residue and percent crop treated (PCT) information.
    For food with thiamethoxam tolerances but without clothianidin 
tolerances, maximum residues of clothianidin observed in thiamethoxam 
field trials have been used in these assessments. For all commodities, 
100 PCT was assumed.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for clothianidin in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of

[[Page 52250]]

clothianidin. 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 First Index Reservoir Screening Tool (FIRST) and 
Screening Concentration in Ground Water (SCI-GROW) models, the 
estimated drinking water concentrations (EDWCs) of clothianidin for 
surface water are estimated to be 72 parts per billion (ppb) for acute 
exposures and <72 ppb for chronic exposures.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. The EDWC of 72 ppb was used to 
account for residues of clothianidin in both the acute and chronic 
dietary risk assessments.
    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).
    Clothianidin is currently registered for use on turf. Residential 
handler exposure is not expected from the currently registered or 
proposed uses of clothianidin since these products are to be applied by 
commercial applicators. Adult short- and intermediate-term 
postapplication exposures were assessed for dermal exposures from 
commercial applications (via granular push-type spreaders), dermal 
post-application contact and golfer postapplication contact. For 
toddlers, short- and intermediate-term postapplication incidental oral 
(hand-to-mouth and soil ingestion) and dermal risks were assessed for 
exposure to treated turf.
    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.''
    Clothianidin is a member of the neonicotinoid class of pesticides 
and is a metabolite of another neonicotinoid, thiamethoxam. Structural 
similarities or common effects do not constitute a common mechanism of 
toxicity. Evidence is needed to establish that the chemicals operate by 
the same, or essentially the same sequence of major biochemical events 
(EPA, 2002). Although clothianidin and thiamethoxam bind selectively to 
insect nicotinic acetylcholine receptors (nAChR), the specific binding 
site(s)/receptor(s) for clothianidin, thiamethoxam, and the other 
neonicotinoids are unknown at this time. Additionally, the commonality 
of the binding activity itself is uncertain, as preliminary evidence 
suggests that clothianidin operates by direct competitive inhibition, 
while thiamethoxam is a noncompetitive inhibitor. Furthermore, even if 
future research shows that neonicotinoids share a common binding 
activity to a specific site on insect nAChRs, 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 clothianidin is based on unrelated 
effects in mammals, including changes in body and thymus weights, 
delays in sexual maturation, and still births. Additionally, the most 
sensitive toxicological effect in mammals differs across the 
neonicotinoids (such as testicular tubular atrophy with thiamethoxam, 
and mineralized particles in thyroid colloid with imidaclopid). Thus, 
there is currently no evidence to indicate that neonicotinoids share 
common mechanisms of toxicity, and EPA is not following a cumulative 
risk approach based on a common mechanism of toxicity for the 
neonicotinoids. For information regarding EPA's efforts to determine 
which chemicals have a common mechanism of toxicity and to evaluate the 
cumulative effects of such chemicals, see the policy statements 
concerning common mechanism determinations and procedures for 
cumulating effects from substances found to have a common mechanism 
released by OPP on EPA's Web site at http://www.epa.gov/pesticides/cumulative/.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(c) of FFDCA provides that EPA 
shall apply an additional 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 
    2. Prenatal and postnatal sensitivity. There is no indication of 
increased quantitative or qualitative susceptibility, as compared to 
adults, of rat and rabbit fetuses following in utero exposure to 
clothianidin in developmental studies. However, increased quantitative 
susceptibility was observed in both the developmental neurotoxicity and 
rat multi-generation reproduction studies. In the developmental 
neurotoxicity study, offspring toxicity (decreased body weight gains, 
motor activity and acoustic startle response) was seen at a lower dose 
than that which caused maternal toxicity. In the two-generation rat 
reproduction study, offspring toxicity (decreased body weight gains, 
delayed sexual maturation in males, decreased absolute thymus weights 
in F1 pups of both sexes and an increase in stillbirths in both 
generations) was seen at a dose lower than that which caused parental 
    3. Conclusion. 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 data base, and evidence showing 
that juvenile rats in the two-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

[[Page 52251]]

decision is based on the following findings:

    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.
    i. There are no residual concerns regarding potential pre- and 
postnatal toxicity in the young. 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 pre- 
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.
    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 has been selected as the POD 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 pre- and postnatal 
toxicity after establishing toxicity endpoints and traditional UFs 
to be used in the risk assessment for clothianidin.
    ii. 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 maximum field trial residues, adjustment 
factors from metabolite data, empirical processing factors, and 100 
PCT for all commodities. Additionally, EPA made conservative 
(protective) assumptions in the ground and surface water modeling 
used to assess exposure to clothianidin in drinking water. EPA used 
similarly conservative assumptions to assess postapplication 
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 
aPAD and cPAD. For linear cancer risks, EPA calculates the probability 
of additional cancer cases given the estimated aggregate exposure. 
Short-, intermediate-, and chronic-term risks are evaluated by 
comparing the estimated aggregate food, water, and residential exposure 
to the appropriate POD 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 clothianidin will occupy 24% of the aPAD for children 1-2 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 
clothianidin from food and water will utilize 21% of the cPAD for 
children 1-2 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 
clothianidin is not expected.
    3. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposure takes into account short- and intermediate-term 
residential exposure plus chronic exposure to food and water 
(considered to be a background exposure level).
    Clothianidin is currently registered for use on turf that could 
result in short- and intermediate-term residential exposure and the 
Agency has determined that it is appropriate to aggregate chronic 
exposure through food and water with short- and intermediate-term 
residential exposures to clothianidin. Using the exposure assumptions 
described in this unit for short- and intermediate-term exposures, EPA 
has concluded the combined short- and intermediate-term food, water, 
and residential exposures result in aggregate MOEs of greater than 450 
for all population subgroups. As the aggregate MOEs are greater than 
100 (the LOC) for all population subgroups, including infants and 
children, short- and intermediate-term aggregate exposures to 
clothianidin are not of concern to EPA.
    4. Aggregate cancer risk for U.S. population. Based on the lack of 
evidence of carcinogenicity in mice and rats at doses that were judged 
to be adequate to assess the carcinogenic potential, clothianidin was 
classified as ``not likely to be carcinogenic to humans,'' and is not 
expected to pose a cancer risk to humans.
    5. 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 clothianidin residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology is available to enforce the 
tolerance expression. This method involves extraction of residues with 
acetonitrile/water, cleanup using solid phase extraction (SPE) 
cartridges, and analysis of clothianidin by LC/MS/MS. 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: residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international 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 clothianidin in/on rice, 

C. Revisions to Petitioned-For Tolerances

    The tolerance is considered appropriate as proposed; therefore, no 
revisions were needed.

V. Conclusion

    Therefore, tolerances are established for residues of clothianidin, 
(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine, in 
or on rice, grain at 0.01 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

[[Page 52252]]

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) (Pub. L. 104-4).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 

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: August 17, 2012.
Daniel J. Rosenblatt,
Acting Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:


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

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

2. Section 180.586 is amended by revising paragraph (a)(1) introductory 
text, and by alphabetically adding the commodity ``rice, grain'' in the 
table in paragraph (a)(1) to read as follows:

Sec.  180.586  Clothianidin; tolerances for residues.

    (a) General. (1) Tolerances are established for residues of the 
insecticide clothianidin, including its metabolites and degradates. 
Compliance with the tolerance levels specified below is to be 
determined by measuring only clothianidin, (E)-N-[(2-Chloro-5-
thiazolyl)methyl]-N' -methyl-N'' -nitroguanidine, in or on the 
following raw agricultural commodities:

                      Commodity                                            Parts per million
                                                  * * * * * * *
Rice, grain                                                                                                0.01
                                                  * * * * * * *

* * * * *
[FR Doc. 2012-21215 Filed 8-28-12; 8:45 am]