52246 Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 

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: August 17, 2012. 

Lois Rossi, 

Director, Registration Division, Office of 

Pesticide Programs. 

Therefore, 40 CFR chapter I is 

amended as follows: 

PART 180—[AMENDED] 

■ 1. The authority citation for part 180 

continues to read as follows: 

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

■ 2. Section 180.361 is amended by 

alphabetically adding the following 

commodities to the table in paragraph 

(a) to read as follows: 

§ 180.361 Pendimethalin; tolerances for 

residues. 

(a) * * * 

Commodity Parts per 

million 

* * * * * 

Brassica, leafy greens, subgroup 5B ......................... 0 .20 

* * * * * 

Fruit, small vine climbing, 

except grape, subgroup 

13–07E ............................ 0 .10 

* * * * * 

Lettuce, leaf ........................ 4 .0 

Melon subgroup 9A ............ 0 .10 

* * * * * 

Turnip greens ..................... 0 .20 

* * * * * 

Vegetable, soybean, succulent ............................... 0 .10 

* * * * * 

* * * * * 

[FR Doc. 2012–21361 Filed 8–28–12; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

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. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this action apply to me? 

You may be potentially affected by 

this action if you are an agricultural 

producer, food manufacturer, or 

pesticide manufacturer. Potentially 

affected entities may include, but are 

not limited to those engaged in the 

following activities: 

• Crop production (NAICS code 111). 

• Animal production (NAICS code 

112). 

• Food manufacturing (NAICS code 

311). 

• Pesticide manufacturing (NAICS 

code 32532). 

This listing is not intended to be 

exhaustive, but rather to provide a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The North American 

Industrial Classification System 

(NAICS) codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

B. How can I access electronic copies of 

this document? 

In addition to accessing electronically 

available documents at http:// 

www.regulations.gov, you may access 

this Federal Register document 

electronically through the EPA Internet 

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. 

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Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 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 children. 

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; parentonly 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 ATMGpyruvate 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. 

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52248 Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 

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-observedadverse-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–HQ–OPP–2010– 

0217. 

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

Exposure/scenario 

Point of departure 

and uncertainty/ 

safety factors 

RfD, PAD, LOC for 

risk assessment Study and toxicological effects 

Acute dietary (Females 13–49 years of 

age).

NOAEL = 25 milligrams/kilograms/ 

day (mg/kg/day) 

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute RfD = 0.25 

mg/kg/day 

aPAD = 0.25mg/kg/ 

day 

Rabbit developmental study 

LOAEL = 75 mg/kg/day based on increased litter incidence of a missing lobe of the lung 

Acute dietary (General population) ........ NOAEL = 25 mg/ 

kg/day 

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute RfD = 0.25 

mg/kg/day 

aPAD = 0.25 mg/ 

kg/day 

Special neurotoxicity/pharmacological study in mice 

LOAEL = 50 mg/kg/day based on transient signs of decreased spontaneous motor activity, tremors and deep 

respirations 

Chronic dietary (All populations including infants and children).NOAEL= 9.8 mg/ 

kg/day 

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD = 

0.098 mg/kg/day 

cPAD = 0.098 mg/ 

kg/day 

2-Generation reproduction study 

LOAEL = 31.2 mg/kg/day based on decreased body 

weight gains and delayed sexual maturation, decreased 

absolute thymus weights in F1 pups and increased stillbirths in both generations 

Incidental oral (Short and intermediate 

term).

NOAEL= 9.8 mg/ 

kg/day 

UFA = 10X

UFH = 10X

FQPA SF = 1X

LOC for MOE = 

100 

2-Generation reproduction study 

LOAEL = 31.2 mg/kg/day based on decreased body 

weight gains and delayed sexual maturation, decreased 

absolute thymus weights in F1 pups and increased stillbirths in both generations 

Dermal (All durations) ............................ Oral study NOAEL 

= 9.8 mg/kg/day 

(dermal absorption rate = 1%) 

UFA = 10X

UFH = 10X

FQPA SF = 1X

LOC for MOE = 

100 

2-Generation reproduction study 

LOAEL = 31.2 mg/kg/day based on decreased body 

weight gains and delayed sexual maturation, decreased 

absolute thymus weights in F1 pups and increased stillbirths in both generations 

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Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 52249 

TABLE 1—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR CLOTHIANIDIN FOR USE IN HUMAN HEALTH RISK

ASSESSMENT—Continued 

Exposure/scenario 

Point of departure 

and uncertainty/ 

safety factors 

RfD, PAD, LOC for 

risk assessment Study and toxicological effects 

Inhalation (All durations) ........................ Oral study 

NOAEL= 9.8 mg/ 

kg/day (inhalation absorption 

rate = 100%) 

UFA = 10X

UFH = 10X

FQPA SF = 1X

LOC for MOE = 

100 

2-Generation reproduction study 

LOAEL = 31.2 mg/kg/day based on decreased body 

weight gains and delayed sexual maturation, decreased 

absolute thymus weights in F1 pups and increased stillbirths in both generations 

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 concern. 

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 lowgrowing 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 ATGacetate 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 

unnecessary. 

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 

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52250 Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 

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 nonoccupational, 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 postapplication contact and golfer 

postapplication contact. For toddlers, 

short- and intermediate-term 

postapplication incidental oral (hand-tomouth 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 factor. 

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 toxicity. 

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 

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Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 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 healthprotective 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 shortand intermediate-term residential 

exposure and the Agency has 

determined that it is appropriate to 

aggregate chronic exposure through food 

and water with short- and intermediateterm residential exposures to 

clothianidin. Using the exposure 

assumptions described in this unit for 

short- and intermediate-term exposures, 

EPA has concluded the combined shortand 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, grain. 

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-methyl2-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 

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52252 Federal Register / Vol. 77, No. 168 / Wednesday, August 29, 2012 / Rules and Regulations 

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 note). 

VII. Congressional Review Act 

The Congressional Review Act, 5 

U.S.C. 801 et seq., generally provides 

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report to each House of 

the Congress and to the Comptroller 

General of the United States. EPA will 

submit a report containing this rule and 

other required information to the U.S. 

Senate, the U.S. House of 

Representatives, and the Comptroller 

General of the United States prior to 

publication of this final rule in the 

Federal Register. This final rule is not 

a ‘‘major rule’’ as defined by 5 U.S.C. 

804(2). 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: August 17, 2012. 

Daniel J. Rosenblatt, 

Acting Director, Registration Division, Office 

of Pesticide Programs. 

Therefore, 40 CFR chapter I is 

amended as follows: 

PART 180—[AMENDED] 

■ 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: 

§ 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] 

BILLING CODE 6560–50–P 

DEPARTMENT OF DEFENSE 

Defense Acquisition Regulations 

System 

48 CFR Parts 201 and 212 

RIN 0750–AH65 

Defense Federal Acquisition 

Regulation Supplement: Inflation 

Adjustment of Threshold for 

Acquisition of Right-Hand Drive 

Passenger Sedans (DFARS Case 2012– 

D016) 

AGENCY: Defense Acquisition 

Regulations System, Department of 

Defense (DoD). 

ACTION: Final rule. 

SUMMARY: DoD is adopting as final, 

without change, an interim rule 

amending the Defense Federal 

Acquisition Regulation Supplement 

(DFARS) to implement a section of the 

National Defense Authorization Act for 

Fiscal Year 2012 that requires 

adjustment of the statutory dollar 

limitation on the acquisition of righthand drive passenger sedans. 

DATES: Effective Date: August 29, 2012. 

FOR FURTHER INFORMATION CONTACT: Ms. 

Amy Williams, telephone 571–372– 

6106. 

SUPPLEMENTARY INFORMATION: 

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