Clothianidin; Pesticide Tolerances
Federal Register, Volume 77 Issue 168 (Wednesday, August 29, 2012)
Federal Register Volume 77, Number 168 (Wednesday, August 29, 2012)
Rules and Regulations
Pages 52246-52252
From the Federal Register Online via the Government Printing Office www.gpo.gov
FR Doc No: 2012-21215
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
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:
-
General Information
-
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.
-
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.
-
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.
-
-
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.
-
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.
-
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; 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-
HQ-OPP-2010-0217.
-
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
concern.
-
Exposure Assessment
-
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 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.
-
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
-
-
