Environmental Protection Agency (EPA).
ACTION:Final rule.
SUMMARY:This regulation establishes tolerances for residues of clomazone in or on asparagus and soybean, vegetable, succulent. The Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES:This regulation is effective November 10, 2016. Objections and requests for hearings must be received on or before January 9, 2017, 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-2015-0712, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory Public Docket (OPP Docket) in the Environmental Protection Agency Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Public Reading Room is (202) 566-1744, and the telephone number for the OPP Docket is (703) 305-5805. Please review the visitor instructions and additional information about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:Michael Goodis, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone number: (703) 305-7090; email address:RDFRNotices@epa.gov.
SUPPLEMENTARY INFORMATION:I. General InformationA. Does this action apply to me?
You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. The following list of North American Industrial Classification System (NAICS) codes is not intended to be exhaustive, but rather provides a guide to help readers determine whether this document applies to them. Potentially affected entities may include:
Crop production (NAICS code 111). Animal production (NAICS code 112). Food manufacturing (NAICS code 311). Pesticide manufacturing (NAICS code 32532).B. How can I get electronic access to other related information?You may access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
C. How can I file an objection or hearing request?Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 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-2015-0712 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before January 9, 2017. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing (excluding any Confidential Business Information (CBI)) for inclusion in the public docket. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit the non-CBI copy of your objection or hearing request, identified by docket ID number EPA-HQ-OPP-2015-0712, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov. Follow the online instructions for submitting comments. Do not submit electronically any information you consider to be CBI or other information whose disclosure is restricted by statute. Mail: OPP Docket, Environmental Protection Agency Docket Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001. Hand Delivery: To make special arrangements for hand delivery or delivery of boxed information, please follow the instructions athttp://www.epa.gov/dockets/contacts.html.Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available at http://www.epa.gov/dockets.
II. Summary of Petitioned-For ToleranceIn the Federal Register of November 25, 2015 (80 FR 73695) (FRL-9937-14), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP# 5E8402) by Interregional Research No. 4 (IR-4), Rutgers, The State University of New Jersey, 500 College Road East, Suite 201-W, Princeton, NJ 08540. The petition requested that 40 CFR 180.425 be amended by establishing tolerances for residues of the herbicide clomazone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, in or on asparagus at 0.05 parts per million (ppm) and vegetable soybean (edamame) at 0.05 ppm. That document referenced a summary of the petition prepared by FMC Corporation, the registrant, which is available in the docket EPA-HQ-OPP-2015-0712 at http://www.regulations.gov. There were no comments received in response to the notice of filing.
based upon review of the data supporting the petition, EPA has revised the terminology to correct the commodity definition from vegetable soybean (edamame) to soybean, vegetable, succulent.
III. Aggregate Risk Assessment and Determination of SafetySection 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. . . .”Start Printed Page 78914
Consistent with FFDCA section 408(b)(2)(D), and the factors specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure for clomazone including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with clomazone follows.
A. Toxicological ProfileEPA 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.
The primary target of clomazone is the liver, with hepatocellular cytomegaly and increased liver weight noted in the subchronic rat study. No neurotoxicity studies with clomazone are available; however, based on a weight of the evidence approach, EPA has concluded that a neurotoxicity battery is not required for clomazone. This approach considered all of the available hazard and exposure information including: (1) There is no evidence of clinical signs of neurotoxicity or neuropathology in adult animals in subchronic and chronic studies; (2) the liver is the target organ for clomazone, not the neurological system; (3) clomazone is absorbed and rapidly excreted in rats with 97% of the radioactivity excreted within 168 hours; and (4) the point of departure (POD) and endpoint for chronic dietary risk assessment is based on liver effects in rats which appear to be the most sensitive endpoint. There is no quantitative or qualitative evidence of susceptibility in the developmental toxicity study in rabbits or in the 2-generation reproduction toxicity study in rats. In the developmental toxicity study in rats, delayed ossification occurred at doses that produced maternal effects (chromorhinorrhea and abdominogenital staining). Although qualitative susceptibility was observed in the developmental toxicity study in rats, the concern is low since there are clear no-observed-adverse-effect-levels (NOAELs) and lowest-observed-adverse-effect-levels (LOAELs) in the study and this study was used for risk assessment, and therefore, is protective of the developmental effects.
In the rat and mouse carcinogenicity studies, there was no evidence of carcinogenicity. Although the mouse carcinogenicity study was classified as unacceptable/guideline since no systemic toxicity was observed at the highest dose tested, the study was considered adequate to assess the carcinogenicity in mice. EPA has determined that an additional mouse carcinogenicity study is not needed. This finding is based upon the following conclusions: (1) The rat is more sensitive than the mouse for the chronic assessment; (2) the consistent effect in rats (decreased body weight and increased liver weight) has been used as the point of departure for the chronic assessment; (3) a new mouse study would only use doses well above the current POD for the chronic assessment; and (4) even if a new mouse study identified positive carcinogenicity effects, that finding would not result in the adoption of a quantitative linear assessment of cancer risk due to the negative carcinogenicity finding in the rat study and the lack of a positive finding for genotoxicity. Clomazone is classified as “Not Likely to be Carcinogenic to Humans.” Quantification of cancer risk is not required.
Specific information on the studies received and the nature of the adverse effects caused by clomazone as well as the NOAEL and the LOAEL from the toxicity studies can be found at http://www.regulations.gov in document “Clomazone: Human Health Risk Assessment for the Use of Clomazone on Asparagus and Edamame (Vegetable Soybean)” on pages 11-15 in docket ID number EPA-HQ-OPP-2015-0712.
B. Toxicological Points of Departure/Levels of Concernonce 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 clomazone used for human risk assessment used for human risk assessment is shown in Table 1 of this unit.
| Exposure/scenario | Point of departure and uncertainty/ safety factors | RfD, PAD, LOC for risk assessment | Study and toxicological effects |
|---|---|---|---|
| Acute dietary (General population including infants and children) | An endpoint was not selected for the general population because no adverse effect in adult animals was identified that resulted from a single exposure. A risk assessment is not required for this population subgroup. | ||
| Acute dietary (Females 13 to 49 years of age) | NOAEL = 100 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x | Acute RfD = 1.0 mg/kg/day aPAD = 1.0 mg/kg/day | Developmental Toxicity Study—Rats (MRID 00150291). LOAEL = 300 mg/kg/day based on indications of delayed ossification in the form of either partial ossification or the absence of the manubrium, sternebrae 3-4, xiphoid, caudal vertebrae, and meta-carpals. |
| Chronic dietary (All populations) | NOAEL= 84.4 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x | Chronic RfD = 0.84 mg/kg/day cPAD = 0.84 mg/kg/day | Two Year Chronic Toxicity Study—Rats (MRID 00132586). NOAEL = 84.4/112.9 mg/kg/day, males/females (highest dose tested). LOAEL was not attained Co-critical 90-day Oral Rat Study (MRID 00132586). |
| NOAEL = 135.2/160.9 mg/kg/day, males/females. | |||
| LOAEL = 273/319.3 mg/kg/day, males/females, based on decreased body weight, body weight gains, food consumption and increased absolute and relative liver weights in females and increased absolute liver weights in males. | |||
| Co-critical 2-Generation Reproduction Toxicity Study (MRID 00151108). | |||
| Parental LOAEL = 100 mg/kg/day based on statistically significantly decreased body weight & body weight gain during pre-mating, and decreased body weight during gestation & lactation M & F. In addition, decreased food consumption in females and hydronephritic kidneys in males. | |||
| Cancer (Oral, dermal, inhalation) | “Not Likely to be Carcinogenic to Humans.” Quantitative assessment of cancer risk is not required. | ||
| FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level of concern. mg/kg/day = milligram/kilogram/day. NOAEL = no-observed-adverse-effect-level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). | |||
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to clomazone, EPA considered exposure under the petitioned-for tolerances as well as all existing clomazone tolerances in 40 CFR 180.425. EPA assessed dietary exposures from clomazone 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 clomazone. In estimating acute dietary exposure, EPA used the Dietary Exposure evaluation Model software with the Food Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data from the U.S. Department of Agriculture's (USDA's) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA incorporated tolerance-level residues, 100 percent crop treated (PCT) for all commodities, and DEEM 7.81 default processing factors as appropriate.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used DEEM-FCID Version 3.16. This software uses 2003-2008 food consumption data from USDA's NHANES/WWEIA. As to residue levels in food, EPA incorporated tolerance-level residues, 100 PCT for all commodities, and DEEM 7.81 default processing factors as appropriate.
iii. Cancer. based on the data summarized in Unit III.A., EPA has concluded that clomazone does not pose a cancer risk to humans. Therefore, a dietary exposure assessment for the purpose of assessing cancer risk is unnecessary.
iv. Anticipated residue and PCT information. EPA did not use anticipated residue or PCT information in the dietary assessment for clomazone. Tolerance level residues and 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. In drinking water, the residues of concern include clomazone parent and its degradate FMC65317 (N-[(2-chlorophenyl)methyl]-3-hydroxy-2,2-dimenthylpropanamide). The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for clomazone in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of clomazone. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide.
based on the Tier 1 Rice Model and Pesticide Root Zone Model Ground Water (PRZM GW), the estimated drinking water concentrations (EDWCs) of clomazone for acute exposures are estimated to be 550 parts per billion (ppb) for surface water and 85.7 ppb for ground water. The EDWCs of clomazone for chronic exposures for non-cancer assessments are estimated to be 550 ppb for surface water and 77.4 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For both acute and chronic dietary risk assessment, the water concentration value of 550 ppb was used to assess the contribution to drinking water.
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). Clomazone is not registered for any specific use patterns that would result in residential exposure.
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 Start Printed Page 78916substances that have a common mechanism of toxicity.”
EPA has not found clomazone to share a common mechanism of toxicity with any other substances, and clomazone does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that clomazone does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's Web site athttp://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.
D. Safety Factor for Infants and Children1. 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 was no evidence of increased quantitative or qualitative susceptibility in the prenatal developmental toxicity study in rabbits or in the reproductive toxicity study in rats with clomazone. In the developmental toxicity study in rats, effects in the fetuses (delayed ossification) occurred at doses that produced maternal effects (chromorhinorrhea and abdominogenital staining) but were qualitatively more severe. Although qualitative susceptibility was observed in the developmental toxicity study in rats, the concern is low since there are clear NOAELs and LOAELs in this study and the NOAEL in the study was used as the POD for assessment of acute risk. EPA's assessment of acute risk is therefore protective of any developmental effects.
3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were reduced to 1X. That decision is based on the following findings:
i. The toxicity database for clomazone is complete.
ii. There is no indication that clomazone is a neurotoxic chemical and there is no need for additional UFs to account for neurotoxicity.
iii. For the reasons described above in Unit III.D.2., there is low concern regarding increased susceptibility in the young from exposure to clomazone.
iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100 PCT and tolerance-level residues. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to clomazone in drinking water. There are no existing or pending residential uses. Therefore, these assessments will not underestimate the exposure and risks posed by clomazone.
E. Aggregate Risks and Determination of SafetyEPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse effect resulting from a single oral exposure was identified and no acute dietary endpoint was selected for the general population including infants and children. Therefore, clomazone is not expected to pose an acute risk to these groups.
However, an acute endpoint was identified for females 13 to 49 years old due to effects observed in fetuses. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to clomazone will occupy 3.0% of the aPAD for females 13 to 49 years old.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to clomazone from food and water will utilize 3.6% of the cPAD for all infants <1 year old, the population group receiving the greatest exposure. There are no residential uses for clomazone.
3. Short- and intermediate-term risk. Short- and intermediate-term aggregate exposures take into account short- and intermediate-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).
Clomazone is not registered for any use patterns that would result in short- or intermediate-term residential exposure. Because there are no short- or intermediate-term residential exposures and chronic dietary exposure has already been assessed under the appropriately protective cPAD (which is at least as protective as the POD used to assess short- and intermediate-term risks), no further assessment of short- and intermediate-term risks are necessary.
4. Aggregate cancer risk for U.S. population. based on the lack of evidence of carcinogenicity in rodent carcinogenicity studies, along with the data summarized in Unit III.A., clomazone 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 clomazone residues.
IV. Other ConsiderationsA. Analytical Enforcement MethodologyAdequate enforcement methodology (gas chromatography (GC) using a nitrogen phosphorus detector (NPD) or mass spectrometer (MS)) is available to enforce the tolerance expression.
The method may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; email address: residuemethods@epa.gov.
B. International Residue LimitsIn making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4). The Codex Alimentarius is a joint United Nations Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an international food safety standards-setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that Start Printed Page 78917EPA explain the reasons for departing from the Codex level.
The Codex has not established any MRLs for clomazone.
V. Conclusion
Therefore, tolerances are established for residues of clomazone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, in or on asparagus at 0.05 ppm and soybean, vegetable, succulent at 0.05 ppm.
