Source: https://www.federalregister.gov/documents/2017/10/16/2017-22357/fenpicoxamid-pesticide-tolerances
Timestamp: 2017-11-18 16:21:47
Document Index: 792799656

Matched Legal Cases: ['art 178', 'art 178', 'art 178', 'art 2', 'art 180', '§\u2009180', '§\u2009180']

Federal Register :: Fenpicoxamid; Pesticide Tolerances
Fenpicoxamid; Pesticide Tolerances
A Rule by the Environmental Protection Agency on 10/16/2017
This regulation is effective October 16, 2017. Objections and requests for hearings must be received on or before December 15, 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).
47996-48000 (5 pages)
EPA-HQ-OPP-2016-0392
FRL-9966-73
Human Health Risk Assessment to Establish Tolerances for...
Chronic Dietary Exposure and Risk Assessment (Food Only) for...
Dow AgroSciences LLC Notice of Filing Pesticide Petition #[no...
https://www.federalregister.gov/d/2017-22357 https://www.federalregister.gov/d/2017-22357
This regulation establishes tolerances for residues of fenpicoxamid (XDE 777) in or on banana, rye, and wheat. Dow AgroSciences LLC requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2016-0392, 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.
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-2016-0392 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 December 15, 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-2016-0392, by one of the following methods:
In the Federal Register of December 20, 2016 (81 FR 92758) (FRL-9956-04), 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 5E8440) by Dow AgroSciences LLC, 9330 Zionsville Rd, Indianapolis, IN 46268. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the fungicide fenpicoxamid (XDE- 777) in or on banana at 0.1 parts per million (ppm), rye, grain and wheat, grain at 0.7 ppm; and residues of fenpicoxamid and its metabolite X12326349 expressed as fenpicoxamid Start Printed Page 47997equivalents in or on meat and fat from cattle, goats, and sheep at 0.01 ppm; and meat byproducts of cattle, goats, and sheep at 0.02 ppm. That document referenced a summary of the petition prepared by Dow AgroSciences LLC, the registrant, which is available in the docket, 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 is establishing tolerances as follows: 0.15 ppm for banana and 0.60 ppm for rye, grain and wheat, grain. In addition, EPA has concluded that no tolerances are needed for livestock commodities at this time. The reason for these changes are explained in Unit IV.C.
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 fenpicoxamid including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with fenpicoxamid follows.
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. Fenpicoxamid has no significant acute toxicity via oral, dermal or inhalation route of exposure. Moreover, it is not a skin irritant and does not cause skin sensitization.
Liver effects were consistently observed in mice regardless of duration; however, the severity, magnitude, and diversity of the liver response progressed from adaptive in subchronic exposures to adverse in chronic exposures. Mice exposed to fenpicoxamid in the diet for 80 weeks experienced liver weight increase accompanied by microscopic changes including very slight to moderate centrilobular/midzonal hepatocellular hypertrophy with altered tinctorial properties (increased cytoplasmic eosinophilia), vacuolization consistent with fatty change, and very slight hepatocyte necrosis. These liver effects also coincided with an increased incidence of microscopic calculi within the gallbladder in both sexes. A treatment-related increase in liver tumors were seen in male mice and is the basis for the Agency's classification of the chemical as “Suggestive Evidence of Carcinogenic Potential”. The Agency determined that a non-linear approach adequately accounted for all chronic toxicity, including carcinogenicity, that could result from chronic exposure to fenpicoxamid and, therefore, quantification of carcinogenic potential was not required. This decision was based on the following considerations: (1) There was limited evidence of carcinogenicity in the fenpicoxamid toxicity database; (2) the concern for mutagenicity and genotoxicity is low; and (3) there was no evidence of carcinogenicity at doses at or below the chronic reference dose.
Rats were likewise only adversely affected by treatment following chronic exposures. Chronic dietary exposure elicited treatment-related changes in the kidneys (increased severity of chronic progressive glomerulonephropathy) that were considered detrimental to the rat's health. However, unlike mice, chronic exposure did not elicit an increase in neoplasms in any tissue. Rabbits and dogs tolerated oral exposure up to doses of 495 and 1,115 milligrams/kilogram/day (mg/kg/day), respectively, without any signs of deteriorating health. There was no evidence of fetal susceptibility in rats or rabbits, or offspring susceptibility in rats. None of the available studies produced evidence of treatment-induced immunotoxicity or neurotoxicity.
Specific information on the studies received and the nature of the adverse effects caused by fenpicoxamid 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 “Fenpicoxamid (XDE-777): Human Health Risk Assessment to Establish Tolerances for Bananas, Wheat, and Rye Commodities Without U.S. Registration” at pages 10 through 20 in docket ID number EPA-HQ-OPP-2016-0392.
A summary of the toxicological endpoints for fenpicoxamid used for human risk assessment is shown in the Table of this unit.Start Printed Page 47998
Table—Summary of Toxicological Doses and Endpoints for Fenpicoxamid for Use in Human Health Risk Assessments
Acute Dietary (General Population, including Infants and Children) There were no effects in the toxicity database that could be attributed to a single dose; therefore, an acute POD was not identified.
Chronic Dietary (All Populations) NOAEL = 40 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x cRfD = 0.40 mg/kg/day cPAD = 0.40 mg/kg/day Carcinogenicity study—mouse. MRID 49731126. LOAEL = 156 and 388 mg/kg/day for males and females, respectively, based on treatment-related adverse liver effects in males (increased liver weight, hypertrophy, hepatocyte necrosis and fatty change) and females (increased liver weight, hypertrophy and fatty change) and gall bladder calculi.
Cancer (oral, dermal, inhalation) “Suggestive Evidence of Carcinogenic Potential” based on the presence of liver tumors in male mice only. The cRfD is protective of carcinogenic effects.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose.
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to fenpicoxamid, EPA assessed dietary exposures from fenpicoxamid 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. No such effects were identified in the toxicological studies for fenpicoxamid; therefore, a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment, EPA used the food consumption data from the U.S. Department of Agriculture's (USDA's) 2003-2008 food consumption data from the USDA's National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA used tolerance-level residues and 100% crop treated.
iii. Cancer. As discussed in Unit III.A., EPA has concluded that a nonlinear RfD approach is appropriate for assessing cancer risk to fenpicoxamid.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residues and/or PCT information in the dietary assessment for fenpicoxamid. Tolerance-level residues and 100% CT were assumed for all food commodities.
2. Dietary exposure from drinking water. Because there are no domestic uses of fenpicoxamid registered in the United States, there will not be residues of fenpicoxamid in drinking water. Therefore, a drinking water assessment is not required.
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). Fenpicoxamid is not registered for any specific use patterns that would result in residential exposure.
EPA has not found fenpicoxamid to share a common mechanism of toxicity with any other substances, and fenpicoxamid does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that fenpicoxamid 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 at http://www.epa.gov/​pesticides/​cumulative.
2. Prenatal and postnatal sensitivity. Developmental toxicity was not observed in the rat or rabbit developmental studies and, no reproductive or offspring effects were observed in the reproduction toxicity study. As a result, EPA concluded there is low concern for prenatal or postnatal sensitivity from fenpicoxamid exposure.
3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be Start Printed Page 47999adequately protected if the FQPA SF were reduced to 1X for all exposure scenarios. That decision is based on the following findings:
i. The toxicity database for fenpicoxamid is complete.
ii. There is no indication that fenpicoxamid is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.
iii. There is no evidence that fenpicoxamid results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study.
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. Therefore, fenpicoxamid is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to fenpicoxamid from food for the highest exposed population subgroup, children 1-2 years of age, is 0.002737 mg/kg/day or <1.0% of the cPAD. The chronic dietary exposure estimate for the general population is 0.001022 mg/kg/day or <1.0% of the cPAD.
3. Short-term and intermediate-term risk. Because fenpicoxamid is not registered for any uses that may result in residential exposure, fenpicoxamid is not expected to cause any short-term or intermediate-term risk not already accounted for in the Agency's assessment of chronic risk.
4. Aggregate cancer risk for U.S. population. Based on the Agency's assessment of chronic risk, the Agency concludes that fenpicoxamid is not expected to pose a cancer risk.
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 fenpicoxamid residues.
Adequate enforcement methodology (high-performance liquid chromatography method with tandem mass spectrometry detection (LC/MS/MS), Method No. 120615) is available to enforce the tolerance expression.
Codex has not established any MRLs for residues of fenpicoxamid.
EPA is establishing tolerances for wheat, grain and rye, grain (at 0.60 ppm) that differ from what the petition requested (0.7 ppm). The petitioner included only wheat grain residues for individual growing season/area combinations. Including all residues for wheat grain in the OECD MRL calculator in accordance with Agency policy results in a tolerance level of 0.60 ppm. Because the wheat grain data can be used to assess residues in rye grain, the Agency is establishing a tolerance at 0.60 ppm for rye grain as well. Finally, although the notice of filing and the petition summary indicate that the petitioner was seeking tolerances for wheat and rye, the section of the petition that listed actual requested tolerances more narrowly sought only “wheat, grain” and “rye, grain” tolerances because those are the forms in which the wheat and rye will be imported. Accordingly, EPA is establishing tolerances for the commodities “wheat, grain” and “rye, grain”.
EPA is establishing a different tolerance level for banana than what was requested based on available residue data and the OECD calculator, and in order to harmonize with Canada's MRL.
EPA is not establishing any of the petitioned-for tolerances for livestock commodities. Based on the results of the livestock feeding studies, the residues of concern for livestock commodities (fenpicoxamid and X12326349) would be below the limit of quantification (LOQ) of the enforcement analytical method. Therefore, the Agency concludes, as indicated in 40 CFR 180.6(a)(3), that there is no reasonable expectation of finite residues and no tolerances are needed for livestock commodities at this time.
Therefore, tolerances are established for residues of fenpicoxamid and its metabolites and degradates, in or on banana at 0.15 ppm, and rye and wheat grain at 0.60 ppm.
This action establishes tolerances under FFDCA section 408(d) in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled “Regulatory Planning and Review” (58 FR 51735, October 4, 1993). Because this action has been exempted from review under Executive Order 12866, this action 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 action 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).Start Printed Page 48000
2. Add § 180.109 to subpart C to read as follows:
§ 180.109
(a) General. Tolerances are established for residues of fenpicoxamid including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels for fenpicoxamid is to be determined by measuring only fenpicoxamid ([[4-methoxy-2-[[[(3 S, 7 R, 8 R, 9 S)-9-methyl-8-(2-methyl-1-oxopropoxy)-2,6-dioxo-7-(phenylmethyl)-1,5-dioxonan-3-yl]amino]carbonyl]-3-pyridinyl]oxy]methyl 2-methylpropanoate) in or on the commodity.
Banana* 0.15
Wheat, grain* 0.60
Rye, grain* 0.60
*There are no U.S. registrations for use of fenpicoxamid on this commodity.
[FR Doc. 2017-22357 Filed 10-13-17; 8:45 am]