Source: https://www.federalregister.gov/documents/2017/05/25/2017-10765/isopyrazam-pesticide-tolerances
Timestamp: 2018-02-21 20:08:22
Document Index: 168988556

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

This regulation is effective May 25, 2017. Objections and requests for hearings must be received on or before July 24, 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).
82 FR 24071
24071-24076 (6 pages)
EPA-HQ-OPP-2016-0143
FRL-9960-76
Isopyrazam. Tolerances with No U.S. Registrations in/on...
Revised Section F Proposed New Tolerance for The Pesticide...
https://www.federalregister.gov/d/2017-10765 https://www.federalregister.gov/d/2017-10765
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2016-0143, 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-2016-0143 in the subject line on the first page of your submission. All Start Printed Page 24072objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before July 24, 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-2016-0143, by one of the following methods:
In the Federal Register of August 29, 2016 (81 FR 59165) (FRL-9950-22), 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 5E8433) by Syngenta Crop Protection, LLC, 410 Swing Road, P.O. Box 18300, Greensboro, NC 27419. The petition requested that 40 CFR 180.654 be amended by establishing tolerances for residues of the fungicide isopyrazam, in or on cucurbit crop subgroup 9A at 0.3 parts per million (ppm); pepper, bell at 0.6 ppm; and tomato at 0.5 ppm. That document referenced a summary of the petition prepared by Syngenta Crop Protection, 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 a lower tolerance than was requested for pepper, bell and is revising the commodity terminology for vegetable, cucurbit, subgroup 9A. The reasons 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 isopyrazam including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with isopyrazam follows.
Subchronic and chronic oral toxicity studies in the rat, mouse, rabbit and dog demonstrate that the primary target organ for isopyrazam is the liver (increased organ weight and centrilobular hepatocyte hypertrophy). Liver toxicity is usually accompanied by reductions in bodyweight and food consumption. Isopyrazam did not cause reproductive toxicity. Effects seen in the offspring (decreased bodyweight during lactation and increase liver weight at weaning) in the rat reproduction study occurred at the same doses that cause general toxicity in the parents. Developmental effects described as small eyes and/or microphthalmia were observed in both the Himalayan and New Zealand rabbit strains. However, in the Himalayan strain, the intraocular abnormalities occur in the absence of maternal toxicity while in the New Zealand strain, the ocular abnormalities occurred at doses that were maternally toxic. Developmental effects observed in the rat (increased post-implantation loss, reduced fetal weight, and a non- or incomplete ossification or retardation of ossification) occurred at doses that also produced maternal toxicity (mortality, decreased body weights, body weight gains, and food consumption, increased liver weights and microscopic findings in the liver).
No evidence of specific neurotoxicity was seen in acute and subchronic oral neurotoxicity studies in rats. Clinical signs seen in two subchronic dog studies (side-to-side head wobble, ataxia, reduced stability) are consistent with neurotoxic effects. However, detailed and specific neuropathological analyses were not conducted for the dog studies (i.e., functional observational battery, motor activity, detailed histopathology with special stains). Consequently, there is uncertainty regarding whether the effects seen in the dog studies are in fact signs of neurotoxicity. However, clear no observed adverse effect levels (NOAELs)/lowest adverse effect levels (LOAELs) were established for both subchronic dog studies. The point of departure selected for the acute dietary assessment is based on clinical signs seen on day 2 in one of four males in the subchronic dog study. This study provides the lowest NOAEL in the database (most sensitive endpoint) for a single dose effect. The dose used for the chronic dietary risk assessment is eight times lower than the dose at which clinical effects were seen at four weeks in the second subchronic dog study.
There is no evidence of immunotoxicity based on a 28-day dietary immunotoxicity study in mice. The LOAEL for immunotoxicity was not identified and the NOAEL for immunotoxicity was 1,356 milligrams/kilograms (mg/kg).
Isopyrazam is classified as “Likely to be Carcinogenic to Humans” based on increased incidence of uterine endometrial adenocarcinomas and liver hepatocellular adenomas in female rats and increased incidence of thyroid follicular cell adenomas and/or Start Printed Page 24073carcinomas in male rats. Isopyrazam is not carcinogenic in the mouse. There is no evidence of genotoxicity, mutagenicity, or clastogenicity in the in vivo and in vitro studies. There are no structural relationships with other known carcinogens. A linear low-dose approach (Q1*) was used to extrapolate experimental animal tumor data for the quantification of human cancer risk.
Isopyrazam is of low acute toxicity by the oral, dermal, and inhalation routes and is not a skin or eye irritant.
Specific information on the studies received and the nature of the adverse effects caused by isopyrazam 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 “Isopyrazam: Human Health Risk Assessment for the Establishment of Tolerances with No U.S. Registrations in/on Cucurbit Vegetables Crop Subgroup 9A, Bell Pepper and Tomato Imported from Belgium, Greece, Italy, Spain and the United Kingdom” in docket ID number EPA-HQ-OPP-2016-0143.
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://www2.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​assessing-human-health-risk-pesticides. A summary of the toxicological endpoints for isopyrazam used for human risk assessment is discussed in Table 1 of the final rule published in the Federal Register of December 27, 2013 (78 FR 78740) (FRL-9903-53).
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to isopyrazam, EPA considered exposure under the petitioned-for tolerances as well as all existing isopyrazam tolerances in 40 CFR 180.654. EPA assessed dietary exposures from isopyrazam 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 isopyrazam. In estimating acute dietary exposure, EPA used food consumption information from the United States Department of Agriculture (USDA) 2003-2008 National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, maximum residues from field trials conducted at the maximum use rates were used to estimate isopyrazam residues of concern and 100 percent crop treated (PCT) assumptions were used. Dietary Exposure Evaluation Model (DEEM) default processing factors were used for all processed commodities including dried apple (8.0), apple juice/cider (1.3), dried banana/plantain (3.9), peanut butter (1.89), dried tomato (14.3), tomato juice (1.5), tomato paste (5.4), and tomato puree (3.3). In the absence of peanut processing data, the maximum theoretical concentration factor was used for peanut oil (2.8).
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 2003-2008 NHANES/WWEIA. As to residue levels in food, EPA used the average residues from field trials conducted at the maximum use rates were used to estimate isopyrazam and the same processing factors and PCT assumptions as in the acute dietary exposure analysis.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that isopyrazam should be classified as “Likely to be Carcinogenic to Humans” and a linear approach has been used to quantify cancer risk. In evaluating the cancer risk, EPA used the same residue levels, processing factors and PCT assumptions as in the chronic dietary exposure analysis.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use PCT information in the dietary assessment for isopyrazam. Maximum or average residue levels from field trials conducted at the maximum use rates were assumed for all food commodities.
2. Dietary exposure from drinking water. An assessment of residues in drinking water is not needed for isopyrazam because there is no drinking water exposure for isopyrazam uses, which are all non-domestic.
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). Isopyrazam 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 substances that have a common mechanism of toxicity.” EPA has not found isopyrazam to share a common mechanism of toxicity with any other substances, and isopyrazam does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that isopyrazam does not have a common mechanism of toxicity with other substances. For information regarding EPA's procedures for cumulating effects from substances found to have a common mechanism of toxicity, see EPA's Web site at http://www2.epa.gov/​Start Printed Page 24074pesticide-science-and-assessing-pesticide-risks/​cumulative-assessment-risk-pesticides.
2. Prenatal and postnatal sensitivity. There are no residual uncertainties for pre- and/or postnatal susceptibility even though qualitative susceptibility was observed in the range-finding developmental studies in rabbits. Developmental effects (eye abnormalities) were observed in the absence of maternal toxicity in two range finding developmental toxicity studies in the Himalayan rabbit. However, the eye effects were only observed at relatively high doses (200-400 mg/kg/day) with clear NOAELs/LOAELs established for the developmental effects. Developmental effects observed in the rat (increased post-implantation loss, reduced fetal weight and non-or incomplete ossification or retardation of ossification) occurred only at doses that also produced maternal toxicity (mortality, decreased body weights, body weight gains, and food consumption). There was no evidence of increased susceptibility in a 2-generation reproduction study following pre- or postnatal exposure to isopyrazam. There was also no evidence of neuropathology or abnormalities in the development of the fetal nervous system from the available toxicity studies conducted with isopyrazam. Clear NOAELs/LOAELs were established for the developmental effects observed in rats and rabbits as well as for the offspring effects (increased liver weights) seen in the 2-generation reproduction study and a dose-response relationship for the effects of concern is well characterized. The dose used for the acute dietary risk assessment (30 mg/kg/day), based on effects seen in the subchronic dog study, is protective of the developmental effects seen in rats (44.5 mg/kg/day) and rabbits (200 mg/kg/day). Based on these considerations, there are no residual uncertainties for pre- and/or postnatal susceptibility.
i. The toxicity database for isopyrazam is complete.
ii. As discussed in Unit III.A, there is no indication that isopyrazam is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional uncertainty factors to account for neurotoxicity.
iii. As discussed in Unit III.D.2, there are no residual uncertainties for pre-and/or post-natal susceptibility.
iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100 PCT and maximum or average residue levels from field trials conducted at the maximum use rates. There are no currently registered or proposed occupational or residential uses of isopyrazam in the U.S. and adequate residue data are available. These assessments will not underestimate the exposure and risks posed by isopyrazam.
1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food to isopyrazam at the 95th percentile will occupy 4.7% 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 isopyrazam from food will utilize 5.0% of the cPAD for children 1-2 years old, the population group receiving the greatest exposure. There are no residential uses for isopyrazam.
3. Short- and intermediate-term risk. Short- and intermediate-term risk is assessed based on short- and intermediate-term residential exposure plus chronic dietary exposure (which includes both food and water and is considered to be a background exposure level). Isopyrazam is not registered in the United States. Because there is no short- or intermediate-term residential exposure and chronic dietary exposure has already been assessed under the appropriately protective cPAD, no further assessment of short- or intermediate-term risk is necessary, and EPA relies on the chronic dietary risk assessment for evaluating short- and intermediate-term risk for isopyrazam.
4. Aggregate cancer risk for U.S. population. Using the exposure assumptions discussed in this unit for cancer exposure, the cancer dietary risk estimate for the U.S. population is 3 × 10−6. EPA generally considers cancer risks (expressed as the probability of an increased cancer case) in the range of 1 in 1 million (or 1 × 10−6) or less to be negligible. The precision that can be assumed for cancer risk estimates is best described by rounding to the nearest integral order of magnitude on the logarithmic scale; for example, risks falling between 3 × 10−7 and 3 × 10−6 are expressed as risks in the range of 10−6. Considering the precision with which cancer hazard can be estimated, the conservativeness of low-dose linear extrapolation, and the rounding procedure described above, cancer risk should generally not be assumed to exceed the benchmark level of concern of the range of 10−6 until the calculated risk exceeds approximately 3 × 10−6. This is particularly the case where some conservatism is maintained in the exposure assessment. For isopyrazam, EPA's exposure assessment assumes average residues of concern from field trials reflecting the maximum use rates, default processing factors, the maximum theoretical concentration for residues in peanut oil, and 100 PCT, which is highly conservative. Accordingly, EPA has concluded the cancer risk from exposure to isopyrazam falls within the range of 10−6 and is thus negligible.
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 isopyrazam residues.
Adequate enforcement methodology (GRM006.01B) is available to enforce Start Printed Page 24075the 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.
The Codex has not established MRLs for isopyrazam in or on vegetable, cucurbit, subgroup 9A; pepper, bell; and tomato.
Based on the residue levels observed in the field trial studies, EPA is establishing a tolerance of 0.50 ppm in or on pepper, bell in lieu of the 0.6 ppm as requested by the petitioner. The tolerance requested for Cucurbit Crop Group 9A is also being established as Vegetable, cucurbit, subgroup 9A, which is the standard commodity description for these commodities. The petitioned-for tolerances for residues of isopyrazam in/on cucurbit crop group 9A (0.3 ppm) and tomato (0.5 ppm) are set at 0.30 ppm and 0.50 ppm, respectively, consistent with the current practices for setting tolerances.
Therefore, tolerances are established for residues of isopyrazam, (3-(difluoromethyl)-1-methyl-N-[1,2,3,4-tetrahydro-9-(1-methylethyl)-1,4-methano-naphthalen-5-yl]-1 H-pyrazole-4-carboxamide), determined as the sum of its syn-isomer (3-(difluoromethyl)-1-methyl-N-[(1RS, 4SR, 9RS)-1,2,3,4-tetrahydro-9-(1-methylethyl)-1,4-methanonaphthalen-5-yl]-1 H-pyrazole-4-carboxamide) and anti-isomer (3-(difluoromethyl)-1-methyl-N-[(1RS, 4SR, 9SR)-1,2,3,4-tetrahydro-9-(1-methylethyl)-1,4-methano-naphthalen-5-yl]-1 H-pyrazole-4-carboxamide), in or on vegetable, cucurbit, subgroup 9A at 0.30 ppm; pepper, bell at 0.50 ppm; and tomato at 0.50 ppm.
2. In § 180.654, add alphabetically the entries “Pepper, bell”, “Tomato”, and “Vegetable, cucurbit, subgroup 9A” to the table in paragraph (a), and revise footnote 1 at the end of the table to read as follows:
§ 180.654
Pepper, bell 1 0.50
Tomato 1 0.50
Vegetable, cucurbit, subgroup 9A 1 0.30
1 There are no U.S. registrations for use of isopyrazam on these commodities.
[FR Doc. 2017-10765 Filed 5-24-17; 8:45 am]