Source: https://www.federalregister.gov/documents/2017/04/18/2017-07819/pyroxasulfone-pesticide-tolerances
Timestamp: 2018-02-25 14:38:26
Document Index: 280389710

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

18230-18235 (6 pages)
EPA-HQ-OPP-2016-0171
FRL-9959-25
Pyroxasulfone Human Health Risk Assessment for the Section 3...
Drinking Water Assessment of Pyroxasulfone Proposed Use on...
Pyroxasulfone. Application for Section 3 Registration for Use...
Pyroxasulfone. Acute and Chronic Aggregate (Food and Water)...
https://www.federalregister.gov/d/2017-07819 https://www.federalregister.gov/d/2017-07819
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2016-0171, 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-2016-0171 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 June 19, 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-2016-0171, by one of the following methods:
In the Federal Register of May 19, 2016 (81 FR 31581) (FRL-9946-02), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. Start Printed Page 18231346a(d)(3), announcing the filing of a pesticide petition (PP 6E8454) by IR-4, Rutgers University, 500 College Rd. East, Suite 201 W, Princeton, NJ 08540. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of pyroxasulfone (3-[[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1 H-pyrazol-4-yl]methyl]sulfonyl]-4,5-dihydro-5,5-dimethylisoxazole) and its metabolites (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1 H-pyrazol-4- carboxylic acid (M-3); 5-(difluoromethoxy)-3-(trifluoromethyl)-1 H-pyrazol-4-yl]methanesulfonic acid (M-25); 3-[1-carboxy-2-(5,5-dimethyl-4,5-dihydroisoxazol-3-ylthio)ethylamino]-3-oxopropanoic acid (M-28); and 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1 H-pyrazol-4-yl]methanesulfonic acid (M-1)) calculated as the stoichiometric equivalent of pyroxasulfone in or on the raw agricultural commodity sunflower subgroup 20B at 0.2 parts per million. That document referenced a summary of the petition prepared by K-I Chemical U.S.A. Inc., the registrant, which is available in the docket, http://www.regulations.gov. A comment supporting IR-4's petition requesting this tolerance was received in response to the notice of filing.
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 5F8417) by K-I Chemical USA. Inc., 11 Martine Ave., Suite 970, White Plains, NY 10606. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the herbicide, pyroxasulfone (3-[(5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl) pyrazole-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-oxazole) and its metabolites in or on dried shelled peas and beans (crop subgroup 6C) at 0.15 ppm, pea hay at 0.40 ppm, pea vines at 0.20 ppm, cowpea hay at 0.07 ppm, cowpea forage at 3.0 ppm, flax at 0.07 ppm, peanut at 0.20 ppm, peanut hay at 3.0 ppm, peanut meal at 0.40 ppm, and vegetable, foliage of legume, except soybean, subgroup 7A at 3.0 ppm. That document referenced a summary of the petition prepared by K-I Chemical U.S.A. Inc., the registrant, which is available in docket number EPA-HQ-OPP-2015-0787, http://www.regulations.gov.
The December 20, 2016 notice of filing supersedes a notice of filing published in the Federal Register of June 22, 2016 (81 FR 40594) (FRL-9947-32), which was based on an earlier version of the same petition (5F8417). Following that June 2016 publication, K-1 amended its petition to include additional crops and adjust the tolerance levels requested. The December 20, 2016 document provided notice of that updated petition. Although no comments were received in response to the December 20, 2016 notice of filing, one comment was received in response to the June 22, 2016 notice. EPA is carrying that earlier comment forward as a comment on the petition noticed in December 2016 and provides a response to that comment in Unit IV.C.
Based upon review of the data supporting the petition, EPA has modified the levels at which some of the tolerances are being established and also modified some of the crop definitions. The reasons for these changes are explained in Unit IV.D.
Subchronic and chronic toxicity testing of pyroxasulfone in mice, rats and dogs produced a variety of adverse effects in several target organs, but the most sensitive effect is neurotoxicity in dogs. Effects seen in animal studies ranged from cardiac toxicity (increased cardiomyopathy in mice and rats), liver toxicity (centrilobular hepatocellular hypertrophy, histopathological and/or clinical pathological indicators), neurotoxicity characterized by axonal/myelin degeneration in the sciatic nerve (dog, mouse and rat) and spinal cord sections (dog), skeletal muscle myopathy, kidney toxicity (increased incidence of chronic progressive nephropathy in dogs and retrograde nephropathy in mice), urinary bladder mucosal hyperplasia, inflammation, and urinary bladder transitional cell papillomas (rats). Decreased body weight and enzyme changes were noted in some studies. Toxic adverse effects (impaired hind limb function, ataxia, hind limb twitching and tremors; increased creatine kinase, aspartate aminotransferase; axonal/myelin degeneration of the sciatic nerve and spinal cord sections) in dogs occurred at ≥10 mg/kg/day doses while in the mouse toxic adverse effects (degeneration of sciatic and trigeminal nerve axons and their associated myelin sheaths and chronic progressive nephropathy, renal tubular adenomas) occurred at higher doses (131 mg/kg/day and above).
Comparing effects by route of administration, pyroxasulfone was moderately toxic to rats following a 4-week dermal exposure producing local inflammation and systemic effects of minimal to mild cardiac myofiber degeneration at the limit dose of 1,000 mg/kg/day with a NOAEL of 100 mg/kg/day. No adverse effects were noted in an inhalation study following exposure for 28 days at 200 mg/m3/day (equivalent to 52.2 mg/kg/day oral dose), the highest dose tested of an aerosol dust.
In cancer studies in mice and rats, renal tubular adenomas were observed in male mice at a dietary dose of 0.6 and 255 mg/kg/day (but not at an intermediate dose of 18 mg/kg/day) and urinary bladder transitional cell papillomas were observed in male rats at 42 and 84 mg/kg/day. Based on available information, the Agency concluded that the kidney adenomas in male mice were not treatment-related. Start Printed Page 18232The Agency considered the transitional cell bladder tumors in male rats to be treatment-related based on statistically significant trends for urinary bladder transitional cell papillomas and combined papillomas and carcinomas, the occurrence of preneoplastic lesions at 42 and 84 mg/kg/day and the rare occurrence of bladder transitional cell tumors. The Agency concluded that the mode of action for bladder tumors has been adequately established based on submitted data that support both a dose-response and temporal concordance of the key events and bladder tumors. The available data indicate that the formation of urinary bladder calculi is the prerequisite for subsequent hyperplasia and neoplasia and that tumors do not develop at doses too low to produce calculi. The Agency has determined that the quantification of risk using a non-linear approach (i.e., RfD) will adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to pyroxasulfone. There is a clear threshold of 1,000 ppm (42.55 mg/kg/day) for tumorigenesis. A point of departure (POD) of 50 ppm (2.0 mg/kg/day) is not expected to result in urinary bladder calculi formation which is a prerequisite for subsequent hyperplasia and neoplasia.
Pyroxasulfone did not exhibit developmental toxicity in the rat developmental toxicity study at the limit dose of 1,000 mg/kg/day and it exhibited slight developmental toxicity in rabbits (reduced fetal weight and resorptions) at the limit dose of 1,000 mg/kg/day. However, developmental effects were noted in post-natal day (PND) 21 offspring at 300 mg/kg/day in the rat developmental neurotoxicity (DNT) study characterized as decreased brain weight and morphometric changes. Developmental effects in the rabbit developmental study and DNT study occurred in the absence of maternal toxicity, indicating potential increased quantitative susceptibility of offspring. In a reproductive toxicity in rats reduced pup weight and body weight gains during lactation occurred at similar doses causing pronounced maternal toxicity (reduced body weight, body weight gain and food consumption and increased kidney weight, cardiomyopathy and urinary bladder mucosal hyperplasia with inflammation).
Pyroxasulfone did not produce immunotoxic effects in mice following dietary feeding for 28 days up to 4,000 ppm (633/791 mg/kg/day, M/F) or in rats at dietary concentrations of 7,500 ppm (529/570 mg/kg/day in M/F).
Specific information on the studies received and the nature of the adverse effects caused by pyroxasulfone 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 the document title “Pyroxasulfone Human Health Risk Assessment for the Section 3 New Uses of Pyroxasulfone on Crop Subgroup 6C, Sunflower Subgroup 20B, Flax, and Peanut” on page 44 in docket ID number EPA-HQ-OPP-2016-0171.
Acute dietary (General population including infants and children) 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 neurotoxicity study (DNT) in rats. The LOAEL of 300 mg/kg/day is based on decreased brain weight in both sexes, reduced thickness of the hippocampus, corpus callosum and cerebellum in PND 21 female offspring.
Chronic dietary (All populations) NOAEL = 2 mg/kg/day UFA = 10x UFH = 10x FQPA SF = 1x Chronic RfD = 0.02 mg/kg/day cPAD = 0.02 mg/kg/day One- year chronic dog study. The LOAEL of 10 mg/kg/day is based on impaired hind limb function, ataxia, hind limb twitching and tremors; clinical pathology: Increased creatine kinase, aspartate aminotransferase; axonal/myelin degeneration of the sciatic nerve and spinal cord sections.
Start Printed Page 18233
Such effects were identified for pyroxasulfone. In estimating acute dietary exposure, EPA used food consumption information from the United States Department of Agriculture's (USDA) 2003-2008 National Health and Nutrition Survey/What We Eat in America (NHANES/WWEIA). As to residue levels in food, EPA assumed 100 percent crop treated (PCT) and tolerance level residues adjusted for metabolites which are not in the tolerance expression.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from USDA's 2003-2008 NHANES/WWEIA. As to residue levels in food, EPA assumed 100 PCT and tolerance level residues adjusted for metabolites which are not in the tolerance expression.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that a nonlinear RfD approach is appropriate for assessing cancer risk to pyroxasulfone. Cancer risk was assessed using the same exposure estimates as discussed in Unit III.C.1.ii., chronic exposure.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residue or PCT information in the dietary assessment for pyroxasulfone. Tolerance level residues and 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for pyroxasulfone in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of pyroxasulfone. 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 Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) and Pesticide Root Zone Model Ground Water (PRZM GW), the estimated drinking water concentrations (EDWCs) of pyroxasulfone for acute exposures are estimated to be 16.7 parts per billion (ppb) for surface water and 210 ppb for ground water. EDWCs of pyroxasulfone for chronic exposures for non-cancer assessments are estimated to be 4.5 ppb for surface water and 174 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For the acute dietary risk assessment, the water concentration value of 210 ppb was used to assess the contribution to drinking water. For the chronic dietary risk assessment, the water concentration value of 174 ppb was used to assess the contribution to drinking water.
Pyroxasulfone is not registered for any specific use patterns that would result in residential exposure.
EPA has not found pyroxasulfone to share a common mechanism of toxicity with any other substances, and pyroxasulfone does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that pyroxasulfone 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://www2.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​cumulative-assessment-risk-pesticides.
2. Prenatal and postnatal sensitivity. Pyroxasulfone did not exhibit developmental toxicity in the rat guideline study at the limit dose of 1,000 mg/kg/day and it exhibited slight developmental toxicity in rabbits (reduced fetal weight and resorptions) at the limit dose of 1,000 mg/kg/day. However, developmental effects were noted in PND 21 offspring at 300 mg/kg/day in the rat developmental neurotoxicity (DNT) study characterized as decreased brain weight and morphometric changes. Developmental effects in the rabbit developmental study and DNT study occurred in the absence of maternal toxicity, indicating potential increased quantitative susceptibility of offspring. In a rat reproductive toxicity study, reduced pup weight and body weight gains during lactation occurred at similar doses causing pronounced maternal toxicity (reduced body weight, body weight gain and food consumption and increased kidney weight, cardiomyopathy and urinary bladder mucosal hyperplasia with inflammation).
ii. Available data indicates that pyroxasulfone produces neurotoxic effects in rats. The toxicity database includes specific acute and subchronic neurotoxicity tests, as well as a developmental neurotoxicity study (DNT). Although the DNT indicated offspring are more sensitive to neurotoxic effects of pyroxasulfone, the dose-response is well characterized for neurotoxicity and a NOAEL is Start Printed Page 18234identified; therefore, there is no residual uncertainty with regard to neurotoxic effects for which a 10X must be retained.
iii. As discussed in Unit III.D.2., there is evidence of increased quantitative susceptibility of fetuses and offspring following in utero or post-natal exposure to pyroxasulfone (based on a DNT study in rats and a developmental study in rabbits). In rabbits, developmental toxicity was only seen at the limit dose of 1000 mg/kg/day as reduced fetal weight and increased fetal resorptions with a NOAEL of 500 mg/kg/day for these effects, compared to no maternal toxicity at these doses. In a DNT study in rats, offspring toxicity was seen at 300 mg/kg/day compared to no maternal toxicity at 900 mg/kg/day. Notwithstanding, the Agency concludes that there is no residual uncertainty concerning these effects. The available studies show clear NOAELs and LOAELs for these effects, which are occurring only at doses much higher than the endpoints on which the Agency is regulating.
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 pyroxasulfone in drinking water. These assessments will not underestimate the exposure and risks posed by pyroxasulfone.
1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to pyroxasulfone will occupy 3.7% of the aPAD for all infants less than 1-year-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 pyroxasulfone from food and water will utilize 49% of the cPAD for all infants less than 1-year-old, the population group receiving the greatest exposure. There are no residential uses for pyroxasulfone.
Short- and intermediate-term adverse effects were identified; however, pyroxasulfone is not registered for any use patterns that would result in short- or intermediate-term residential exposure. Short- and intermediate-term risk is assessed based on short- and intermediate-term residential exposure plus chronic dietary exposure. Because there is no short- or intermediate-term residential exposure 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-term risk), 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 pyroxasulfone.
Adequate enforcement methodology (high performance liquid chromatography/triple quadrupole mass spectrometry (LC/MS/MS)) is available to enforce the tolerance expression.
The Codex has not established any MRLs for residues of pyroxasulfone in or on any of the commodities in this document.
One comment was received in response to the June 22, 2016 Notice of Filing (81 FR 40594) (FRL-9947-32). The comment stated in part that most Americans “don't need or want more toxic chemicals” and that EPA should deny this submission. The Agency recognizes that some individuals believe that pesticides should be banned on agricultural crops. However, the existing legal framework provided by section 408 of the FFDCA states that tolerances may be set when persons seeking such tolerances or exemptions have demonstrated that the pesticide meets the safety standard imposed by that statute. The citizen's comment does not provide any information upon which the Agency could base a decision deny the petition.
The sunflower subgroup 20B tolerance is being established at 0.30 ppm instead of the proposed level of 0.2 ppm. This is because the petitioner did not convert the metabolites to parent equivalents and when those total residues are put into the tolerance calculator the correct value is 0.30 ppm. Also, based on the Agency's review of the residue data, the tolerances for peanut and peanut hay are being established at 0.30 ppm and 4.0 ppm, respectively. In addition, separate tolerances are not being established on field pea hay and vines and cowpea hay Start Printed Page 18235and forage because they will be covered by the tolerance being established on “vegetable, foliage of legume, except soybean, subgroup 7A.”
Therefore, tolerances are established for residues of pyroxasulfone, including its metabolites and degradates, in or on: Flax, seed at 0.07 ppm; pea and bean, dried shelled, except soybean, subgroup 6C at 0.15 ppm; peanut at 0.30 ppm; peanut, hay at 4.0 ppm; peanut, meal at 0.40 ppm; sunflower subgroup 20B at 0.30 ppm; and vegetable, foliage of legume, except soybean, subgroup 7A at 3.0 ppm.
Dated: February 24, 2017,
2. In § 180.659, add paragraph (a)(5) to read as follows:
(5) Tolerances are established for residues of the herbicide pyroxasulfone, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of pyroxasulfone (3-[(5-difluoromethoxy-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-oxazole), and its metabolites, M-1 (5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl) methanesulfonic acid), M-3 (5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid), M-25 (5-difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-yl)methanesulfonic acid) and M-28 (3-[1-carboxy-2-(5,5-dimethyl-4,5-dihydroisoxazol-3-ylthio)ethylamino]-3-oxopropanoic acid) calculated as the stoichiometric equivalent of pyroxasulfone, in or on the following commodities:
Flax, seed 0.07
Peanut 0.30
Sunflower subgroup 20B 0.30
Vegetable, foliage of legume, except soybean, subgroup 7A 3.0
[FR Doc. 2017-07819 Filed 4-17-17; 8:45 am]