Source: https://www.federalregister.gov/documents/2018/05/17/2018-10582/pyroxasulfone-pesticide-tolerances
Timestamp: 2018-09-25 15:03:01
Document Index: 234408301

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

This regulation is effective May 17, 2018. Objections and requests for hearings must be received on or before July 16, 2018, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
22854-22859 (6 pages)
Acute and Chronic Aggregate (Food and Water) Dietary Exposure...
Application for Section 3 Registration for Use on Crop...
K-1 CHEMICAL U.S.A., INC Notice of Filing Pesticide Petition...
K-I CHEMICAL U.S.A., Inc. Notice of Filing Pesticide Petition...
K-I Chemical U.S.A., Inc Notice of Filing Pesticide Petition...
https://www.federalregister.gov/d/2018-10582 https://www.federalregister.gov/d/2018-10582
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2015-0787, 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.
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. Start Printed Page 22855
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-2015-0787 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 July 16, 2018. 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-2015-0787, by one of the following methods:
In the Federal Register of January 26, 2018 (83 FR 3659) (FRL-9971-46), 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 5F8521) by K-I Chemical USA, Inc., 11 Martine Ave., Suite 970, White Plains, NY 10606. The petition requested that 40 CFR part 180.659 be amended by establishing tolerances for residues of the herbicide pyroxasulfone, (3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl methylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-oxazole) in or on Crop Subgroup 1C, tuberous and corm vegetables (except granular/flakes and chips) at 0.05 parts per million (ppm); Crop Subgroup 3-07, bulb vegetables at 0.15 ppm; potatoes, granular/flakes at 0.3 ppm; and potato chips at 0.06 ppm. That document referenced a summary of the petition prepared by K-I Chemical USA, Inc., the registrant, which is available in the docket, http://www.regulations.gov. No comments were received in response to the notice of filing.
Because the January 26, 2018, document identified the K-I Chemical petition by the wrong petition number, EPA published another document in the Federal Register assigning the correct petition number to the K-I Chemical petition—PP6F8521. That document was published in the Federal Register on March 15, 2018 (83 FR 11448) (FRL-9974-72). No relevant comments were received on the notice of filing.
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.C.
The toxicology database for pyroxasulfone is adequate for evaluating and characterizing toxicity and selecting endpoints for purposes of this risk assessment. Pyroxasulfone acute toxicity to mammals is low by all routes of exposure. Subchronic and chronic oral studies in mice, rats and dogs produced a variety of effects including cardiac toxicity (increased cardiomyopathy), liver toxicity (centrilobular hepatocellular hypertrophy, histopathological and/or clinical pathological indicators), kidney toxicity (nephropathy), neurotoxicity (impaired hind limb function, ataxia, tremors, sciatic nerve lesions, axonal/myelin degeneration in the sciatic nerve and spinal cord sections), skeletal muscle myopathy, urinary bladder mucosal hyperplasia, and urinary bladder transitional cell papillomas. Minimal to mild cardiac myofiber degeneration and local inflammation were also seen in a rat dermal toxicity study. Neurotoxicity was also seen in a developmental neurotoxicity study in rats (decreased brain weight, decreased thickness of the hippocampus, corpus callosum and cerebellum in offspring). Dogs appear to be the most sensitive species to the neurotoxic effects of pyroxasulfone. Immunotoxicity studies in rats and mice show no evidence of immunotoxic effects from pyroxasulfone.
There is evidence of fetal and offspring susceptibility in the developmental neurotoxicity study in rats as effects occurred in the absence of maternal toxicity. There is no concern for reproductive toxicity. Pyroxasulfone is classified as “Not Likely to be Carcinogenic to Humans” at doses that do not cause crystals with subsequent calculi formation resulting in cellular damage of the urinary tract. The Agency has determined that the quantification Start Printed Page 22856of risk using a non-linear approach (i.e., reference dose (RfD)) will adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to pyroxasulfone.
Specific information on the studies received and the nature of the adverse effects caused by pyroxasulfone as the no-observed-adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document “Pyroxasulfone Human Health Risk Assessment for the Section 3 New Uses of Pyroxasulfone on Crop Subgroup 1C, tuberous and corm vegetables and Crop Group 3-07, bulb vegetables” at pages 39-53 in docket ID number EPA-HQ-OPP-2015-0787.
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 the NOAEL and the LOAEL are identified. 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 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 use https://www.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​assessing-human-health-risk-pesticides.
A summary of the toxicological endpoints for pyroxasulfone used for human risk assessment is shown in the Table 1 of this unit.
Table 1—Toxicological Doses and Endpoints for Pyroxasulfone for Use in Dietary Human Health Risk Assessments
RfD & PAD
Acute Dietary (General Population, including Infants and Children) NOAEL= 100 mg/kg UFA= 10x UFH=10x FQPA SF=1x Acute RfD = 1.0 mg/kg aPAD = 1.0 mg/kg 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 postnatal day (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.
Cancer (all routes) “Not Likely to be Carcinogenic to Humans” at doses that do not cause crystals with subsequent calculi formation resulting in cellular damage of the urinary tract. Risk is quantified using a non-linear (i.e., RfD) approach.
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. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Such effects were identified for pyroxasulfone. In estimating acute dietary exposure, EPA used food consumption data 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, 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 the USDA 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 classified pyroxasulfone as “Not Likely to be Carcinogenic to Humans” at doses that do not cause crystals with subsequent calculi formation resulting in cellular damage of the urinary tract. 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.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residue and PCT information in the dietary assessment for pyroxasulfone. Tolerance-level residues and 100% crop treated (CT) 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 Start Printed Page 22857account 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 at https://www.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​assessing-human-health-riskpesticides.
Based on the Pesticide Root Zone Model Ground Water (PRZM version 3.122)/Exposure Analysis Modeling System-Superseded (EXAMS version 2.98.04), the estimated concentrations of pyroxasulfone in surface water were minimal, and the highest estimated drinking water concentrations (EDWCs) of pyroxasulfone residues were from a Tier II PRZM-GW modeling at an application rate of 0.267 lbs active ingredient/Acre for registered crops. The same EDWCs have been used for the current human health dietary risk assessment. The EDWCs for peak concentration (used in the acute assessment) and 30-year average concentration (used in the chronic assessment) were 0.210 and 0.174 mg/L (ppm), respectively. Water residues were incorporated in the Dietary Exposure Evaluation Model—Food Commodity Intake Database (DEEM-FCID) into the food categories “water, direct, all sources” and “water, indirect, all sources.”
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 website at https://www.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​assessing-human-health-riskpesticides.
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 offspring at 300 mg/kg/day in the rat 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).
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:
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 DNT study. 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 identified; therefore, there is no residual uncertainty with regard to neurotoxic effects for which a 10X must be retained.
iii. Evidence of increased susceptibility of fetuses and offspring was seen in a DNT study in rats and a developmental study in rabbits following in utero or post-natal exposure to pyroxasulfone. However, no susceptibility was seen in the rat developmental or reproduction studies. 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. This increased susceptibility is occurring at high doses. NOAELs and LOAELs have been identified for all effects of concern and thus, a clear dose response has been well defined. Therefore, residual uncertainties or concerns for pre- and/or post-natal toxicity are minimal, and EPA concludes that reducing the FQPA safety factor to 1X will be protective of such effects.
iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100% CT 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 Start Printed Page 22858pyroxasulfone 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 50% of the cPAD for all infants less than 1-year old, the population group receiving the greatest exposure.
Although short-term and intermediate-term adverse effects were identified, pyroxasulfone is not registered for any use patterns that would result in residential exposure. Therefore, EPA relies on the chronic dietary risk assessment for evaluating short-term and intermediate-term risk for pyroxasulfone.
Adequate enforcement methodology (high performance liquid chromatography/triple quadrupole mass spectrometry (LC/MS/MS) methods) are available to enforce the tolerance expression.
In 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 EPA explain the reasons for departing from the Codex level. The Codex has not established a MRL for pyroxasulfone in any of the proposed commodities.
The vegetable, tuberous and corm, subgroup 1C tolerance is being established at 0.08 ppm instead of 0.05 ppm. The petitioner's requested tolerance level included only residues from the parent and M1 metabolite. The Agency is establishing this tolerance at 0.08 ppm to account for the measurement of parent and four metabolites. Applying processing factors in accordance with the Agency's policy for determining such factors when measuring multiple pesticide residues, the Agency has determined that 0.20 ppm is an appropriate tolerance level for granules/flakes. In addition, The Agency has determined that a tolerance for potato chips is not required because residues will be within the tolerance level established for subgroup 1C.
Therefore, tolerances are established for residues of pyroxasulfone including its metabolites and degradates, in or on potatoes, granules/flakes at 0.20 ppm; vegetable, bulb, group 3-07 at 0.15 ppm; and vegetable, tuberous and corm, subgroup 1C at 0.08 ppm.
This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act (NTTAA) (15 U.S.C. 272 note).Start Printed Page 22859
2. In § 180.659, add alphabetically “Potato, granules/flakes”, “Vegetable, bulb, group 3-07”, and “Vegetable, tuberous and corm, subgroup 1C” to the table in paragraph (a)(5) to read as follows:
Potato, granules/flakes 0.20
Vegetable, bulb, group 3-07 0.15
Vegetable, tuberous and corm, subgroup 1C 0.08
[FR Doc. 2018-10582 Filed 5-16-18; 8:45 am]