Fluxapyroxad; Pesticide Tolerances
Federal Register, Volume 81 Issue 87 (Thursday, May 5, 2016)
Federal Register Volume 81, Number 87 (Thursday, May 5, 2016)
Rules and Regulations
Pages 27019-27025
From the Federal Register Online via the Government Publishing Office www.gpo.gov
FR Doc No: 2016-10581
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
EPA-HQ-OPP-2015-0324; FRL-9945-48
Fluxapyroxad; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of fluxapyroxad in or on multiple commodities which are identified and discussed later in this document. BASF Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective May 5, 2016. Objections and requests for hearings must be received on or before July 5, 2016, 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-2015-0324, 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: Susan Lewis, 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:
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General Information
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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).
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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. To access the OCSPP test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp and select ``Test Methods and Guidelines.''
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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-2015-0324 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 5, 2016. 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-2015-0324, 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
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follow the instructions at http://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.
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Summary of Petitioned-for Tolerance
In the Federal Register of August 26, 2015 (80 FR 51759) (FRL-9931-
74), 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 5F8344) by BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709. The petition requested that 40 CFR 180.666 be amended by establishing tolerances for residues of the fungicide fluxapyroxad, in or on citrus, dried pulp at 2.7 parts per million (ppm); citrus oil at 19 ppm; fruit, citrus group 10-10 at 1.0 ppm; grass forage, fodder and hay group 17 at 30 ppm; non-grass animal feed, group 18 at 30 ppm; and poultry, fat at 0.005 ppm. The petition also requested that the existing tolerance for residues of fluxapyroxad on egg be amended from 0.002 ppm to 0.01 ppm and that the tolerance for inadvertent residues of fluxapyroxad on nongrass animal feeds, group 18 at 0.3 ppm be removed upon establishment of the superceding group 18 tolerance. That document referenced a summary of the petition prepared by BASF Corporation, 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 has recommended tolerances for poultry meat, poultry meat byproduct, and milk fat for which there were no established tolerances previously due to low dietary burden and falling under category 3 of CFR 180.6(a). The reason for these changes are explained in Unit IV.D.
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Aggregate Risk Assessment and Determination of Safety
Section 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.* * *''
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 fluxapyroxad including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with fluxapyroxad follows.
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Toxicological Profile
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.
Fluxapyroxad is of low acute toxicity by the oral, dermal and inhalation routes, is not irritating to the eyes and skin, and is not a dermal sensitizer. The primary target organ for fluxapyroxad exposure via the oral route is the liver with secondary toxicity in the thyroid for rats only. Liver toxicity was observed in rats, mice, and dogs, with rats as the most sensitive species for all durations of exposure. In rats, adaptive effects of hepatocellular hypertrophy and increased liver weights and changes in liver enzyme activities were first observed. As the dose or duration of exposure to fluxapyroxad increased, clinical chemistry changes related to liver function also occurred, followed by hepatocellular necrosis, neoplastic changes in the liver, and tumors. Thyroid effects were observed only in rats. These effects were secondary to changes in liver enzyme regulation, which increased metabolism of thyroid hormone, resulting in changes in thyroid hormones, thyroid follicular hypertrophy and hyperplasia, and thyroid tumor formation. Tumors were not observed in species other than rats or in organs other than the liver and thyroid.
Fluxapyroxad is classified as ``Not likely to be Carcinogenic to Humans'' based on convincing evidence that carcinogenic effects are not likely below a defined dose range. There is no mutagenicity concern from in vivo or in vitro assays. The hypothesized mode of action (i.e., a non-genotoxic) for treatment related tumors (i.e., the liver and thyroid) was supported by a full panel of in vitro and in vivo studies that showed no evidence of genotoxicity, together with mechanistic studies in the liver and thyroid of rats that satisfied stringent criteria for establishing tumorigenic modes of action. The studies clearly identified the sequence of key events, dose-response concordance and temporal relationship to the tumor types. The Agency has determined that the chronic population adjusted dose (PAD) will adequately account for all chronic effects, including carcinogenicity that could result from exposure to fluxapyroxad because the points of departure (POD) for the chronic population adjusted dose (cPAD) is based on the most sensitive endpoint, liver effects. Effects in the liver preceded liver tumors and the effects observed in the thyroid (in rats only) were believed to be secondary to the liver effects.
No evidence of neurotoxicity was observed in response to repeated administration of fluxapyroxad. An acute neurotoxicity study showed decreased rearing and motor activity. This occurred on the day of dosing only and in the absence of histopathological effects or alterations in brain weights. This indicated that any neurotoxic effects of fluxapyroxad are likely to be transient and reversible due to alterations in neuropharmacology and not from neuronal damage. There were no neurotoxic effects observed in the subchronic dietary toxicity study. No evidence of reproductive toxicity was observed. Developmental effects observed in both rats and mice (thyroid follicular hypertrophy and hyperplasia in rats and decreased defecation, food consumption, body weight/body weight gain, and increased litter loss in rabbits) occurred at the same doses as those that caused adverse effects in maternal animals, indicating no quantitative susceptibility. Since the maternal toxicities of thyroid hormone perturbation in rats and systemic toxicity in rabbits likely contributed to the observed developmental effects there is low concern for qualitative susceptibility. An immunotoxicity study in mice showed no evidence of immunotoxic effects from fluxapyroxad.
Subchronic oral toxicity studies in rats, developmental toxicity studies in rabbits, and in vitro and in vivo genotoxicity studies were performed for fluxapyroxad metabolites F700F001, M700F002, and M700F048. Like
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fluxapyroxad, no genotoxic effects were observed for any of these metabolites. All three metabolites displayed lower subchronic toxicity via the oral route than fluxapyroxad, with evidence of non-specific toxicity (decreased body weight) observed only for M700F0048 at the limit dose. Only M700F0048 exhibited developmental toxicity at doses similar to those that caused developmental effects in rabbits with fluxapyroxad treatment. However, these effects (abortions and resorptions) were of a different nature than for fluxapyroxad (paw hyperflexion) and are considered secondary to maternal toxicity. The Agency considers these studies sufficient for hazard identification and characterization and concludes that these metabolites do not have hazards that exceed those of fluxapyroxad in nature, severity, or potency.
Specific information on the studies received and the nature of the adverse effects caused by fluxapyroxad 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, ``Human Health Risk Assessment for Use of Fluxaproxad on Citrus Crop Group 10-10, Grass Crop Group 17, and Non-Grass Crop Group 18.'' on pp. 56 in docket ID number EPA-HQ-OPP-
2012-0638.
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Toxicological Points of Departure/Levels of Concern
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://www.epa.gov/pesticides/factsheets/riskassess.htm.
Summary of the toxicological endpoints for used for human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Fluxapyroxad for Use in Dietary, Residential and Non-
Occupational Human Health Risk Assessments
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Uncertainty/ RfD, PAD, level
Exposure/scenario Point of FQPA safety of concern for Study and toxicological
departure factors risk assessment effects
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Acute Dietary (General NOAEL = 125 mg/ UFA = 10x Acute RfD = Acute neurotoxicity study in
Population, including kg/day. UFH = 10x...... 1.25 mg/kg/day. rats.
Infants and Children and FQPA SF = 1x... aPAD = 1.25 mg/ LOAEL = 500 mg/kg/day based on
Females 13-49 years of age). kg/day. decreased motor activity
(both sexes) and decreased
rearing (males only).
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Chronic Dietary (All NOAEL = 2.1 mg/ UFA = 10x Chronic RfD = Chronic toxicity/
Populations). kg/day. UFH = 10x...... 0.021 mg/kg/ carcinogenicity study in
FQPA SF = 1x... day. rats.
cPAD = 0.021 mg/ LOAEL = 11 mg/kg/day based on
kg/day. non-neoplastic changes in the
liver (foci, masses).
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Incidental Oral Short-Term (1- NOAEL = 7.3mg/ UFA = 10x Residential LOC 90-day dietary study in rats.
30 days). kg/day. UFH = 10x...... for MOE = 100. MIRD 47923567.
FQPA SF = 1x... LOAEL = 35.1 mg/kg/day based
on thyroid follicular
hypertrophy/hyperplasia.
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Dermal Short- and No hazard identified.
Intermediate-Term.
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Inhalation, Short-Term (1-30 NOAEL = 7.3 mg/ UFA = 10x Residential LOC 90-day dietary study in rats.
days) and Intermediate-term kg/day. UFH = 10x...... for MOE = 100. MIRD 47923567.
(1-6 months). FQPA SF = 1x... LOAEL = 35.1 mg/kg/day based
on thyroid follicular
hypertrophy/hyperplasia.
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Cancer (oral, dermal, Classification: Not likely to be carcinogenic to humans below a defined dose
inhalation). range.
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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. MOA = mode of action.
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Exposure Assessment
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Dietary exposure from food and feed uses. In evaluating dietary exposure to fluxapyroxad, EPA considered exposure under the petitioned-
for tolerances as well as all existing fluxapyroxad tolerances in 40 CFR 180.666. EPA assessed dietary exposures from fluxapyroxad 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 fluxapyroxad. In estimating acute dietary exposure, EPA used food consumption information from the United States Department of Agriculture (USDA) 2003-2008 Nationwide Continuing Surveys of Food Intake by Individuals (CSFII). As to residue levels in food, EPA used tolerance-level residues adjusted to account for the metabolites of concern (M700F008, and M700F010 (milk only)) and 100 percent crop treated (PCT) assumptions were used. DEEM default and empirical processing factors were used to modify the tolerance values.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 2003-2008 CSFII. As to residue levels in food, a moderately refined chronic dietary exposure analysis was performed for the general U.S. population and various population subgroups. Combined average residue for parent and highest residue for metabolite M700F008 and 100 PCT assumptions were used. For livestock commodities tolerance-level residues adjusted to account for the metabolites of concern (M700F008, M700F010) were used. An assumption of 100 PCT was also used for the chronic dietary analysis. DEEM default and empirical processing factors were used to modify the tolerance values.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that fluxapyroxad 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 percent crop treated (PCT) information. Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide residues that have been measured in food. If EPA relies on such information, EPA must require pursuant to FFDCA section 408(f)(1) that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. For the present action, EPA will issue such data call-ins as are required by FFDCA section 408(b)(2)(E) and authorized under FFDCA section 408(f)(1). Data will be required to be submitted no later than 5 years from the date of issuance of these tolerances.
The Agency did not use PCT information in the dietary assessment for fluxapyroxad; 100 PCT was assumed for all food commodities.
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Dietary exposure from drinking water. The Agency used screening-
level water exposure models in the dietary exposure analysis and risk assessment for fluxapyroxad in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of fluxapyroxad. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www.epa.gov/oppefed1/models/water/index.htm.
Based on the Pesticide Root Zone Model Ground Water (PRZM GW), the estimated drinking water concentrations (EDWCs) of fluxapyroxad for acute exposures are 127 ppb parts per billion (ppb) for surface water and 203 ppb for ground water. The EDWCs for chronic exposures for non-
cancer assessments are 127 ppb for surface water and 188 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For acute dietary risk assessment, the water concentration value of 203 ppb was used to assess the contribution to drinking water. For chronic dietary risk assessment, the water concentration value of 184 ppb was used to assess the contribution to drinking water.
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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).
There are no residential exposure associated with the proposed uses in this action; however, there are existing turf uses that were previously assessed for fluxapyroxad. Although the Agency had conducted a residential exposure assessment for previous fluxapyroxad actions, the Agency completed an updated turf assessment to reflecting an update in the single maximum application rate from 2.47 pounds active ingredient/gallon (lb ai/gallon) to 0.005 lb ai/gallon. The present assessment assumed the following exposure scenarios:
Residential handler: The Agency assessed inhalation exposures to adults from applications only because fluxapyroxad does not pose a dermal risk. Residential handler exposure is expected to be short-term in duration. Intermediate-term exposures are not likely because of the intermittent nature of applications by homeowners.
Post-application exposures: Dermal exposures were not assessed because there is no identified systemic dermal hazard for fluxapyroxad. Post-application inhalation exposure while engaged in activities on or around previously treated turf is generally not quantitatively assessed. The combination of low vapor pressure for chemicals typically used as active ingredients in outdoor residential pesticide products and dilution in outdoor air is likely to result in minimal inhalation exposure. Incidental oral exposure for children is anticipated. The quantitative oral exposure/risk assessment for residential post-application exposures is based on the incidental oral scenario for children 1
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