Pesticide Tolerances:
Federal Register Volume 76, Number 193 (Wednesday, October 5, 2011)
Rules and Regulations
Pages 61587-61592
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
FR Doc No: 2011-25704
ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180
EPA-HQ-OPP-2011-0053; FRL-8884-2
Prothioconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of prothioconazole in or on multiple commodities which are identified and discussed later in this document. Bayer CropScience requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective October 5, 2011. Objections and requests for hearings must be received on or before December 5, 2011, 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: EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2011-0053. All documents in the docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is not publicly available, e.g., Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The Docket Facility telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Tawanda Maignan, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 308-8050; e-mail address: maignan.tawanda@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.
Potentially affected entities may include, but are not limited to those engaged in the following activities:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather to provide a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
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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://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
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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-2011-0053 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 5, 2011. 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 that does not contain any 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 a copy of your non-CBI objection or hearing request, identified by docket ID number EPA-HQ-OPP-2011-0053, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only accepted during the Docket Facility's normal hours of operation (8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed information. The Docket Facility telephone number is (703) 305-5805.
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Summary of Petitioned-For Tolerance
In the Federal Register of March 29, 2011 (76 FR 17375) (FRL-8867- 4), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of pesticide petitions (PPs 0F7714 and 0F7715) by Bayer CropScience, P.O. Box 12014, 2 T.W.
Alexander Drive, Research Triangle Park, NC 27709. The petition requested that 40 CFR 180.626 be amended by establishing tolerances for residues of the fungicide prothioconazole, 2-[2-(1-chlorocyclopropyl)- 3-(2-chlorophenyl-2-hydroxypropyl]-1,2-dihydro-3H-1,2,4-triazole-3- thione and its desthio metabolite, in or on the raw or processed agricultural commodity rice,
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grain at 0.25 parts per million (ppm); rice, hulls at 1.0 ppm; alfalfa, forage and alfalfa, hay at 0.02 ppm and potato, tuber at 0.02 ppm (PP 0F7714). In a separate petition (PP 0F7715) Bayer CropScience also proposed use of the currently established tolerances for residues of prothioconazole, 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl-2- hydroxypropyl]-1,2-dihydro-3H-1,2,4-triazole-3-thione and its desthio metabolite, in or on the raw agricultural commodities pea and bean, dried shelled, except soybean, subgroup 6C; soybean, forage; soybean, hay; soybean, seed; rice, seed to support the use of prothioconazole as a seed treatment on these crops. That notice referenced a summary of the petitions prepared by Bayer CropScience, 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 determined that it is appropriate to modify the existing grain crop groups rather than establish separate rice grain and rice straw tolerances. The rice grain tolerance will now be covered by the modified tolerance of 0.35 ppm for grain, cereal group 15, except sweet corn and sorghum. Likewise, the rice straw tolerance will now be covered by the modified tolerance of 5.0 ppm for grain, cereal, forage, fodder, and straw, group 16, except sorghum; straw. Also, the EPA is establishing a tolerance for rice hulls at 0.90 ppm, instead of the proposed tolerance of 1.0 ppm. The reasons 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. * *
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Consistent with section 408(b)(2)(D) of FFDCA, and the factors specified in section 408(b)(2)(D) of FFDCA, 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 prothioconazole including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with prothioconazole 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.
Prothioconazole has low acute toxicity by oral, dermal, and inhalation routes. It is not a dermal sensitizer, or a skin or eye irritant. Prothioconazole's metabolite, prothioconazole-desthio, also has low acute toxicity by oral, dermal, and inhalation routes. It is not a dermal sensitizer, or a skin irritant, but it is a slight eye irritant. The subchronic and chronic studies show that the target organs at the lowest observable adverse effects level (LOAEL) include the liver, kidney, urinary bladder, thyroid and blood. In addition, the chronic studies showed body weight and food consumption changes, and toxicity to the lymphatic and GI systems.
Prothioconazole and its metabolites may be developmental toxicants, producing effects including malformations in the conceptus at levels equal to or below maternally toxic levels in some studies; particularly those studies conducted using prothioconazole-desthio. Reproduction studies in the rat with prothioconazole and prothioconazole-desthio suggest that these chemicals may not be reproductive toxicants. Acute and subchronic neurotoxicity studies were conducted in the rat using prothioconazole. A developmental neurotoxicity study was conducted in the rat using prothioconazole-desthio.
The available data show that the prothioconazole-desthio metabolite produces toxicity at lower dose levels in subchronic, developmental, reproductive, and neurotoxicity studies as compared with prothioconazole and the two additional metabolites that were tested.
The available carcinogenicity and/or chronic studies in the mouse and rat, using both prothioconazole and prothioconazole-desthio, show no increase in tumor incidence. Therefore, EPA has concluded that prothioconazole and its metabolites are not carcinogenic, and are classified as ``Not likely to be Carcinogenic to Humans'' according to the 2005 Cancer Guidelines.
Specific information on the studies received and the nature of the adverse effects caused by prothioconazole as well as the no-observed- adverse-effect-level (NOAEL) and the LOAEL from the toxicity studies are discussed in the final rule published in the Federal Register of
May 28, 2010 (75 FR 29910) (FRL-8828-6).
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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.
A summary of the toxicological endpoints for prothioconazole used for human risk assessment is discussed in Unit III.B. of the final rule published in the Federal Register of May 28, 2010 (75 FR 29910) (FRL- 8828-6).
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Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to prothioconazole and its metabolites and/or degradates, EPA considered exposure under the petitioned-for tolerances as well as all existing prothioconazole tolerances in 40 CFR 180.626. EPA assessed dietary exposures from prothioconazole 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.
In estimating acute dietary exposure, EPA used food consumption information from the United States Department of Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of Food Intake by
Individuals (CSFII). As to residue levels in food, EPA conducted a moderately refined acute dietary exposure assessment. Empirical processing factors, average field trial residues (since all of the plant commodities included in this assessment are blended food forms, except sweet corn), and livestock commodity residues derived from feeding studies and a reasonably balanced dietary burden (RBDB) were incorporated into the moderately refined acute assessment. The assessment also assumed 100 percent crop treated (PCT). Since no observed effects would be attributable to a single dose exposure for the general U.S. population (including infants and children), females 13-49 years of age was the only population subgroup included in the acute assessment. ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 1994-1996 and 1998 CSFII. As to residue levels in food, EPA conducted a moderately refined chronic dietary exposure assessment. Empirical processing factors, average field trial residues, and livestock commodity residues derived from feeding studies and a reasonably balanced dietary burden (RBDB) were incorporated into the chronic assessment; 100 PCT was assumed. iii. Cancer. EPA determines whether quantitative cancer exposure and risk assessments are appropriate for a food-use pesticide based on the weight of the evidence from cancer studies and other relevant data.
Cancer risk is quantified using a linear or non-linear approach. If sufficient information on the carcinogenic mode of action is available, a threshold or non-linear approach is used and a cancer RfD is calculated based on an earlier non-cancer key event. If carcinogenic mode of action data are not available, or if the mode of action data determines a mutagenic mode of action, a default linear cancer slope factor approach is utilized.
Based on the data summarized in Unit III.A., EPA has concluded that prothioconazole is ``Not Likely to be Carcinogenic 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. Average 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 prothioconazole in drinking water. These simulation models take into account data on the physical, chemical, and fate/ transport characteristics of prothioconazole. 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/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of prothioconazole for the acute dietary risk assessment, the estimated surface water concentration value of 94.7 parts per million (ppb) was used to assess the contribution to drinking water. For the chronic dietary risk assessment, the estimated surface water concentration value of 84.3 ppb was used to assess the contribution to drinking water. Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. 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).
Prothioconazole 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.''
Prothioconazole is a member of the triazole-containing class of pesticides. Although conazoles act similarly in plants (fungi) by inhibiting ergosterol biosynthesis, there is not necessarily a relationship between their pesticidal activity and their mechanism of toxicity in mammals. Structural similarities do not constitute a common mechanism of toxicity. Evidence is needed to establish that the chemicals operate by the same, or essentially the same, sequence of major biochemical events. In conazoles, however, a variable pattern of toxicological responses is found. Some are hepatotoxic and hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some induce developmental, reproductive, and neurological effects in rodents. Furthermore, the conazoles produce a diverse range of biochemical events including altered cholesterol levels, stress responses, and altered DNA methylation. It is not clearly understood whether these biochemical events are directly connected to their toxicological outcomes. Thus, there is currently no evidence to indicate that conazoles share common mechanisms of toxicity and EPA is not following a cumulative risk approach based on a common mechanism of toxicity for the conazoles. 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://www.epa.gov/pesticides/cumulative.
Prothioconazole is a triazole-derived pesticide. Triazole-derived pesticides can form the common metabolite, 1,2,4-triazole and three triazole conjugates (triazole alanine, triazole acetic acid, and triazolylpyruvic acid). To support existing tolerances and to establish new tolerances for triazole-derivative pesticides, including prothioconazole, EPA conducted a human health risk
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assessment for exposure to 1,2,4-triazole, triazole alanine, and triazole acetic acid resulting from the use of all current and pending uses of any triazole-derived fungicide. The risk assessment is a highly conservative, screening-level evaluation in terms of hazards associated with common metabolites (e.g., use of a maximum combination of uncertainty factors) and potential dietary and non-dietary exposures
(i.e., high end estimates of both dietary and non-dietary exposures).
In addition, the Agency retained the additional 10X FQPA safety factor
(SF) for the protection of infants and children. The assessment included evaluations of risks for various subgroups, including those comprised of infants and children. The Agency's risk assessment can be found in the propiconazole reregistration docket at http://www.regulations.gov, docket ID number EPA-HQ-OPP- 2005-0497 and an update to assess the addition of the commodities included in this action may be found in docket ID number EPA-HQ-OPP-2010-0621 in the document titled ``Common Triazole Metabolites: Updated Aggregate Human
Health Risk Assessment to Address Tolerance Petitions for
Metconazole.''
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Safety Factor for Infants and Children 1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the Food Quality
Protection Act Safety Factor (FQPA SF). In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor. 2. Prenatal and postnatal sensitivity. There is evidence of increased susceptibility following prenatal/or postnatal exposure in: i. Rat developmental toxicity studies with prothioconazole as well as its prothioconazole-desthio and sulfonic acid K salt metabolites. ii. Rabbit developmental toxicity studies with prothioconazole- desthio. iii. A rat developmental neurotoxicity study with prothioconazole- desthio; and iv. Multi-generation reproduction studies in the rat with prothioconazole-desthio. Effects include skeletal structural abnormalities, such as cleft palate, deviated snout, malocclusion, extra ribs, and developmental delays. Available data also show that the skeletal effects such as extra ribs are not completely reversible after birth in the rat, but persist as development continues.
Although increased susceptibility was seen in these studies, the
Agency concluded that there is a low concern and no residual uncertainties for prenatal and/or postnatal toxicity effects of prothioconazole because:
Developmental toxicity NOAELs and LOAELs from prenatal exposure are well characterized after oral and dermal exposure;
The off-spring toxicity NOAELs and LOAELs from postnatal exposures are well characterized; and
The NOAEL for the fetal effect malformed vertebral body and ribs is used for assessing acute risk of females 13 years and older and, because it is lower than the NOAELs in other developmental studies, is protective of all potential developmental effects. 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: i. The toxicity database for prothioconazole is complete, including required functional immunotoxicity testing. The EPA began requiring functional immunotoxicity testing of all food and non-food use pesticides on December 26, 2007. ii. There is an acceptable battery of neurotoxicity studies including a developmental neurotoxicity study. Although offspring neurotoxicity was found, characterized by peripheral nerve lesions in the developmental neurotoxicity studies on prothioconazole-desthio, the increase was seen only in the highest dose group at 105 mg/kg/day, was not considered treatment related, and a clear NOAEL was established for this study. iii. Although increased susceptibility was seen in the developmental and reproduction studies, the Agency concluded that there is a low concern and no residual uncertainties for prenatal and/or postnatal toxicity effects of prothioconazole for the reasons explained in Unit III.D.2. iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessment is moderately refined utilizing empirical processing factors, 100 PCT, average crop field trial residue levels, and livestock maximum residues. Results from ruminant feeding studies and poultry metabolism studies were used to determine the maximum residue levels for livestock commodities. The crop field trials were performed using maximum application rates and minimum pre-harvest intervals. Although the Agency is requiring extended confirmatory storage stability data; interim storage stability data do not indicate that residue concentrations decline and therefore the assessment should not underestimate risk from dietary exposure. EPA made conservative (protective) assumptions in the ground water and surface water modeling used to assess exposure to prothioconazole in drinking water. These assessments will not underestimate the exposure and risks posed by prothioconazole.
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Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.
Based on the proposed and existing crop uses for prothioconazole, dietary aggregate exposures (i.e., food plus drinking water) are anticipated. There are no residential uses for prothioconazole and, therefore, no residential exposures are anticipated. Consequently, only dietary (food plus drinking water) exposures were aggregated for this assessment. 1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and drinking water to prothioconazole will occupy 24% of the aPAD for females 13-49 years of age, the only population group at risk for acute effects. 2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to prothioconazole from food and drinking water will utilize 21% of the cPAD for the general U.S. population and 62% of the cPAD for all infants
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