Environmental Protection Agency (EPA).
Final rule.
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).
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
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
Tawanda Maignan, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001;
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
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
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:
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In the
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.
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 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.
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
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
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
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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.
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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.
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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.
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Prothioconazole is not registered for any specific use patterns that would result in residential exposure.
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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
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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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.
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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.
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 (
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Adequate liquid chromatography methods with tandem mass spectrometry detection (LC/MS/MS) are available to enforce the tolerance expression.
The method may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755–5350; telephone number: (410) 305–2905; e-mail address:
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 U.N. 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 established MRLs for residues of desthio-prothioconazole in barley at 0.2 ppm; oats, rye, and wheat at 0.05 ppm each; in the fodder (dry) of cereal grains at 5 ppm; and in the straw (dry) of cereal grains at 4 ppm. There are currently no established Mexican MRLs for prothioconazole. Canadian MRLs have been established for prothioconazole
The tolerance definition for plant commodities in Canada was recently changed and is now harmonized with the U.S. residue definition. The barley tolerance of Canada agrees with the U.S. tolerance for cereal grains (except sweet corn, sorghum, and rice) of 0.35 ppm. However, the Canada tolerance for wheat is lower (0.07 ppm) than the existing U.S. group tolerance. EPA establishes crop group tolerances, as opposed to individual commodity tolerances, whenever there are adequate data for the representative commodities of that group and proposed use. There must be an acceptable range of residues over all the representative commodities. Wheat falls under this crop group practice in this case. Canada does not routinely establish animal feed commodity tolerances, and therefore there are no harmonization issues with forage, stover, hay, and straw.
The proposed rice grain tolerance level of 0.25 ppm is lower than the existing tolerance level (0.35 ppm) for grain, cereal group 15, except rice and sweet corn and sorghum. The existing cereal grain group 15 tolerance excludes rice, but the present evaluation of rice field trial data allows expansion of that group to include rice. Therefore, in this action, EPA is revising the existing cereal group to read grain, cereal group 15 (except sweet corn and sorghum). Likewise, the rice straw tolerance level is lower than the existing tolerance level (5.0 ppm) for grain, cereal, forage, fodder, and straw, group 16, except sorghum and rice straw, and therefore this crop group is being revised to include rice straw. Also, the submitted data support a tolerance of 0.90 ppm for rice hulls as determined from the rice to hull processing factor (from the rice processing study) applied to the highest average field trial residue, or 4.4 × 0.19 ppm, or 0.9 ppm instead of the proposed tolerance of 1.0 ppm.
Therefore, tolerances are established for residues of prothioconazole (2-[2-(1-chlorocylcopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1,2-dihydro-3
Further, seed treatment uses on soybean, dried shelled pea and bean (except soybean) subgroup 6C and rice are covered by existing and currently established tolerances for these commodities.
This final rule establishes tolerances under section 408(d) of FFDCA in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled
Since tolerances and exemptions that are established on the basis of a petition under section 408(d) of FFDCA, such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601
This final rule directly regulates growers, food processors, food handlers, and food retailers, not States or Tribes, nor does this action alter the
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 of 1995 (NTTAA), Public Law 104–113, section 12(d) (15 U.S.C. 272 note).
The Congressional Review Act, 5 U.S.C. 801
Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping requirements.
Therefore, 40 CFR chapter I is amended as follows:
21 U.S.C. 321(q), 346a and 371.
(a) * * * (1) * * *