Dodine; Pesticide Tolerances
Federal Register, Volume 77 Issue 234 (Wednesday, December 5, 2012)
Federal Register Volume 77, Number 234 (Wednesday, December 5, 2012)
Rules and Regulations
Pages 72232-72237
From the Federal Register Online via the Government Printing Office www.gpo.gov
FR Doc No: 2012-29251
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
EPA-HQ-OPP-2011-0743; FRL-9364-7
Dodine; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of dodine, (N-dodecyl guanidine acetate) in or on multiple commodities and also removes multiple, previously established tolerances which are identified and discussed later in this document. Agriphar S.A., c/o Ceres International LLC requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective December 5, 2012. Objections and requests for hearings must be received on or before February 4, 2013, 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-2011-0743, 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), EPA West 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: Tamue L. Gibson, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone number: (703) 305-9096; email address: gibson.tamue@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://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-2011-0743 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 February 4, 2013. 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-2011-0743, 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 follow the instructions at http://www.epa.gov/dockets/contacts.htm. 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 22, 2012 (77 FR 50661) (FRL-9358-
9), EPA issued a notice pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 1F7872) by Agriphar S.A.,
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c/o Ceres International LLC, 1087 Heartsease Drive, West Chester, PA 19382. The petition requested that 40 CFR 180.172 be amended by establishing tolerances for residues of the fungicide dodine, (N-
dodecyl guanidine acetate), in or on stone fruits (group 12) at 5 parts per million (ppm); tree nuts (group 14) at 0.3 ppm; and almond, hulls at 20 ppm. The petitioner also requested that the tolerances in 40 CFR 180.172 be amended by removing established tolerances for residues of dodine as follows: Cherry, sweet at 3 ppm; cherry, tart at 3 ppm; peach at 5 ppm; pecan at 0.3 ppm; and walnut at 0.3 ppm. These tolerances would be redundant if the crop group tolerances for stone fruits (group 12) and tree nuts (group 14) are established. That notice referenced a summary of the petition prepared by Agriphar S.A., c/o Ceres International LLC, 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 raised the requested tolerance level for almond, hull. The reason for this change is explained in Unit IV.C.
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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 dodine, including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with dodine 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.
Dodine is moderately toxic via the acute oral, dermal and inhalation routes of exposure. It is a severe eye irritant and causes severe dermal irritation; it is not a skin sensitizer. A definitive target organ has not been identified for dodine. The most common effects observed in sub-chronic and chronic studies were decreases in food consumption, body weight and/or body weight gain. Possible neurological clinical signs (excessive salivation and hunched posture/
hypoactivity) were observed in chronic studies in rats and mice but were not dose-related or statistically significant. Excessive salivation in the chronic study in dogs was not consistent with a neurological adverse effect since it was seen prior to dosing and was a persistent finding throughout the study. Therefore, there is no evidence of neurotoxicity and the acute and subchronic neurotoxicity studies are not required (HASPOC, October 25, 2012). The current database does not indicate concerns for immunotoxicity and the registrant has agreed to perform an immunotoxicity study (OCSPP Guideline 870.7800). Therefore, the Food Quality Protection Act (FQPA) safety factor is reduced to 1X.
There is no evidence of increased susceptibility (quantitative or qualitative) in pups versus adults based on rat and rabbit developmental studies and the rat multi-generation reproduction study. In rat and rabbit prenatal developmental studies, there was no toxicity identified in the fetuses up to the highest dose tested (HDT). In the 2-generation reproduction study, decreases in body weight gain and food consumption were seen in pups at the same dose at which maternal toxicity (decreased body weight, body weight gain and food consumption) was observed.
There was equivocal evidence of carcinogenicity in animal carcinogenicity studies; however, a weight-of-evidence evaluation of the carcinogenic potential of dodine was performed, and based on the results it was concluded that dodine should be classified as Not Likely to be Carcinogenic to Humans based on the following:
(1) There was no evidence of tumors in male mice or in rats of either sex;
(2) In female mice, the increase in incidence of combined tumors is marginal (8.3%) compared to historical controls (8%), and there were no pre-neoplastic lesions that can be associated with the tumor response, and therefore no evidence that the high dose was associated with further progression to carcinoma;
(3) There was no evidence of genotoxicity, and therefore no mutagenicity concern; and
(4) The Structure Activity Relationship (SAR) assessment does not indicate probable carcinogenicity. Factors bearing on this weight of the evidence determination are described in ``Dodine: Human Health Risk Assessment for Proposed Use Bananas and Peanuts,'' pages 20-21 in docket ID number EPA-HQ-OPP-2007-0221, at http://www.regulations.gov. In the absence of carcinogenicity concern, risk assessment using the chronic population adjusted dose will be protective for any chronic toxicity.
Specific information on the studies received and the nature of the adverse effects caused by dodine 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 ``Dodine. Amended Human Health Risk Assessment to Support Use on Stone Fruit and Tree Nut Crops,'' pages 14 and 42 in docket ID number EPA-HQ-OPP-2011-0743.
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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
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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 dodine used for human risk assessment is shown in the following Table.
Table--Summary of Toxicological Doses and Endpoints for Dodine for Use in Dietary and Non-Occupational Human
Health Risk Assessments
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Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological
factors assessment effects
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Acute dietary (Females 13-50 years of N/A.................... N/A.................... No appropriate endpoint
age). for females age 13-49.
Acute dietary (General population N/A.................... N/A.................... No appropriate endpoint
including infants and children). identified.
Chronic dietary (All populations).... NOAEL = 2 mg/kg/day.... cRfD=0.02 mg/kg/day.... Chronic toxicity-dog
UFA = 10x.............. LOAEL = 10 mg/kg/day
UFH = 10x.............. based on body weight
loss in females.
FQPA SF = 1x........... cPAD = 0.02 mg/kg/day..
Incidental oral short-term (1 to 30 NOAEL = 26 mg/kg/day... Residential MOE = 100.. 2-Generation
days). UFA = 10x.............. Reproduction-rat
UFH = 10x.............. Offspring LOAEL = 53
mg/kg/day based on
decreased body weight.
Incidental oral intermediate-term (1
to 6 months).
Dermal short-term (1 to 30 days)..... NOAEL = 200 mg/kg/day Residential MOE = 100.. 28-Day Dermal Toxicity-
(HDT). rat LOAEL = not
identified.
Dermal intermediate-term (1 to 6 UFA = 10xUFH = 10x.....
months).
Inhalation short-term(1 to 30 days).. Developmental Study Residential MOE = 100.. Developmental Toxicity
Maternal NOAEL = 10 mg/ Study-rat Maternal
kg/day. LOAEL = 45 mg/kg/day
IAF = 100%............. based on decreased
body weight gain and
food consumption.
Inhalation (1 to 6 months)........... UFA = 10x..............
UFH = 10x..............
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Cancer (oral, dermal, inhalation).... Not likely to be carcinogenic to humans.
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FQPA SF = Food Quality Protection Act Safety Factor. HDT= Highest Dose Tested. IAF = inhalation absorption rate.
LOAEL = lowest-observed-adverse-effect-level. LOC = level of concern. mg/kg/day = milligram/kilogram/day. MOE
= margin of exposure. NOAEL = no-observed-adverse-effect-level. PAD = population adjusted dose (a = acute, c =
chronic). RfD = reference dose. UFA = extrapolation from animal to human (interspecies). UFH = potential
variation in sensitivity among members of the human population (intraspecies).
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Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to dodine, EPA considered exposure under the petitioned-for tolerances as well as all existing dodine tolerances in 40 CFR 180.172. EPA assessed dietary exposures from dodine 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.
No such effects were identified in the toxicological studies for dodine; therefore, a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 1994-1996 and 1998 Continuing Survey of Food Intakes by Individuals (CSFII). As to residue levels in food, EPA assumed tolerance level residues for all treated crops. In terms of extent of usage, percent crop treated (PCT) information was used for apples, cherries, peaches, pears, peanuts, pecans, and strawberries. One hundred PCT was assumed for the remainder of crops.
iii. Cancer. Based on the data discussed in Unit III.A., EPA determined that dodine did not pose a carcinogenicity concern and that risk assessment using the chronic population adjusted dose will be protective for any chronic toxicity. Accordingly, no exposure assessment, separate from the chronic assessment, was conducted with regard to cancer risk.
iv. PCT information. Section 408(b)(2)(F) of FFDCA states that the Agency may use data on the actual percent of food treated for assessing chronic dietary risk only if:
Condition a: The data used are reliable and provide a valid basis to show what percentage of the food derived from such crop is likely to contain the pesticide residue.
Condition b: The exposure estimate does not underestimate exposure for any significant subpopulation group.
Condition c: Data are available on pesticide use and food consumption in a particular area, the exposure estimate does not understate exposure for the population in such area.
In addition, the Agency must provide for periodic evaluation of any estimates used. To provide for the periodic evaluation of the estimate of PCT as required by FFDCA section 408(b)(2)(F), EPA may require registrants to submit data on PCT.
The Agency estimated the PCT for existing uses as follows:
The Agency used the following PCT information for the currently registered uses of dodine: 10% PCT for pecans, 5% PCT for cherries and pears, 2.5% PCT
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for apples and peanuts along with 1% PCT for peaches and strawberries.
In most cases, EPA uses available data from U.S. Department of Agriculture/National Agricultural Statistics Service (USDA/NASS), proprietary market surveys, and the National Pesticide Use Database for the chemical/crop combination for the most recent 6-7 years. EPA uses an average PCT for chronic dietary risk analysis. The average PCT figure for each existing use is derived by combining available public and private market survey data for that use, averaging across all observations, and rounding to the nearest 5%, except for those situations in which the average PCT is less than 1. In those cases, 1% is used as the average PCT and 2.5% is used as the maximum PCT. EPA uses a maximum PCT for acute dietary risk analysis. The maximum PCT figure is the highest observed maximum value reported within the recent 6 years of available public and private market survey data for the existing use and rounded up to the nearest multiple of 5%.
The Agency believes that the three conditions discussed in Unit III.C.1.iv. have been met. With respect to Condition a, PCT estimates are derived from Federal and private market survey data, which are reliable and have a valid basis. The Agency is reasonably certain that the percentage of the food treated is not likely to be an underestimation. As to Conditions b and c, regional consumption information and consumption information for significant sub-populations is taken into account through EPA's computer-based model for evaluating the exposure of significant subpopulations including several regional groups. Use of this consumption information in EPA's risk assessment process ensures that EPA's exposure estimate does not understate exposure for any significant subpopulation group and allows the Agency to be reasonably certain that no regional population is exposed to residue levels higher than those estimated by the Agency. Other than the data available through national food consumption surveys, EPA does not have available reliable information on the regional consumption of food to which dodine may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for dodine in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of dodine. 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 FQPA Index Reservoir Screening Tool (FIRST) and Screening Concentration in Ground Water (SCI-GROW) models, the estimated drinking water concentrations (EDWCs) of dodine for chronic exposures for non-cancer assessments are estimated to be 1.79 parts per billion (ppb) for surface water and 50 studies via the oral, dermal and inhalation routes, a metabolism study, and a complete mutagenicity battery. The current database does not indicate neurotoxicity or immunotoxicity concerns. Thus, EPA has waived the acute and subchronic neurotoxicity studies. An immunotoxicity study is required pursuant to the recent amendment of EPA's data regulations to evaluate the potential of a repeated chemical exposure to produce adverse effects (i.e., suppression) on the immune system. However, because no immunotoxicity was observed in available toxicity studies, EPA has confidence that this study is unlikely to change the POD in assessing risk to infants and children.
a. There is no evidence that dodine results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study.
b. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on Agency recommended tolerance-level residues and health protective modeling assumptions. Although PCT estimates were used for crops with existing tolerances, the use of tolerance values for residue levels will likely overestimate actual exposures. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to dodine in drinking water. EPA used similarly conservative assumptions to assess postapplication exposure of children, as well as incidental oral exposure of children and incidental oral exposure of toddlers. These assessments will not underestimate the exposure and risks posed by dodine.
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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.
1. Acute risk. An acute aggregate risk assessment takes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse effect resulting from a single oral exposure was identified and no acute dietary endpoint was selected. Therefore, dodine is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to dodine from food and water will utilize 21% of the cPAD for all infants
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