Indaziflam; Pesticide Tolerances
Federal Register, Volume 79 Issue 19 (Wednesday, January 29, 2014)
Federal Register Volume 79, Number 19 (Wednesday, January 29, 2014)
Rules and Regulations
Pages 4624-4630
From the Federal Register Online via the Government Printing Office www.gpo.gov
FR Doc No: 2014-01363
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
EPA-HQ-OPP-2013-0014; FRL-9903-88
Indaziflam; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of indaziflam in or on coffee, banana, and palm oil. Bayer Crop Science requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective January 29, 2014. Objections and requests for hearings must be received on or before March 31, 2014, 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-2013-0014, 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: Lois Rossi, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; 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.
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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-2013-0014 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 March 31, 2014. 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-2013-0014, 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 February 15, 2013 (78 FR 32) (FRL-9378-
4), 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 2E8125) by Bayer Crop Science, 2 T.W. Alexander Drive; P.O. Box 12014; Research Triangle Park, NC 27709. The petition requested that 40 CFR 180.653 be amended by establishing tolerances for residues of the herbicide indaziflam, N-(1R, 2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-
yl-1,3,5-triazine-2,4-diamine-6-(1-fluoroethyl) and its fluoroethyl-
indaziflam metabolite, each expressed as the parent compound, in or on coffee at 0.01 part per million (ppm), banana at 0.01 ppm, and palm oil at 0.03 ppm. That document referenced a summary of the petition prepared by Bayer CropScience, the registrant, which is available in the docket, http://www.regulations.gov. A comment was received on the notice of filing. EPA's response to this comment is discussed 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 indaziflam including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with indaziflam 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.
The nervous system is the major target for indaziflam toxicity in rats and dogs, with the dog being the more sensitive species based on neuropathology (degenerative nerve fibers in the brain, spinal cord and sciatic nerve). Clinical signs of neurotoxicity were observed in the acute, subchronic, and developmental neurotoxicity studies and consisted primarily of tremors, changes in activity and reactivity, repetitive chewing, dilated pupils, and oral, perianal, and nasal staining. Similar clinical signs of neurotoxicity were observed in the 2-generation reproduction study, the rat chronic toxicity study, and the combined rat carcinogenicity/chronic toxicity study. Neuropathology findings were also observed in the rat manifested as focal/multifocal vacuolation of the median eminence of the brain and the pituitary pars nervosa and degenerative nerve fibers in the gasserian ganglion, sciatic nerve, and tibial nerve. Evidence of neurotoxicity was not seen in the mouse.
Other organs affected by indaziflam in mice and rats include the kidney, liver, thyroid, stomach, seminal vesicles, and ovaries. Effects on the kidney were observed following chronic exposure in rats and mice while effects on the liver were observed following chronic exposure in the rat. Effects on the thyroid were only observed in multiple
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dose rat studies. Chronic exposures also lead to atrophied or small seminal vesicles in male and female mice. However, these effects occurred at higher doses than those at which neurotoxicity was observed in the dog.
Decreased body weight gain was observed in most studies following exposure to indaziflam. There was no evidence of immunotoxicity in the available studies, which included a guideline immunotoxocity study in the rat. No systemic effects were observed in the rat following a 28-
day dermal exposure period.
No evidence of increased quantitative or qualitative susceptibility was seen in developmental toxicity studies in rats and rabbits or in a reproduction study in rats. In the rat developmental toxicity study, decreased fetal weight was observed in the presence of maternal effects that included decreased body weight gain and food consumption. No developmental effects were observed in rabbits up to maternally toxic dose levels. Decreased pup weight and delays in sexual maturation (preputial separation in males and vaginal patency in females) were observed in the rat 2-generation reproductive toxicity study, along with clinical signs of toxicity, at a dose causing parental toxicity that included coarse tremors, renal toxicity and decreased weight gain. In the developmental neurotoxicity study, transiently decreased motor activity (PND 21 only) in male offspring was observed and was considered a potential neurotoxic effect. It was observed at a dose that also caused clinical signs of neurotoxicity along with decreased body weight in maternal animals.
Indaziflam showed no evidence of carcinogenicity in the 2-year dietary rat and mouse bioassays. All genotoxicity studies that were conducted on indaziflam were negative.
Testing in acute lethality studies with indaziflam resulted in low toxicity via the oral, dermal, and inhalation routes of exposure. Indaziflam was not an irritant to eyes Category IV) or skin and was not a skin sensitizer.
Specific information on the studies received and the nature of the adverse effects caused by indaziflam 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 Indaziflam. Human Health Risk Assessment to Support Proposed New Import Tolerances (Without a U.S. Registration) on Banana, Coffee, and Palm Oil at page 33 in docket ID number EPA-HQ-OPP-2013-0014.
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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 indaziflam used for human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Indaziflam for Use in Human Health Risk Assessment
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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 (General population NOAEL = 7.5 mg/kg/day.. Acute RfD = 0.075 mg/kg/ Subchronic Gavage
including infants and children). UFA = 10x.............. day. Toxicity Study in
UFH =10x............... aPAD = 0.075 mg/kg/day. Dogs.
FQPA SF = 1x........... LOAEL = 15 mg/kg/day
based on axonal
degenerative
microscopic findings
in the brain, spinal
cord and sciatic
nerve.
Chronic dietary (All populations).... NOAEL= 2 mg/kg/day..... Chronic RfD = 0.02 mg/ Chronic Dietary
UFA = 10x.............. kg/day. Toxicity Study in
UFH = 10x.............. cPAD = 0.02 mg/kg/day.. Dogs.
FQPA SF = 1x........... LOAEL = 6/7 mg/kg/day M/
F based on nerve fiber
degenerative lesions
in the brain, spinal
cord and sciatic
nerve.
Incidental oral short-term (1 to 30 NOAEL= 7.5 mg/kg/day... LOC for MOE = 100...... Subchronic Gavage
days). UFA = 10x.............. Toxicity Study in
UFH = 10x.............. Dogs.
FQPA SF = 1x........... LOAEL = 15 mg/kg/day
based on axonal
degenerative
microscopic findings
in the brain, spinal
cord and sciatic
nerve.
Incidental oral intermediate-term (1 NOAEL= 7.5 mg/kg/day... LOC for MOE = 100...... Subchronic Gavage
to 6 months). UFA = 10x.............. Toxicity Study in
UFH = 10x.............. Dogs.
FQPA SF = 1x........... LOAEL = 15 mg/kg/day
based on axonal
degenerative
microscopic findings
in the brain, spinal
cord and sciatic
nerve.
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Dermal short-term (1 to 30 days)..... Dermal (or oral) study LOC for MOE = 100...... Subchronic Gavage
NOAEL = 7.5 mg/kg/day Toxicity Study in
(dermal absorption Dogs.
factor) = 7.3%. LOAEL = 15 mg/kg/day
UFA = 10x.............. based on axonal
UFH = 10x.............. degenerative
FQPA SF = 1x........... microscopic findings
in the brain, spinal
cord and sciatic
nerve.
Dermal intermediate-term (1 to 6 Dermal (or oral) study LOC for MOE = 100...... Subchronic Gavage
months). NOAEL = 7.5 mg/kg/day Toxicity Study in
(dermal absorption Dogs.
factor) = 7.3%. LOAEL = 15 mg/kg/day
UFA = 10x.............. based on axonal
UFH = 10x.............. degenerative
FQPA SF = 1x........... microscopic findings
in the brain, spinal
cord and sciatic
nerve.
Inhalation short-term (1 to 30 days). Inhalation (or oral) LOC for MOE = 100...... Subchronic Gavage
study NOAEL = 7.5 mg/ Toxicity Study in
kg/day (Inhalation Dogs.
toxicity considered LOAEL = 15 mg/kg/day
equivalent to oral based on axonal
toxicity). degenerative
UFA = 10x.............. microscopic findings
UFH = 10x.............. in the brain, spinal
FQPA SF = 1x........... cord and sciatic
nerve.
Inhalation (1 to 6 months)........... Inhalation (or oral) LOC for MOE = 100...... Subchronic Gavage
study NOAEL = 7.5 mg/ Toxicity Study in
kg/day (Inhalation Dogs.
toxicity considered LOAEL = 15 mg/kg/day
equivalent to oral based on axonal
toxicity). degenerative
UFA = 10x.............. microscopic findings
UFH = 10x.............. in the brain, spinal
FQPA SF = 1x........... cord and sciatic
nerve.
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Cancer (Oral, dermal, inhalation).... No evidence of carcinogenicity. Classified as ``Not Likely to be
Carcinogenic to Humans.''
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FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
of concern. mg/kg/day = milligrams/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor.
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among
members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL.
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Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to indaziflam, EPA considered exposure under the petitioned-
for tolerances as well as all existing indaziflam tolerances in 40 CFR 180.653. EPA assessed dietary exposures from indaziflam 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 indaziflam. In estimating acute dietary exposure, EPA used food consumption information from the United States Department of Agriculture (USDA)'s 2003-2008 National Health and Nutrition Examination Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in food, the acute dietary assessment assumes 100% crop treated (PCT) along with tolerance or maximum residue level estimates for indaziflam. It used DEEM-WWEIA analyses to estimate the dietary exposure of the U.S. population and various population subgroups.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA's 2003-2008 NHANES/WWEIA. As to residue levels in food, the chronic dietary assessment used the same residue levels, analysis and PCT assumptions used in the acute dietary assessment.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that indaziflam 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 PCT information. EPA did not use anticipated residue and/or PCT information in the dietary assessment for indaziflam. Tolerance level residues and/or 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 indaziflam in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of indaziflam. 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 indaziflam equivalents for acute exposures are estimated to be 84 parts per billion (ppb) for surface water and 3.7 ppb for ground water. For chronic exposures for non-cancer assessments
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the estimates are 26 ppb for surface water and 3.7 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 84 ppb was used to assess the contribution to drinking water. For chronic dietary risk assessment, the water concentration of value 26 ppb was used to assess the contribution to drinking water.
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). Indaziflam is currently registered for the following uses that could result in residential exposures: Home lawn/turf and gardens/tree uses. There are no new indaziflam residential uses associated with this regulatory action. A re-evaluation of existing indaziflam residential uses was conducted to incorporate updated policies and guidance in place since previous risk assessments. Short-term dermal and inhalation handler exposures for residential are expected for those making applications at their homes and short-term dermal and incidental oral exposures are expected via contact with residues following applications in outdoor home environments. For adults, the highest exposure was from dermal post-application high-contact (playing) activities on treated turf during spray applications. The highest exposure scenarios for children 1
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