Source: https://www.federalregister.gov/articles/2012/11/28/2012-28472/dinotefuran-pesticide-tolerances
Timestamp: 2015-11-25 14:21:04
Document Index: 535392598

Matched Legal Cases: ['art 178', 'art 178', 'art 178', 'art 178', 'art 2', '§ 180']

Federal Register | Dinotefuran; Pesticide Tolerances
Dates: This regulation is effective November 28, 2012. Objections and requests for hearings must be received on or before January 28, 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).
77 FR 70908
-70914 (7 pages)
EPA-HQ-OPP-2012-0060
FRL-9365-1
Document Number: 2012-28472
Shorter URL: https://federalregister.gov/a/2012-28472 Related Topics
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Company Notice of Filing for Pesticide Tolerance Mitsui
This regulation establishes tolerances for residues of dinotefuran in or on rice grain, egg, and poultry meat byproducts. Mitsui Chemicals Agro Inc., c/o Landis International, Inc., requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
Table 1—Summary of Toxicological Doses and Endpoints for Dinotefuran for Use in Human Health Risk Assessment
This regulation is effective November 28, 2012. Objections and requests for hearings must be received on or before January 28, 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).
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2012-0060, 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.
Rita Kumar, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone number: (703) 308-8291; email address: kumar.rita@epa.gov.
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-2012-0060 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 January 28, 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-2012-0060, by one of the following methods:
In the Federal Register of May 23, 2012, (77 FR 30481) (FRL-9347-8), 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 1F7953) by Mitsui Chemicals Agro, Inc., c/o Landis International Ltd., P. O. Box 5126, Valdosta, GA 31603. The petition requested that 40 CFR 180.603 be amended by establishing tolerances for residues of the insecticide dinotefuran (RS)-1-methyl-2-nitro-3-((tetrahydro-3-furyl)methyl)guanidine and its major metabolites DN, 1-methyl-3-(tetrahydro-3-furylmethyl)guanidine and UF, 1- methyl-3-(tetrahydro-3-furylmethyl)-urea, in or on rice, grain at 10 parts per million (ppm). That document referenced a summary of the petition prepared by Mitsui Chemicals Agro, Inc., 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 modified the level for which the tolerance is being established for rice, grain. EPA has also established tolerances for residues of dinotefuran in eggs and poultry, meat byproducts. The reason for these changes is explained in Unit IV.C.
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 denotefuran including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with denotefuran follows.
Dinotefuran has low acute toxicity by oral, dermal, and inhalation exposure routes. It is not a dermal sensitizer, but causes a low level of skin irritation. The main target of toxicity is the nervous system but effects on the nervous system were only observed at high doses. Nervous system toxicity was manifested as clinical signs and decreased motor activity seen after acute dosing (in both rats and rabbits) and changes in motor activity which are consistent with effects on the nicotinic cholinergic nervous system seen after repeated dosing. Typically, low to moderate levels of neonicotinoids, such as dinotefuran, activate the nicotinic acetylcholine receptors causing stimulation of the peripheral nervous system (PNS). High levels of neonicotinoids can over stimulate the PNS, maintaining cation channels in the open state which blocks the action potential and leads to paralysis.
Dinotefuran was well tolerated at high doses following dietary administration for 90 days to mice, rats, and dogs. The most sensitive effects were decreases in body weight and/or body weight gain but even these effects occurred at or near the limit dose. Changes in spleen and thymus weights were seen in mice, rats and dogs following subchronic and chronic dietary exposures. However, these weight changes were not corroborated with alterations in hematology parameters, histopathological lesions in these organs, or toxicity to the hematopoietic system. Furthermore, the toxicology data base contains immunotoxicity studies in mice and rats and a developmental immunotoxicity study in rats. In the immunotoxicity studies there were no effect on T-cell dependent antibody response when tested up to the limit dose in male and female mice and in male and female rats. There were no changes in spleen and thymus weight and there were no histopathological lesions in these organs in those studies. In the developmental immunotoxicity study, there was no evidence of an effect on the functionality of the immune system in rats that were exposed to dinotefuran at the limit dose during the prenatal, postnatal, and post-weaning periods. Consequently, the thymus weight changes seen in dogs and the spleen weight changes seen in mice and rats were not considered to be toxicologically relevant.
In the prenatal studies, no maternal or developmental toxicity was seen at the limit dose in rats. In rabbits, maternal toxicity manifested as clinical signs of neurotoxicity but no developmental toxicity was seen. In the reproduction study, parental, offspring, and reproductive toxicity was seen at the limit dose. Parental toxicity included decreased body weight gain, transient decrease in food consumption, and decreased thyroid weights. Offspring toxicity was characterized as decreased forelimb grip strength or hindlimb grip strength in the F 1 pups. There was no adverse effect on reproductive performance at any dose. In the developmental neurotoxicity study, no maternal or offspring toxicity was seen at any dose including the limit dose.
There was no evidence of carcinogenicity in male and female mice and in male and female rats fed diets containing dinotefuran at the limit dose for 78 weeks to mice and 104 weeks to rats. Dinotefuran was non-mutagenic in both in vivo and in vitro assays. Specific information on the studies received and the nature of the adverse effects caused by dinotefuran 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 “Dinotefuran: Human Health Risk Assessment for Proposed Section 3 Uses on Rice and Food/Feed Handling Establishments, and New Horse Spot-On and Total Release Fogger Products,” at pages 40-45 in docket ID number EPA-HQ-OPP-2012-0060.
A summary of the toxicological endpoints for dinotefuran used for human risk assessment is shown in Table 1 of this unit. The dinotefuran hazard profile was updated in the most recent risk assessment completed on July 20, 2012, and nothing has changed since that update. For a more detailed discussion of the endpoint selection, refer to Appendix A.3 on pages 44-47 in the document titled “Dinotefuran: Human Health Risk Assessment for Proposed Section 3 Uses on Tuberous and Corm Vegetables Subgroup 1C, Onion Subgroup 3-07A, Onion Subgroup 3-07B, Small Fruit Subgroup 13-07F, Berry Subgroup 13-07H, Peach, and Watercress, And a Tolerance on Imported Tea” in docket ID number EPA-HQ-OPP-2011-0433.
Table 1—Summary of Toxicological Doses and Endpoints for Dinotefuran for Use in Human Health Risk Assessment Back to Top
FQPA SF = Food Quality Protection Act Safety Factor. 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. UF A= extrapolation from animal to human (interspecies). UF H= potential variation in sensitivity among members of the human population (intraspecies).
NOAEL = 125 mg/kg/day UF A= 10X
UF H= 10X
aRfD = 1.25 mg/kg/day aPAD = 1.25 mg/kg/day
Developmental Toxicity Study in Rabbits LOAEL = 300 mg/kg/day based on clinical signs in does (prone position, panting, tremor and erythema) seen following the first dose on Gestation Day 6.
NOAEL= 99.7 mg/kg/day UF A= 10X
cRfD = 1.0 mg/kg/day cPAD = 1.0 mg/kg/day
Chronic Toxicity/Carcinogenicity Study in Rats LOAEL = 991 mg/kg/day based on decreased body weight gain and nephrotoxicity.
Incidental Oral Short-Term (1-30 days)
Such effects were identified for dinotefuran. In estimating acute dietary exposure, EPA used food consumption information from the U.S. Department of Agriculture (USDA) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to 2008. As to residue levels in food, EPA assumed 100 percent crop treated (PCT) and tolerance-level residues for all current and proposed crops.
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 Intake (CSFII). As to residue levels in food, EPA assumed 100 percent crop treated (PCT) and tolerance-level residues for all current and proposed crops.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residue and/or PCT information in the dietary assessment for dinotefuran. Tolerance level residues and/or 100% CT 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 dinotefuran in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of dinotefuran. 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 Tier 1 Rice Model and Screening Concentration in Ground Water (SCI-GROW) models, the estimated drinking water concentrations (EDWCs) of dinotefuran for acute exposures are estimated to be 269 parts per billion (ppb) for surface water and 4.9 ppb for ground water and for chronic exposures for non-cancer assessments are estimated to be 253-257 ppb, depending upon retention time from 10 to 30 days, for surface water and 4.9 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 269 ppb was used to assess the contribution to drinking water and for chronic dietary risk assessment, the water concentration of value 257 ppb was used to assess the contribution to drinking water.
Dinotefuran is currently registered for the following uses that could result in residential exposures: Turf, ornamentals, vegetable gardens, pet spot-ons, indoor aerosol sprays, crack and crevice sprays. EPA assessed residential exposure using the following assumptions: Each of these existing residential use patterns were reassessed in the latest human health risk assessment using the updated 2012 Residential Standard Operating Procedures and body weights. Refer to the document titled “Dinotefuran: Human Health Risk Assessment for Proposed Section 3 Uses on Tuberous and Corm Vegetables Subgroup 1C, Onion Subgroup 3-07A, Onion Subgroup 3-07B, Small Fruit Subgroup 13-07F, Berry Subgroup 13-07H, Peach, and Watercress, And a Tolerance on Imported Tea” in docket ID number EPA-HQ-OPP-2011-0433.
There are no non-dietary exposure scenarios associated with use on rice. Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
EPA has not found dinotefuran to share a common mechanism of toxicity with any other substances, and dinotefuran does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that dinotefuran does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
2. Prenatal and postnatal sensitivity. In the pre-natal studies, no maternal or developmental toxicity was seen at the limit dose in rats. In rabbits, maternal toxicity manifested as clinical signs of neurotoxicity but no developmental toxicity was seen. In the rat reproduction study, parental, offspring, and reproductive toxicity was seen at the limit dose. Parental toxicity included decreased body weight gain, transient decrease in food consumption, and decreased thyroid weights. Offspring toxicity was characterized as decreased forelimb grip strength or hindlimb grip strength in the F 1 pups. There was no adverse effect on reproductive performance at any dose. In the developmental neurotoxicity study, no maternal or offspring toxicity was seen at any dose including the limit dose.
ii. The neurotoxic potential of dinotefuran has been adequately considered. Dinotefuran is a neonicotinoid and has a neurotoxic mode of pesticidal action. Consistent with the mode of action, changes in motor activity were seen in repeat-dose studies, including the subchronic neurotoxicity study. Additionally, decreased grip strength and brain weight was observed in the offspring of a multi-generation reproduction study albeit at doses close to the limit dose. For these reasons, a developmental neurotoxicity (DNT) study was required. The DNT study did not show evidence of a unique sensitivity of the developing nervous system; no effects on neurobehavioral parameters were seen in the offspring at any dose, including the limit dose.
iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100 percent crop treated (PCT) and tolerance-level residues. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to dinotefuran in drinking water. EPA used similarly conservative assumptions to assess postapplication exposure of children for incidental oral exposures. These assessments will not underestimate the exposure and risks posed by dinotefuran.
1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to dinotefuran will occupy 7.6 percent of the aPAD for all infants < 1 year old, the population group receiving the greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to dinotefuran from food and water will utilize 3.9 percent of the cPAD for children 1 to 2 years old, the population group receiving the greatest exposure. Based on the explanation in Unit III.C.3., regarding residential use patterns, chronic residential exposure to residues of dinotefuran is not expected.
Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 790 for children for co-occurring post-application exposure resulting in the greatest exposure (i.e., from the potentially co-occurring use of the total release fogger product and the existing cat and dog spot-on uses. Because EPA's level of concern for dinotefuran is a MOE of 100 or below, these MOEs are not of concern.
Adequate enforcement methodology a high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS method for the determination of residues of dinotefuran, and the metabolites DN, and UF; an HPLC/ultraviolet (UV) detection method for the determination of residues of dinotefuran; and HPLC/MS and HPLC/MS/MS methods for the determination of DN and UF) is available to enforce the tolerance expression.
The Codex has not established a MRL for dinotefuran for any of the commodities in this rule.
Use of the Organization of Economic Cooperation and Development tolerance calculation procedures indicates that the tolerances for residues in or on rice grain should be established at 9.0 ppm, instead of 10.0 ppm proposed by the registrant. The appropriate residue definition is rice, grain.
EPA has also concluded that poultry tolerances in egg and poultry meat byproducts at 0.01 ppm are now needed as a result of the increased dietary burden resulting from addition of rice grain and bran to the diet.
Therefore, tolerances are established for residues of dinotefuran, (R,S)-1-methyl-2-nitro-3-((tetrahydro-3-furanyl)methyl)guanidine, including its metabolites and degradates, in or on rice, grain at 9.0 ppm, and in or on egg and poultry, meat byproducts at 0.01 ppm.
2.Section 180.603 is amended as follows: i. Add an entry for “rice, grain” in alphabetical order to the table in paragraph (a)(1).
ii. Add entries for “egg” and “poultry, meat byproducts” in alphabetical order to the table in paragraph (a)(2).
iii. Revise paragraph (b) to read as set forth below.
§ 180.603 Dinotefuran, tolerances for residues.
[FR Doc. 2012-28472 Filed 11-27-12; 8:45 am]