Source: https://www.federalregister.gov/documents/2016/04/08/2016-08138/fluazinam-pesticide-tolerances
Timestamp: 2019-06-16 04:42:00
Document Index: 153164723

Matched Legal Cases: ['art 178', 'art 178', 'art 178', 'art 2', 'art 180', '§\u2009180', '§\u2009180']

Federal Register :: Fluazinam; Pesticide Tolerances
This regulation is effective April 8, 2016. Objections and requests for hearings must be received on or before June 7, 2016, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
81 FR 20545
20545-20550 (6 pages)
EPA-HQ-OPP-2015-0197
FRL-9942-99
2016-08138
Fluazinam. Petition for the Establishment of Permanent...
Fluazinam. Human Health Risk Assessment to Support Section 3...
Tier I Estimated Drinking Waters Concentrations of Fluazinam...
Fluazinam Acute and Chronic Aggregate Dietary (Food and...
IR-4 Notice of Filing Pesticide Petition 5E8349 establishing a...
https://www.federalregister.gov/d/2016-08138 https://www.federalregister.gov/d/2016-08138
This regulation establishes tolerances for residues of fluazinam in or on cabbage, mayhaw, the cucurbit vegetable crop group 9, and the tuberous and corm vegetable subgroup 1C and amends the existing tolerance for “vegetable, Brassica leafy, group 5” to read “vegetable, Brassica leafy, group 5, except cabbage.” Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
Start Printed Page 20546
The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2015-0197, 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), West William Jefferson Clinton 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.
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-2015-0197 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 June 7, 2016. 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-2015-0197, by one of the following methods:
In the Federal Register of May 20, 2015 (80 FR 28925) (FRL-9927-39), 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 5E8349) by IR-4, 500 College Road East, Suite 201W, Princeton, NJ 08540. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the fungicide fluazinam (3-chloro-N-[3-chloro-2,6-dinitro-4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2-pyridinamine), including its metabolites and degradates in or on mayhaw at 2.0 parts per million (ppm); cabbage at 3.0 ppm; the squash/cucumber subgroup 9B at 0.05 ppm; and vegetable, tuberous and corm, subgroup 1C at 0.02 ppm. The petition also requested to amend the tolerances in 40 CFR 180.574 in or on the vegetable, Brassica leafy, group 5 at 0.01 by changing it to read “vegetable, Brassica leafy, group 5, except cabbage” at 0.01 ppm and by removing the existing tolerance on potato at 0.02 ppm upon approval of the requested tolerance on the tuberous and corm subgroup 1C. That document referenced a summary of the petition prepared by ISK Biosciences, the registrant, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the notice of filing.
EPA is combining the existing tolerance for the melon subgroup 9A tolerance with the proposed squash/cucumber subgroup 9B tolerance and establishing a tolerance for the entire cucurbit vegetable crop group 9, rather than just subgroup 9B. 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 Start Printed Page 20547sufficient data to assess the hazards of and to make a determination on aggregate exposure for fluazinam including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with fluazinam follows.
The liver is a primary target organ for fluazinam and numerous liver effects were observed in rats, mice, and dogs after oral and dermal exposure. After inhalation exposure, portal of entry effects (increased lung/bronchial weights, alveolar macrophages and peribronchiolar proliferation) were seen.
Clinical signs were observed in an acute oral neurotoxicity study in rats; decreases in motor activity and soft stools were seen on the day of dosing at the limit dose. These effects were attributed to systemic toxicity and were not considered to be evidence of frank neurotoxicity. In two subchronic neurotoxicity studies (evaluated together) in rats, no evidence of neurotoxicity was observed. A neurotoxic lesion was observed initially in long-term studies in mice and dogs; however, the lesion is reversible and was later attributed to the presence of an impurity (Impurity-5) in the technical material. A NOAEL for the impurity was determined (based on the maximum concentration of Impurity-5 in technical grade fluazinam), equivalent to a NOAEL for central nervous system (CNS) effects of 20 mg/kg/day for technical grade fluazinam. The current acute and chronic reference doses selected for risk assessment are lower than the determined NOAEL and thus, protective of any possible neurotoxic effects resulting from exposure to Impurity-5.
In an immunotoxicity study in mice, significant suppressions of anti-SRBC AFC assay response were demonstrated at the highest dose tested indicating potential immunotoxicity. However, clear NOAELs and LOAELs were identified for the effects seen in the study and the points of departure (PODs) and endpoints selected for risk assessment are protective of immunotoxic effects.
There was no evidence of increased quantitative or qualitative susceptibility in the rabbit developmental or rat reproduction studies. However, quantitative susceptibility was seen in rat developmental and developmental neurotoxicity (DNT) studies where fetal/offspring effects were observed in the absence of maternal toxicity. The concern is low for the increased susceptibility noted in the studies since clear NOAELs are established, and the most sensitive endpoints/PODs are used for risk assessment and are protective of the observed susceptibility. Therefore, the Food Quality Protection Act (FQPA) safety factor (SF) has been reduced to 1x.
Fluazinam is classified as having “Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential,” based on increases in thyroid gland follicular cell tumors in male rats and increases in hepatocellular tumors in male mice. Although there is evidence of thyroid tumors in male rats and liver tumors in male mice, the NOAEL used (1.12 mg/kg/day) for establishing the chronic reference dose (cRfD) is approximately 3-fold lower than the lowest dose that induced tumors (3.8 mg/kg/day). The Agency has determined that quantification of cancer risk using a non-linear approach (cRfD) would adequately account for all chronic toxicity, including carcinogenicity, which could result from exposure to fluazinam.
Specific information on the studies received and the nature of the adverse effects caused by fluazinam 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 the document titled “Fluazinam. Human Health Risk Assessment to Support Section 3 Registration for New Uses on Tuberous and Corm, Subgroup 1C, Mayhaw, Squash/Cucumber Subgroup 9B; Amended Uses on Cabbage” on page 44 in docket ID number EPA-HQ-OPP-2015-0197.
A summary of the toxicological endpoints for fluazinam used for human risk assessment is discussed in Unit III.B. of the final rule published in the Federal Register of November 7, 2012 (77 FR 66723) (FRL-9366-6).
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to fluazinam, EPA considered exposure under the petitioned-for tolerances as well as all existing fluazinam tolerances in 40 CFR 180.574. EPA assessed dietary exposures from fluazinam 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 fluazinam. In estimating acute dietary exposure, EPA used food consumption information from the 2003-2008 United States Department of Agriculture's (USDA's) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, the acute analysis is based on tolerance-level residues for all commodities and uses high-end residue estimates for the metabolite AMGT ((3-[[4-amino-3-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]amino]-2-nitro-6-(trifluoromethyl) phenyl]thio]-2-(beta-D-glucopyranosyloxy) propionic acid)). In addition, the acute assessment assumes 100 percent crop treated (PCT).
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA's NHANES/WWEIA. As to residue levels in food, the chronic Start Printed Page 20548analysis is based on tolerance-level residues for all commodities except apples. For apples, the average field trial value was used. As with the acute assessment, it incorporates high-end estimates for AMGT, 100 PCT assumptions, default processing factors for all relevant processed commodities without a separate tolerance.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that a nonlinear RfD approach is appropriate for assessing cancer risk to fluazinam. Cancer risk was assessed using the same exposure estimates as discussed in Unit III.C.1.ii.
2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for fluazinam and its transformation products, including DCPA (6-(4-carboxy-3-chloro-2,6-dinitroanilino)-5-chloronicotinic acid), CAPA (3-chloro-6-(3-chloro-2,6-dinitro-4-trifluoromethyl anilino)nicotinic acid), DAPA (3-chloro-N4-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluorotoluene-3,5,5-triamine; 3-chloro-2(2,6-diamino-3-chloro-α,α,α-trifluoro-p-toluidino)-5-(trifluoromethyl) pyridine), HYPA (5-[[3-chloro-5-(trifluoromethyl-2-pyridyl]amino]-α,α,α-trifluoro-4,6-dinitro-o-cresol), and AMPA (2-(6-amino-3-chloro-α,α,α-trifluoro-2-nitro-p-toluidino)-3-chloro-5-(trifluoromethyl)pyridine).
These simulation models take into account data on the physical, chemical, and fate/transport characteristics of fluazinam and its transformation products. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www2.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​about-water-exposure-models-used-pesticide.
Based on the First Index Reservoir Screening Tool (FIRST) and the Pesticide Root Zone Model Ground Water (PRZM GW) models, the estimated drinking water concentrations (EDWCs) for total residues of fluazinam and its transformation products for acute exposures are estimated to be 226 parts per billion (ppb) for surface water and 137 ppb for ground water and for chronic exposures are estimated to be 37.8 ppb for surface water and 119 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For the acute dietary risk assessment, the water concentration value of 226 ppb was used to assess the contribution to drinking water, and for the chronic dietary risk assessment, the water concentration of value 119 ppb was used to assess the contribution to drinking water.
Fluazinam is currently registered for the following uses that could result in residential exposures: golf course turf. EPA assessed residential exposure using the following assumptions: Only short-term dermal exposure is expected for residential post-application scenarios for children, teens, and adults who could potentially be exposed when they play golf on treated turf. No other residential exposures are expected. Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at http://www2.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​standard-operating-procedures-residential-pesticide.
EPA has not found fluazinam to share a common mechanism of toxicity with any other substances, and fluazinam does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that fluazinam 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://www2.epa.gov/​pesticide-science-and-assessing-pesticide-risks/​cumulative-assessment-risk-pesticides.
2. Prenatal and postnatal sensitivity. There was no evidence of increased quantitative or qualitative susceptibility in the rabbit developmental or rat reproduction studies. However, quantitative susceptibility was seen in rat developmental and DNT studies where fetal/offspring effects were observed in the absence of maternal toxicity. The concern is low for the increased susceptibility noted in the studies since clear NOAELs are established, and the most sensitive endpoints/PODs are used for risk assessment and are protective of the observed susceptibility.
ii. Although indications of neurotoxicity and immunotoxicity were observed in the database for fluazinam, there were clear NOAELs for these effects, and the endpoints and doses for risk assessment are protective of the potential effects.
iii. There is no evidence that fluazinam results in increased susceptibility in the rabbit developmental or rat reproduction studies. However, quantitative susceptibility was seen in rat developmental and DNT studies where fetal/offspring effects were observed in Start Printed Page 20549the absence of maternal toxicity. The concern is low for the increased susceptibility noted in the studies since clear NOAELs are established, and the most sensitive endpoints/PODs are used for risk assessment.
iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100 PCT and tolerance-level residues for all commodities except apples, where anticipated residues were used in the chronic assessment. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to fluazinam and its transformation products in drinking water. EPA used similarly conservative assumptions to assess post-application exposure of children. These assessments will not underestimate the exposure and risks posed by fluazinam.
1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to fluazinam will occupy 32% of the aPAD for females 13-49 years 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 fluazinam from food and water will utilize 92% of the cPAD for all infants, 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 fluazinam is not expected.
3. Short-term risk. Short-term aggregate exposure takes into account short-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Fluazinam is currently registered for uses that could result in short-term residential exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to fluazinam.
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 690 for children 6 to <11 years old, 820 for youth 11 to <16 years old and 890 for adults. Because EPA's level of concern for fluazinam is a MOE of 100 or below, these MOEs are not of concern.
An intermediate-term adverse effect was identified; however, fluazinam is not registered for any use patterns that would result in intermediate-term residential exposure. Intermediate-term risk is assessed based on intermediate-term residential exposure plus chronic dietary exposure. Because there is no intermediate-term residential exposure and chronic dietary exposure has already been assessed under the appropriately protective cPAD (which is at least as protective as the POD used to assess intermediate-term risk), no further assessment of intermediate-term risk is necessary, and EPA relies on the chronic dietary risk assessment for evaluating intermediate-term risk for fluazinam.
5. Aggregate cancer risk for U.S. population. EPA assessed cancer risk using a non-linear approach (i.e., RfD) since it adequately accounts for all chronic toxicity, including carcinogenicity, that could result from exposure to fluazinam. As the chronic dietary endpoint and dose are protective of potential cancer effects, fluazinam is not expected to pose an aggregate cancer risk.
6. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to fluazinam residues.
An adequate Gas Chromatography with Electron Capture Detector (GC/ECD) method is available for enforcing fluazinam tolerances on plant commodities.
The Codex has not established MRLs for fluazinam for any of the commodities covered by this action.
Because the tolerance level for the existing melon subgroup 9A is the same as the squash/cucumber subgroup 9B tolerance the Agency is establishing, the Agency is combining the tolerances for the two subgroups and establishing a tolerance for the entire cucurbit vegetable crop group 9.
Therefore, tolerances are established for residues of fluazinam (3-chloro-N-[3-chloro-2,6-dinitro-4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2-pyridinamine), including its metabolites and degradates in or on mayhaw at 2.0 ppm; cabbage at 3.0 ppm; cucurbit vegetables crop group 9 at 0.07 ppm; and vegetable, tuberous and corm, subgroup 1C at 0.02 ppm. In addition, the existing tolerance on the vegetable, Brassica leafy, group 5 at 0.01 is modified to read “vegetable, Brassica leafy, group 5, except cabbage” at 0.01 ppm and the existing tolerance on potato at 0.02 ppm is removed as unnecessary since it is covered by the tolerance on the tuberous and corm subgroup 1C, and the melon subgroup 9A tolerance is removed since it is now replaced by the cucurbit vegetables crop group 9 tolerance.Start Printed Page 20550
2. In § 180.574, amend the table in paragraph (a)(1) as follows:
a. Alphabetically add the entries “Cabbage” and “Mayhaw”.
b. Remove the entries “Melon subgroup 9A” and “Potato”.
c. Remove the entry for “Vegetable, Brassica leafy, group 5” and alphabetically add entries for “Vegetable, Brassica leafy, group 5, except cabbage” and “Vegetable, tuberous and corm, subgroup 1C“.
§ 180.574
Cabbage 3.0
Mayhaw 2.0
Vegetable, Brassica leafy, group 5, except cabbage 0.01
Vegetable, cucurbit, group 9 0.07
[FR Doc. 2016-08138 Filed 4-7-16; 8:45 am]