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Federal Register / Vol. 86, No. 30 / Wednesday, February 17, 2021 / Rules and Regulations Mail: OPP Docket, Environmental Protection Agency Docket Center EPA/
DC, 28221T, 1200 Pennsylvania Ave.
NW, Washington, DC 204600001.
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.html.
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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II. Summary of Petitioned-For Tolerance In the Federal Register of February 11, 2020 85 FR 7708 FRL1000502, EPA issued a document pursuant to FFDCA section 408d3, 21 U.S.C.
346ad3, announcing the filing of a pesticide petition PP 9E8757 by Nissan Chemical Corporation, 51, Nihonbashi 2-Chome Chuo-Ku, Tokyo 1016119
Japan, c/o Lewis and Harrison, 2461
South Clark Street, Suite 710, Arlington, VA 22202. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the insecticide fluxametamide, including its metabolites and degradates, in or on tea at 5 parts per million ppm. That document referenced a summary of the petition prepared by Nissan Chemical Corporation c/o Lewis and Harrison, 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 revised the commodity definition and is establishing a tolerance for tea, dried and tea, instant. The reasons for these changes are explained in Unit IV.C.
III. Aggregate Risk Assessment and Determination of Safety Section 408b2Ai 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 408b2Aii 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 408b2C of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide
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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 408b2D, and the factors specified in FFDCA section 408b2D, 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 fluxametamide including exposure resulting from the tolerances established by this action.
EPAs assessment of exposures and risks associated with fluxametamide follows.
A. 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.
Fluxametamide belongs to a class of compounds called isoxazolines, which are potent inhibitors of g-aminobutyric acid GABA-, glutamate-, and glycinegated chloride channels in insects.
However, this pesticidal mode of action MOA does not seem to be operative in mammals as neurotoxicity was not found in either the acute or subchronic neurotoxicity studies at the limit dose.
The available studies show different organs can be affected. For the dietary toxicity studies in rats neurotoxicity study, chronic/carcinogenicity, and reproductive toxicity studies, a common effect on the gastrointestinal GI tract was observed. The effects consisted of gross pathology an increase incidence of abnormally pale color duodenum and jejunum and histopathology increased incidence of enterocyte epithelial vacuolation of the jejunum. Most of the effects seen in the subchronic neurotoxicity study were reproduced in the combined chronic and carcinogenicity study with increased severity and at lower dose level. In addition, consistent adverse effects were found in the lung aggregate alveolar marcophages and cholesterol cleft and liver centrilobular hepatocellular vacuolation and periportal hepatocellular vacuolation.
These adverse effects were present at a dose as low as 9 mg/kg/day in the carcinogenicity study.
Fluxametamide is classified as having suggestive evidence of carcinogenic
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potential based on thyroid tumors in male rats and liver tumors in male mice.
The reasons for this classification are 1
both tumor types are driven by adenomas, 2 these increased tumor incidences are seen at the highest doses tested 877 mg/kg/day for male mice and 899 mg/kg/day for male rats; these doses are approaching the limit dose 1000 mg/kg/day for a carcinogenicity study, 3 there is no hyperplasia of the liver in either male or female mice, 4
no increase in treatment-related tumors has been observed in female mice or female rats, and 5 no genotoxicity is observed in the required battery of mutagenic studies. Due to the lack of genotoxicity and the fact that the tumors are seen only at doses more than 100fold above the chronic reference dose, EPA has determined that a non-linear approach relying on the chronic reference dose RfD will adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to fluxametamide.
The in-utero and perinatal treatment with fluxametamide in rats resulted in toxicity and increased quantitative susceptibility in developing animals. In the 2-generation reproduction study, fluxametamide produced no parental effect at the highest dose tested 19 mg/
kg/day, while at the same dose level produced offspring effect which consisted of the observation that the pups had distended abdomens and affected pups had to be sacrificed for humane reason. The dermal toxicity study did not show systemic toxicity at the limit dose 1000 mg/kg/day.
Specific information on the studies received and the nature of the adverse effects caused by fluxametamide, as well as the no-observed-adverse-effectlevel NOAEL and the lowest-observedadverse-effect-level LOAEL from the toxicity studies, can be found at http:/
www.regulations.gov in document titled Fluxametamide: Human Health Risk Assessment to Support the Establishment of a Tolerance without U.S. Registration in/on Tea. First Food Use hereinafter Fluxametamide Human Health Risk Assessment at pages 1622 in docket ID number EPA
HQOPP20190492.
B. Toxicological Points of Departure/
Levels of Concern Once a pesticides 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
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