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Federal Register / Vol. 86, No. 44 / Tuesday, March 9, 2021 / Rules and Regulations subgroups of consumers, including infants and children.
The target organs of fluindapyr are the liver and thyroid. Liver effects include hepatocellular hypertrophy, increased liver weights, and bile duct hyperplasia with correlated increases in alkaline phosphatase ALP, alanine aminotransferase ALT, and gamma glutamyl transferase GGT at the highest dose tested. Liver effects progress with time in treated dogs, while similar effects are not seen in rats and mice at high dose levels. Liver effects are seen in the mouse carcinogenicity study at a higher dose level than the liver effects observed in dogs; the effects consisted of increased incidence of hepatocellular alterations basophilic, eosinophilic, vacuolated, necrosis, and pigmented macrophages.
Thyroid effects include increased instances of follicular hypertrophy/
hyperplasia.
In the acute neurotoxicity study, potential evidence of neurotoxicity in the form of decreases in total and ambulatory motor activities and in rearing were seen in the rat. However, no additional functional observation FOB parameters were affected, and no neuropathological findings of both central and peripheral nerves were observed.
There is no evidence of increased quantitative or qualitative susceptibility in the developmental toxicity studies in rabbits or rats; or the reproductive toxicity study in rats. With in-utero exposure in the developmental toxicity studies, fluindapyr did not produce any adverse effects in either rat or rabbit parental animals or fetuses at or approaching the limit dose. In the reproduction study, in parental animals P and F1 males and females, fluindapyr induced an increase in thyroid follicular hypertrophy/
hyperplasia. It also induced adverse effects on a host of reproductive parameters. It also produced adverse offspring effects as indicated by decreases in F1 and F2 pup body weights in both sexes; thymus and spleen weights were also decreased. The parental, reproductive, and offspring effects all occurred at the same dose levels. The increased incidence of thyroid follicular hypertrophy/
hyperplasia raised concerns for the potential of thyroid effects on the developing animals. EPA applied a 10X
safety factor to the appropriate exposure scenarios to account for the uncertainties associated with the life stage susceptibility.
In the chronic toxicity/carcinogenicity studies in rats and mice, there was no evidence of carcinogenicity. The
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mutagenicity battery was negative.
Fluindapyr is classified as Not Likely to be Carcinogenic to Humans.
Specific information on the studies received and the nature of the adverse effects caused by fluindapyr as well as the no-observed-adverse-effect-level NOAEL and the lowest-observedadverse-effect-level LOAEL from the toxicity studies can be found at http
www.regulations.gov in document Fluindapyr: Human Health Risk Assessment for Section 3 Registration and Tolerance Requests for a New Active Ingredient Proposed for Use on Cereal Grains Crop Group 15 except Rice; Forage, Fodder and Straw of Cereal Grains Crop Group 16; and Soybean hereinafter Fluindapyr Human Health Risk Assessment on pages 1420 in docket ID number EPA
HQOPP20180551.
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 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 levelgenerally referred to as a population-adjusted dose PAD or a reference dose RfDand 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
www2.epa.gov/pesticide-science-andassessing-pesticide-risks/assessinghuman-health-risk-pesticide.
A summary of the toxicological endpoints for fluindapyr used for human risk assessment can be found in the Fluindapyr Human Health Risk Assessment.

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C. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to fluindapyr, EPA considered exposure under the petitioned-for tolerances. EPA assessed dietary exposures from fluindapyr 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 fluindapyr. In estimating acute dietary exposure, EPA used 20032008
food consumption information from the United States Department of Agriculture USDA Nationwide Health and Nutrition Examination Survey, What We Eat in America NHANES/WWEIA. As to residue levels in food, the acute analysis assumed 100% crop treated PCT for all commodities, highest average field trial HAFT residue values, empirical and default processing factors, and anticipated livestock residues based on calculated livestock dietary burden and tissue transfer rates from the livestock feeding studies.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used 20032008 food consumption data from the USDAs NHANES/
WWEIA. As to residue levels in food, chronic analysis assumed 100 PCT for all commodities, field trial mean residue values, empirical and default processing factors, and anticipated livestock residues based on calculated livestock dietary burden and tissue transfer rates from the livestock feeding studies and metabolite ratios from the metabolism studies.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that fluindapyr 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. Section 408b2E of FFDCA authorizes EPA
to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide residues that have been measured in food. If EPA relies on such information, EPA must require pursuant to FFDCA section 408f1
that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. For the present action, EPA
will issue such data call-ins as are required by FFDCA section 408b2E

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