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Federal Register / Vol. 86, No. 30 / Wednesday, February 17, 2021 / Rules and Regulations
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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 fluxametamide used for human risk assessment can be found in the Fluxametamide Human Health Risk Assessment.
C. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to fluxametamide, EPA
considered exposure under the petitioned-for tolerances. EPA assessed dietary exposures from fluxametamide 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. No such effects were identified in the toxicological studies for fluxametamide; therefore, a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used 20032008 food consumption data from the United States Department of Agricultures USDA National Health and Nutrition Examination Survey, What We Eat in America, NHANES/
WWEIA. As to residue levels in food, EPA assumed tolerance-level residues of fluxametamide on tea and 100% crop treated.
iii. Cancer. EPA determines whether quantitative cancer exposure and risk assessments are appropriate for a fooduse pesticide based on the weight of the evidence from cancer studies and other relevant data. Based on the data
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summarized in Unit III.A., EPA has concluded that a nonlinear RfD
approach will adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to fluxametimide. A separate cancer dietary exposure and risk assessment is not required. Cancer risk was assessed using the same exposure estimates as discussed in Unit III.C.1.ii., chronic exposure.
iv. Anticipated residue and percent crop treated PCT information. EPA did not use anticipated residue and/or PCT
information in the dietary assessment for fluxametamide. Tolerance level residues and/or 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. EPA assumes that there is no exposure through drinking water because fluxametamide is not registered for use in the United States. Because residues are not expected in drinking water, dietary risk estimates include exposures from food only.
3. From non-dietary exposure. The term residential exposure is used in this document to refer to nonoccupational, non-dietary exposure e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets.
Fluxametamide is not being proposed to be registered for any specific use patterns that would result in residential exposure.
4. Cumulative effects from substances with a common mechanism of toxicity.
Section 408b2Dv of FFDCA
requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider available information concerning the cumulative effects of a particular pesticides residues and other substances that have a common mechanism of toxicity.
Unlike other pesticides for which EPA
has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to fluxametamide and any other substances and fluxametamide does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA
has not assumed that fluxametamide has a common mechanism of toxicity with other substances.
D. Safety Factor for Infants and Children 1. In general. Section 408b2C of FFDCA provides that EPA shall apply an additional tenfold 10X margin of safety for infants and children in the case of threshold effects to account for
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prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the FQPA Safety Factor SF. In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor.
2. Prenatal and postnatal sensitivity.
There is an increase in quantitative susceptibility in two-generation reproductive toxicity study in rats. In this study, parental animals showed no adverse effects at 19 mg/kg/day highest dose tested, HDT, whereas some pups had to be euthanized due to distended abdomen at the same dose. However, the concern is low because there was a clear NOAEL for the offspring effect 6
mg/kg/day and the POD selected for chronic dietary exposure assessment 1
mg/kg/day is protective of the offspring effects seen in the reproductive toxicity study.
3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF
were reduced to 1X. That decision is based on the following findings:
i. The toxicity database for fluxametamide is complete.
ii. There is no indication that fluxametamide is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.
iii. There is evidence of an increase in quantitative susceptibility in the 2generation reproductive toxicity study in rats. In this study, parental animals showed no adverse effects at 19 mg/kg/
day highest dose tested, HDT, whereas some pups had to be euthanized due to distended abdomen at the same dose.
However, the concern is low because there was a clear NOAEL for the offspring effect 6 mg/kg/day and the POD selected for chronic dietary exposure assessment 1 mg/kg/day is protective of the offspring effects seen in the reproductive toxicity study. The selected points of departure for risk assessment are protective of the quantitative increase in susceptibility seen in the rat reproductive toxicity study, for which a clear NOAEL and LOAEL are established.
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. These
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