Quiero saber acerca de...

Federal Register / Vol. 86, No. 231 / Monday, December 6, 2021 / Rules and Regulations Isoprothiolane is classified as Suggestive Evidence of Carcinogenic Potential based upon increases of skin keratoacanthomas and keratoacanthomas, papillomas, basal cell epitheliomas and/or squamous cell carcinomas combined in male rats.
Isoprothiolane is not considered to be genotoxic. The Agency has determined that quantification of risk using a nonlinear approach i.e., chronic reference dose cRfD will adequately account for all chronic toxicity, including any potential carcinogenicity, that could result from exposure to isoprothiolane.
Specific information on the studies received and the nature of the adverse effects caused by isoprothiolane 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 https
www.regulations.gov in document Isoprothiolane. Human Health Risk Assessment for Isoprothiolane Tolerances for Banana and Rice without a U.S. Registration First Food Use hereinafter Isoprothiolane Human Health Risk Assessment at pages 2344
in docket ID number EPAHQOPP
20200424.

khammond on DSKJM1Z7X2PROD with RULES

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 information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see https www2.epa.gov/
pesticide-science-and-assessing-

VerDate Sep<11>2014

15:44 Dec 03, 2021

Jkt 256001

pesticide-risks/assessing-human-healthrisk-pesticide.
A summary of the toxicological endpoints for isoprothiolane used for human risk assessment can be found in the Isoprothiolane Human Health Risk Assessment.
C. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to isoprothiolane, EPA
considered exposure under the petitioned-for tolerances. EPA assessed dietary exposures from isoprothiolane 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 isoprothiolane; therefore, a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the 20032008 food consumption data from the U.S.
Department of Agricultures USDAs National Health and Nutrition Examination Survey, What We Eat in America NHANES/WWEIA. As to residue levels in food, EPA assumed tolerance-level residues or tolerance level residues adjusted to account for the residue of concern for risk assessment; default and empirical processing factors; and 100 percent crop treated PCT.
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. Cancer risk is quantified using a linear or nonlinear approach. If sufficient information on the carcinogenic mode of action is available, a threshold or nonlinear approach is used and a cancer RfD is calculated based on an earlier noncancer key event.
If carcinogenic mode of action data are not available, or if the mode of action data determines a mutagenic mode of action, a default linear cancer slope factor approach is utilized. Based on its review of available data, EPA has concluded that a nonlinear RfD
approach will adequately account for all chronic toxicity, including any potential carcinogenicity, that could result from exposure to isoprothiolane. Cancer risk was assessed using the same exposure estimates as discussed in Unit III.C.1.ii., chronic exposure.

PO 00000

Frm 00049

Fmt 4700

Sfmt 4700

68923

iv. Percent crop treated PCT
information. EPA did not use anticipated residue and/or PCT
information in the dietary assessment for isoprothiolane. Tolerance level residues and/or 100% CT were assumed for all food commodities.
2. Dietary exposure from drinking water. Residues are not expected in drinking water as the products will not be used in the U.S.
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.
Isoprothiolane is not registered for any use patterns; therefore, there is no 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 isoprothiolane and any other substances and isoprothiolane does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that isoprothiolane has a common mechanism of toxicity with other substances. For information regarding EPAs efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPAs website at https
www.epa.gov/pesticide-science-andassessing-pesticide-risks/pesticidecumulative-risk-assessment-framework.
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 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
E:FRFM06DER1.SGM

06DER1