Voglio sapere a riguardo di…

Federal Register / Vol. 86, No. 42 / Friday, March 5, 2021 / Rules and Regulations
jbell on DSKJLSW7X2PROD with RULES

Subchronic studies in rats were performed for the numerous plant metabolites generated from parent picarbutrazox. All were less toxic than the parent molecule. No signs of neurotoxicity were observed in the acute neurotoxicity study up to the limit dose 2,000 mg/kg/day. No dermal toxicity was observed in rats up to the limit dose 1,000 mg/kg/day.
Picarbutrazox is categorized as having low acute lethality through the oral, dermal, and inhalation routes. It is minimally irritating to the eye and is neither a dermal irritant nor sensitizer.
In accordance with the EPAs Final Guidelines for Carcinogen Risk Assessment March 2005, the Agency classified picarbutrazox as Suggestive Evidence of Carcinogenic Potential based on an increase in the incidence of thyroid follicular cell tumors, driven by adenomas in male and female rats and combined thyroid follicular adenomas/
carcinomas in male rats. There is no concern for genotoxicity or mutagenicity and no treatment-related tumors were observed in mice. Based on its weightof-evidence analysis, the Agency has determined that quantification of risk using a non-linear approach i.e., chronic reference dose cRfD will adequately account for all chronic toxicity, including potential carcinogenicity, that could result from exposure to picarbutrazox. The chronic reference dose is several times lower than the dose at which tumors were observed.
Specific information on the studies received and the nature of the adverse effects caused by picarbutrazox 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 Picarbutrazox. Human Health Risk Assessment in Support of a New Active Ingredient for Use on Corn and Soybean Seed and Turf, dated December 18, 2020, hereinafter Picarbutrazox Human Health Risk Assessment in docket ID
number EPAHQOPP20170653.
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
VerDate Sep<11>2014

15:52 Mar 04, 2021

Jkt 253001

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 picarbutrazox used for human risk assessment can be found on pages 1920 in the Picarbutrazox Human Health Risk Assessment.
C. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to picarbutrazox, EPA
considered exposure under the petitioned-for tolerances. EPA assessed dietary exposures from picarbutrazox 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 picarbutrazox; therefore, a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the United States Department of Agricultures USDAs National Health and Nutrition Examination Survey, What We Eat in America, NHANES/
WWEIA. As to residue levels in food, EPA conducted an unrefined chronic dietary exposure assessment using tolerance-level residues, 100 percent crop treated PCT, and default processing factors.
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 picarbutrazox.
Quantification of risk using a non-linear approach i.e., cRfD will adequately
PO 00000

Frm 00033

Fmt 4700

Sfmt 4700

12831

account for all chronic toxicity, including potential carcinogenicity, that could result from exposure to picarbutrazox.
iv. Anticipated residue and percent crop treated PCT information. EPA did not use anticipated residue and/or PCT
information in the dietary assessment for picarbutrazox. Tolerance level residues and/or 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for picarbutrazox in drinking water.
These simulation models take into account data on the physical, chemical, and fate/transport characteristics of picarbutrazox. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http www2.epa.gov/
pesticide-science-and-assessingpesticide-risks/about-water-exposuremodels-used-pesticide.
Using the Pesticides in Water Calculator PWC ver. 1.52, EPA
calculated the estimated drinking water concentrations EDWCs of picarbutrazox for chronic exposures in surface and ground water. The groundwater estimates were significantly lower. EPA used the modeled EDWC of 2.56 ppb directly in dietary exposure model to account for the contribution of picarbutrazox residues in drinking water for the chronic dietary risk assessment.
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.
Picarbutrazox is currently proposed for turf uses that could result in residential exposures. EPA assessed residential exposure using the following assumptions: There is the potential for post-application exposure for adults and children following turf treatments made by professional applicators with picarbutrazox. A dermal exposure assessment was not quantitatively conducted because a dermal POD was not selected. The quantitative exposure/
risk assessment for residential postapplication exposures is based only on incidental oral scenarios for children 1
to <2 years old from hand to mouth activities on treated turf. Postapplication exposure and risk estimates indicate that the short-term incidental oral MOEs, ranging from 970 to 360,000, are not of concern i.e., MOEs 30.
Further information regarding EPA
standard assumptions and generic
E:FRFM05MRR1.SGM

05MRR1