Quiero saber acerca de...

jspears on DSK121TN23PROD with RULES1

60370

Federal Register / Vol. 86, No. 209 / Tuesday, November 2, 2021 / Rules and Regulations
Toxicological points of departure/
Levels of concern. For a summary of the Toxicological Points of Departure/
Levels of Concern for benzobicyclon and metabolite B used for human health risk assessment, please reference section 4.6.3 on pages 2527 of the Benzobicyclon Human Health Risk Assessment.
Exposure assessment. EPAs dietary exposure assessments have been updated to include the additional exposure from the tolerance increase on rice grain and national use expansion.
No effects attributable to a single dose were observed for benzobicyclon or metabolite B; therefore, acute dietary exposure assessments were not conducted.
Based on the toxicological effects of benzobicyclon and metabolite B, separate chronic dietary exposure and risk assessments were conducted. The assessments were conducted using Dietary Exposure Evaluation Model software with the Food Commodity Intake Database DEEMFCID Version 3.16, which uses food consumption data from the U.S. Department of Agricultures USDAs National Health and Nutrition Examination Survey, What We Eat in America, NHANES/
WWEIA. This dietary survey was conducted from 2003 to 2008.
The benzobicyclon chronic dietary exposure assessment assumed tolerancelevel residues for rice, 100 percent crop treated PCT, and a modeled estimated drinking water concentration EDWC of 0.199 parts per billion ppb. The DEEM
default processing factor of 1.25 was used for both rice flour and rice bran.
There is no anticipated exposure in food to metabolite B. As metabolite B is only a residue of concern in drinking water, the chronic dietary exposure assessment was conducted for drinking water only. The chronic analysis used a modeled EDWC of 4.27 ppb and assumed 100 PCT.
There are no residential nonoccupational exposures associated with benzobicyclon or metabolite B.
Cumulative exposure. The Agency is required to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. The Agency has determined that the p-hydroxyphenylpyruvate dioxygenase HPPD inhibitors share a common mechanism of toxicity as discussed in the document titled HPPD Inhibiting Herbicides: State of the Science, which is available in the docket for this action. As explained in that document, the members of this group of chemicals share the ability to bind to and inhibit the HPPD enzyme resulting in elevated systemic tyrosine levels and common apical outcomes
VerDate Sep<11>2014

15:50 Nov 01, 2021

Jkt 256001

that are mediated by tyrosine, including ocular and developmental effects. In 2021, after establishing a common mechanism grouping for the HPPD
inhibitors, the Agency conducted the P-Hydroxyphenyl-Pyruvate Dioxygenase HPPD Inhibitors Cumulative Risk Assessment:
Benzobicyclon, Bicyclopyrone, Isoxaflutole, Mesotrione, Pyrasulfotole, Tembotrione, Tolpyralate, and Topramezone, which is available in the docket for the action, and concluded that cumulative exposures to HPPD
inhibitors based on proposed and registered pesticidal uses at the time the assessment was conducted did not present risks of concern.
Safety Factor SF for Infants and Children. The Food Quality Protection Act FQPA section has been updated since the last assessment. EPA has determined that the required FQPA SF
of 10X for the protection of infants and children be reduced to 1X for all exposure scenarios for benzobicyclon parent. For metabolite B, since the chronic dietary endpoint is based on a study with no No-Observed-AdverseEffect Level NOAEL, a 10X FQPA SF/
Uncertainty Factor UFL has been retained for extrapolation from a Lowest-Observed-Adverse-Effect Level LOAEL to a NOAEL.
Completeness of the Toxicology Database: The existing toxicological database for benzobicyclon is adequate for FQPA evaluation. Developmental and two-generation reproduction studies in rats are available for benzobicyclon. However, the active moiety of benzobicyclon, metabolite B, has been shown to be more toxic than the parent compound. Therefore, studies were conducted with metabolite B, including a developmental toxicity study in mice. Additionally, 2generation reproduction toxicity studies are available from other HPPD inhibitors for bridging.
Evidence of Neurotoxicity: There was no neurotoxicity observed throughout the database for benzobicyclon or metabolite B. The subchronic neurotoxicity study with benzobicyclon tested up to 1,290 mg/kg with no adverse effects observed, nor was there evidence of neurotoxicity in any of the guideline studies in the databases for either chemical.
Evidence of Sensitivity/Susceptibility in the Developing or Young Animal: For benzobicyclon, there was no increased qualitative or quantitative susceptibility observed in the two-generation reproduction or developmental toxicity studies in rats. A developmental study in rabbits was submitted but was
PO 00000

Frm 00014

Fmt 4700

Sfmt 4700

considered unacceptable and subsequently waived by EPA.
For metabolite B, a developmental toxicity study in mice did not show any increased qualitative or quantitative susceptibility. A 2-generation reproduction study is not available for metabolite B; however, there are 2generation reproduction studies from other HPPDs inhibitors that can be used for bridging. In one of the 2-generation studies in mice for another HPPD
inhibitor mesotrione, quantitative susceptibility was observed in offspring.
However, concern is low because there are clear NOAEL/LOAEL values for the observed effects, the offspring LOAEL of 300 mg/kg/day from the mesotrione 2generation reproduction toxicity study was set conservatively based on a low incidence of opaque/cloudy eyes, and the selected endpoints used in this risk assessment are protective of any potential sensitivity observed in mice.
Residual Uncertainty in the Exposure Database: The exposure databases are complete or are estimated based on data that reasonably account for potential exposures. There are no registered or proposed residential uses and/or commercial uses at residential sites for benzobicyclon at this time. Therefore, a residential exposure assessment is not required. The dietary exposure assessments food and drinking water are considered to be conservative estimates of exposure. Tolerance-level residues for rice and 100 PCT were assumed for the food exposure assessment. Drinking water exposure estimates for both benzobicyclon and metabolite B are based on conservative models assuming maximum use rates and are not expected to underestimate the exposure. The Agency is confident that the assessments do not underestimate risk from dietary exposure to benzobicyclon or metabolite B.
Aggregate risks and Determination of safety. EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute population-adjusted dose aPAD and the chronic population-adjusted dose cPAD. Short-, intermediate-, and chronic term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate points of departure to ensure that an adequate margin of exposure MOE exists. For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure.
There are no acute dietary endpoints for benzobicyclon or metabolite B;
therefore, an acute risk assessment is
E:FRFM02NOR1.SGM

02NOR1