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Federal Register / Vol. 86, No. 209 / Tuesday, November 2, 2021 / Rules and Regulations Gowan Company, P.O. Box 5569, Yuma, AZ 85364. The petition requested to amend the tolerance in 40 CFR 180.693
for residues of the herbicide benzobicyclon in or on rice to 0.15 parts per million ppm. That document referenced a summary of the petition prepared by Gowan, the petitioner, which is available in the docket, http
www.regulations.gov. There were no comments received in response to the notice of filing.

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III. Aggregate Risk Assessment and Determination of Safety Section 408b2Ai of FFDCA
allows EPA to establish a tolerance the legal limit for a pesticide chemical residue in or on a food only if EPA
determines that the tolerance is safe.
Section 408b2Aii of FFDCA
defines safe to mean that there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information. This includes exposure through drinking water and in residential settings but does not include occupational exposure. Section 408b2C of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue . . .
Consistent with FFDCA section 408b2D, and the factors specified therein, EPA has reviewed the available scientific data and other relevant information in support of this action.
EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure for benzobicyclon, including exposure resulting from the tolerance established by this action. EPAs assessment of exposures and risks associated with benzobicyclon follows.
In an effort to streamline its publications in the Federal Register, EPA is not reprinting sections that repeat what has been previously published for tolerance rulemaking of the same pesticide chemical. Where scientific information concerning a particular chemical remains unchanged, the content of those sections would not vary between tolerance rulemaking, and EPA considers referral back to those sections as sufficient to provide an explanation of the information EPA
considered in making its safety determination for the new rulemaking.

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EPA has previously published a tolerance rulemaking for benzobicyclon, in which EPA concluded, based on the available information, that there is a reasonable certainty that no harm would result from aggregate exposure to benzobicyclon and established a tolerance for residues of that chemical.
See the benzobicyclon tolerance rulemaking published in the Federal Register of April 25, 2017 82 FR 18995
FRL996102. EPA is incorporating previously published sections from that rulemaking that remain unchanged, as described further in this rulemaking.
Toxicological profile. There have been updates to the toxicological profile from the previous assessment. The parent compound, benzobicyclon, is a propesticide, which means it requires hydrolysis of the thiophenyl group to generate the anticipated pesticidal active moiety, metabolite B also referred to as 1315P070. The toxicological database is considered complete for risk assessment purposes for both the parent, benzobicyclon, and metabolite B. The enzyme 4hydroxyphenylpyruvate dioxygenase HPPD is involved in the catabolism of tyrosine, an essential amino acid for mammals. While benzobicyclon may be referred to as an HPPD inhibitor, typical HPPD-inhibiting effects are not observed in its toxicological database. However, metabolite B does exhibit HPPDinhibiting effects and is therefore considered an HPPD-inhibiting chemical. The initiating event in the mode-of-action MOA/adverse-outcome pathway AOP for HPPD-inhibiting chemicals, including metabolite B, involves binding of the chemical to the HPPD enzyme causing complete or virtually complete enzyme inhibition, which leads to a build-up of systemic tyrosine levels tyrosinemia and a spectrum of tyrosine-mediated effects.
In laboratory animals, these have been identified as ocular and skeletal developmental effects. Species differences exist in laboratory animals related to the ability of a species to clear excess tyrosine from its system, which can impact its sensitivity to HPPDinhibiting chemicals and its relevance for human health risk assessment. In this risk assessment, endpoints were selected for both benzobicyclon and metabolite B. Taking into account species differences, endpoints for human health risk assessment of HPPD
inhibitors, including metabolite B, were selected from studies available in mice and dogs. Studies from other HPPD
inhibitors were used for bridging to metabolite B as needed. Since benzobicyclon does not exhibit HPPD-

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inhibiting properties, endpoints were selected from the most sensitive species and effects in its database not restricted to mice and dogs.
Benzobicyclon: An acute dietary endpoint was not selected for benzobicyclon, as there were no effects attributable to a single dose identified in the database. The chronic dietary, incidental oral, and inhalation endpoints were based on increased incidence of hydropic degeneration basophilic cells in the pituitary observed in the two-generation reproduction toxicity study in rats. A
dermal endpoint was not selected since no hazard was identified in the dermal toxicity study and there was no evidence of increased quantitative susceptibility in the database.
Benzobicyclon is classified as Not Likely to be Carcinogenic to Humans based on the absence of treatmentrelated tumors in two adequate rodent carcinogenicity studies.
Metabolite B: There were no effects attributable to a single dose available in the metabolite B database or in studies from other HPPD inhibitors; therefore, an acute dietary endpoint was not selected for metabolite B. The chronic dietary endpoint is based on gallstones, eosinophilic cytoplasmic alteration, subepithelial mixed cell infiltrate, and dilatation in/of the gallbladder;
hepatocellular vacuolation, hepatocellular hypertrophy, and increased liver weight in males and females; and papillary mineralization of the kidney and changes in hematological parameters indicative of anemia in females observed in the chronic/carcinogenicity study in mice from another HPPD chemical available for bridging tembotrione. Since the only anticipated exposure is through drinking water, no additional points of departure PODs were selected for metabolite B. There are no carcinogenicity studies available for metabolite B; however, carcinogenicity studies are available for bridging for all of the other currently registered HPPD
inhibitors. Overall, potential carcinogenicity is not a concern for the HPPD inhibitors, and the chronic dietary endpoint and POD for metabolite B is considered protective of any potential carcinogenicity.
Additional information is available in the docket for this action in the document titled Benzobicyclon:
Section 3 Risk Assessment for Proposed New Formulation, Increase to the Established Tolerance, and National Use Expansion on Rice hereafter, the Benzobicyclon Human Health Risk Assessment.

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