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Federal Register / Vol. 86, No. 228 / Wednesday, December 1, 2021 / Rules and Regulations <2 years old contacting treated turf dermal and incidental oral exposure at the 0.23 lb ai/A rate; children 6 to <11
years old contacting treated gardens dermal exposure; and children 11 to 16 years old golfing on treated turf dermal exposure.
Further information regarding EPA
standard assumptions and generic inputs for residential exposures may be found at http www2.epa.gov/pesticidescience-and-assessing-pesticide-risks/
standard-operating-proceduresresidential-pesticide.
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.
The Agency has determined that the pyrethroids and pyrethrins share a common mechanism of toxicity http
www.regulations.gov; EPAHQOPP
200804890006. As explained in that document, the members of this group share the ability to interact with voltagegated sodium channels ultimately leading to neurotoxicity. In 2011, after establishing a common mechanism grouping for the pyrethroids and pyrethrins, the Agency conducted a cumulative risk assessment CRA
which is available at http
www.regulations.gov; EPAHQOPP
20110746. In that document, the Agency concluded that cumulative exposures to pyrethroids based on pesticidal uses registered at the time the assessment was conducted did not present risks of concern. For information regarding EPAs efforts to evaluate the risk of exposure to this class of chemicals, refer to https
www.epa.gov/ingredients-usedpesticide-products/pyrethrins-andpyrethroids.
Since the 2011 CRA, for each new pyrethroid and pyrethrin use, the Agency has conducted a screen to evaluate any potential impacts on the CRA prior to registration of that use. A
new turf use for the pyrethroid, taufluvalinate, was assessed after completion of the cumulative, which did impact the worst-case non-dietary risk estimates identified in the 2011
CRA for the turf scenario Memo, DeLeon, H., D450820, 12/16/2019.
However, the overall finding i.e., that the pyrethroid cumulative risk is below the Agencys level of concern did not change upon registration of this new use.

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To account for the additional uses requiring tolerances in this rule, the Agency has conducted an additional screen, taking into account all previously approved uses and these proposed new uses. The additional uses will not significantly impact the cumulative assessment because dietary exposures make a minor contribution to total pyrethroid exposure relative to residential exposures in the 2011
cumulative risk assessment. Therefore, the results of the 2011 CRA are still valid and there are no cumulative risks of concern for the pyrethroids/
pyrethrins.
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 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.
Bifenthrin has been evaluated for potential developmental effects in the rat following gavage and dietary administration and in the rabbit gavage administration. Maternal toxicity included neurological effects tremors in rats and rabbits; head and forelimb twitching in rabbits. There were no developmental effects of biological significance in either species. The registrant submitted a Developmental Neurotoxicity DNT study, which establishes a clear NOAEL for the adult and offspring toxicity. The NOAEL in adults and offspring is similar in magnitude, and the LOAELs are based on the clinical signs of neurotoxicity dams had tremors and convulsions, offspring had increased grooming counts. Based on targeted testing in the DNT study for common endpoints for bifenthrin, there was no increase in sensitivity in rat pups. However, the Agency has reviewed existing pyrethroid data and concludes that the DNT is not a particularly sensitive study for comparing the sensitivity of young and adult animals to pyrethroids. Some literature studies indicated susceptibility for other pyrethroids, but in context, these studies were
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conducted at relatively high doses, which may not reflect environmental exposures. The reproductive toxicity of bifenthrin was examined in a 2generation reproduction dietary study in the rat. Tremors were noted only in females of both generations, with one parental generation rat observed to have clonic convulsions, and no observed effects in the offspring. Overall, there is no indication of increased juvenile sensitivity specifically to bifenthrin.
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 bifenthrin is complete.
ii. Like other pyrethroids, bifenthrin causes clinical signs of neurotoxicity from interaction with sodium channels.
These effects are adequately assessed by the available guideline and nonguideline studies. Bifenthrin is a Type I pyrethroid, and neurotoxic effects characteristic of Type I pyrethroids were observed in adults in most of the bifenthrin toxicity database.
Specifically, muscle tremors and decreased motor activity were observed in adults in guideline studies throughout the bifenthrin toxicology database, and hind-limb flexion was observed in adults the dermal study. For these reasons, the tremors seen in juveniles in the 2-generation reproduction study are not considered age-dependent effects.
iii. There was no evidence that bifenthrin resulted in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study. Previously, however, EPA retained a FQPA safety factor of 3X to account for concerns about pharmacokinetic PK differences between adults and children. The Agency has re-evaluated the need for an FQPA Safety Factor for human health risk assessments for pyrethroid pesticides based on a review of the available guideline and literature studies as well as data from the Council for the Advancement of Pyrethroid Human Risk Assessment CAPHRA
program. That recent data, including human physiologically based pharmacokinetic PBPK models as well as in vivo and in vitro data on protein binding, enzyme ontogeny, and metabolic clearance, support the conclusion that the PK contribution to the FQPA safety factor can be reduced to 1X for all populations.
iv. There are no residual uncertainties identified in the exposure databases.

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