Evaluation of the FQPA Safety Factor for Pyrethrins and Pyrethroids

The Food Quality Protection Act (FQPA) requires EPA to consider the unique susceptibility of infants and children by applying an additional default safety factor when reviewing the safety of pesticides. The law also allows EPA to adjust this safety factor if the Agency has reliable data showing that a revised safety factor would still be protective of the health of infants and children.

EPA previously conducted a review of the literature and reduced the standard 10X to a 3X safety factor for pyrethroid pesticides. In 2019, EPA thoroughly reviewed newly available scientific literature and studies on pyrethroid pesticides and found the science demonstrates that the FQPA safety factor for pyrethroids can be reduced further from 3X to 1X and still be protective of infants and children.

The data provide strong scientific evidence that infants and children are not more sensitive than adults to pyrethroid pesticides. EPA is now soliciting comment on the white paper that explains EPA’s 2019 re-evaluation of the FQPA safety factor.

Read the white paper and supporting documents outlining EPA’s re-evaluation of the safety factor for pyrethroids. EPA will be accepting comments on this document until January 13, 2020, in docket # EPA-HQ-OPP-2008-0331 on www.regulations.gov.

More Information on the FQPA Safety Factor

FQPA requires EPA to apply an additional 10X margin of safety, or safety factor, to human health risk assessments to account for potential prenatal and postnatal toxicity for infants and children. The law allows a different margin of safety only if the Agency has reliable data supporting a conclusion that the revised safety factor would protect infants and children.

The Agency considers the default additional 10X FQPA safety factor to have two components: 3X assigned to pharmacokinetic (PK) differences and 3X for pharmacodynamic (PD) differences. The PK component refers to the process of chemicals being absorbed, distributed, metabolized and excreted from and in the body. The PD component refers to how a chemical affects the body’s tissue.

EPA’s review of new data provided strong scientific evidence that there is no PK difference between infants/children and adults, meaning the data demonstrate there is no increased sensitivity between adults and infants/children for pyrethroid pesticides. Therefore, the PK portion of the FQPA safety factor can be reduced from 3X to 1X.

EPA’s 2010 evaluation of data supported the reduction of the PD portion of the FQPA safety factor to 1X which remains unchanged.

Regulatory History

In 2009, EPA determined that developmental toxicity studies (DNTs) previously required for pyrethroid insecticides did not adequately characterize potential susceptibility of the young. In a Sep. 4, 2009, letter, we stated that registrants that had not already complied with DNT requirements could instead cite six previously submitted pyrethroid DNT studies rather than conduct a new study. We noted that other data may be needed to fully address the potential for increased susceptibility of young organisms to the pyrethroids, focusing on pyrethroid-specific effects related to the mode of action and pharmacokinetic characteristics of this class of compounds.

In a Feb. 16, 2010, letter to the registrant and stakeholder community, EPA asked companies and other interested parties to voluntarily submit study protocols designed to better understand the potential susceptibility associated with pyrethroids. We reviewed proposals submitted and presented them to the FIFRA Scientific Advisory Panel (SAP) for comment at their July 23, 2010, meeting on Comparative Adult and Juvenile Sensitivity Toxicity Protocols for Pyrethroids. View meeting information and minutes

In 2010, EPA developed a science paper that discussed the DNT study and related data issues.View Pyrethroids: Evaluation of Data from Developmental Neurotoxicity Studies and Consideration of Comparative Sensitivity.

• EPA letter to pyrethroid registrants (Sept. 4, 2009)
• EPA letter to pyrethroid registrants (Feb. 16, 2010)
• Pyrethroids: Evaluation of Data from Developmental Neurotoxicity Studies and Consideration of Comparative Sensitivity (Jan. 20, 2010)
• Re-Evaluation of the FQPA Safety Factor for Pyrethroid Pesticides (June 27, 2011) 

Based on feedback from the SAP and EPA, the industry research proposal was revised. The Council for the Advancement of Pyrethroid Human Health Risk Assessment (CAPHRA) worked with academic scientists to develop assays and models to assess the potential for juvenile post-natal sensitivity to pyrethroids. The CAPHRA presented their research at an SAP meeting on May 19, 2015. View meeting information and minutes in the docket.