EPA report on use of NAMs for human health risk assessment
New approach methodologies (NAMs) can provide human-relevant information that may be challenging to obtain from whole-animal tests. EPA’s Office of Pesticide Programs is interested in using NAMs to reduce the reliance on default assumptions for risk assessment, including the application of 10X default uncertainty factors each for interspecies and intraspecies extrapolations. To this end, the Office of Pesticide Programs collaborated with EPA’s Office of Research and Development, academia, and industry to use NAM data to inform extrapolation/uncertainty and safety factors. As a part of this effort, EPA held a public meeting of the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel in September 2020 to consider and review the use of NAMs to derive extrapolation factors and evaluate developmental neurotoxicity (DNT) for human health risk assessment. The panel was supportive of using the DNT NAM battery in weight-of-evidence evaluations of DNT potential, while recognizing that the battery should be a “living and evolving process.” The panel also supported the use of chemical-specific in vitro data to inform interspecies extrapolation factors for organophosphate pesticides, but provided recommendations to reanalyze the data in a manner more consistent with the EPA’s “Guidance for Applying Quantitative Data to Develop Data-Derived Extrapolation Factors.” EPA responded to the panel’s recommendations in a March 2023 memorandum, available with related documents on the Regulations.gov website.