In Vivo Assessment of an Equimolar or Environmentally Relevant Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) Mixture

NIH RePORTER · NIH · N01 · $2,228,674 · view on reporter.nih.gov ↗

Abstract

The DTT has a variety of completed and ongoing studies related to PFAS. Notably, seven PFAS (PFNA, PFBS, PFHxA, PFDA, PFBS, PFOS, PFOA, PFHxS) were evaluated in 28-day toxicity studies using male and female rats to compare the toxicity of short- and long-chain carboxylates (n = 4) and sulfonates (n = 3). The main findings from these studies were effects on the thyroid (e.g., decreased free thyroxine) and liver (e.g., increased liver weight). The calculated relative potencies were used in calculation of the doses for this study. The DTT has also completed multiple other studies, including 2-year toxicity and carcinogenicity studies; however, in all the studies that have evaluated PFAS individually, none have assessed the effect of the joint action of exposure to multiple PFAS.  Human exposure data demonstrate that humans are exposed to PFAS mixtures, and epidemiological and animal data show that exposure to PFAS chemicals has dose-dependent adverse effects on multiple systems. Yet, the scientific basis for evaluating cumulative risk from exposure to PFAS mixtures is inadequate as it assumes that PFAS are dose additive and do not display greater-than-additive interactions, but these assumptions have not been tested. Due to the difference in toxicokinetics between males and females, and the different systems of the target effects, dose addition may not sufficiently predict the effect of the mixture. Thus, there is a critical need to address the questions outlined above and build a foundation for evaluating additional PFAS and PFAS mixtures in the future.

Key facts

NIH application ID
11216053
Project number
75N96024C00005-0-9999-3
Recipient
BATTELLE CENTERS/PUB HLTH RES & EVALUATN
Principal Investigator
DAWN FALLACARA
Activity code
N01
Funding institute
NIH
Fiscal year
2024
Award amount
$2,228,674
Award type
Project period
2024-09-16 → 2025-09-15