Cumulative assessment approaches: Laboratory research informing multiple chemical exposures

Due to the pervasive detection of multiple compounds such as PFAS and phthalates in human and environmental matrices, many health-based agencies are employing or pursuing cumulative assessment and regulatory approaches.  We have conducted many phthalate mixture studies and some of the only in vivo PFAS mixture studies investigating maternal and neonatal effects from maternal exposure during pregnancy in a rat model.  Experimental data were compared to predictions using established mixtures toxicology approaches and effects were well predicted using dose addition methods.  This presentation broadly discusses mixtures research and highlights the two most recent mixtures publications from our research group.

Impact/Purpose

Numerous mixtures studies from our group have demonstrated the accuracy of dose addition modeling for estimating combined effects on male reproductive tract development from exposure to multiple phthalates.  Our most recent publication demonstrated that these effects occur below individual chemical no effect levels when combined in a mixture.  Similarly, we recently published the first mammalian in vivo PFAS mixture study demonstrating dose additivity of a range of maternal and neonatal adverse effects from exposure during pregnancy.  These studies are highly informative for risk assessors and regulators when evaluating groups of compounds with similar toxicity and multi-contaminant exposures.     The studies described here are some of the only mammalian in vivo mixture toxicity studies of phthalates and of PFAS that incorporate mixture modeling and analyses to characterize the type of mixture effects and the accuracy of predictions using well-established approaches.  The results directly support the proposed approaches by the OW and OPPT, as well as state and international health-based agencies that have adopted mixture-based risk assessment and regulatory approaches for exposure to multiple phthalates or PFAS.

Citation

Conley, J. Cumulative assessment approaches: Laboratory research informing multiple chemical exposures. Duke University ITEHP Spring 2023 Symposium, Durham, NC, February 17, 2023.