Work

PFAS and heavy metals mixture in vitro: Insights into synergistic toxicity across multiple cell lines

Year: 2025

Type: article

Abstract: Poly- and perfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants originating from industrial processes. While the individual toxicities of PFAS and heavy metals have been extensively studied, their co-occurrence in the environment raises concerns on potential interactions that may amplify their effects on human health. Specifically, the manner in which heavy metals influence PFAS absorption, bioavailability, and combined toxicity remain poorly understood. This knowledge gap limits our ability to assess the true health risks associated with real-world co-exposures to these contaminants. To address this gap, our study investigates the mixture effects of PFAS and heavy metals on human cell viability, proliferation, migration, and DNA damage across five human cell lines (HepG2, A498, A549, A431, and PC3) at human-relevant exposure levels. In our study, 1 µM PFOA and GenX, along with 0.01 µM lead and arsenic, were chosen to represent human exposure levels. Our results revealed cell-type-specific responses, with mostly synergistic interactions observed across different cell lines. HepG2 and A549 cells exhibited impaired cell proliferation, increased DNA damage, and reduced cell migration upon mixture exposure, while A498 and PC3 cells showed increased cell proliferation, with less pronounced effects on DNA damage and migration. These findings suggest that PFAS and heavy metal mixtures can impact cellular functions through cell-type and combination-specific toxicological pathways. This study provides new insights into the complex interactions between PFAS and heavy metals, highlighting the need for further research to better understand the underlying mechanisms and its impact on health risks associated with co-exposure to these environmental contaminants.

Source: Journal of Hazardous Materials Advances

DOI: 10.1016/j.hazadv.2025.100913

Authors: Mia Sands, Arshveer Sachdeva, Laura Bukavina, Joseph Irudayaraj