PFAS in vitro (mixture) effects

PFASGrafiken

We apply high-throughput screening (HTS) and quantitative in vitro to in vivo extrapolation (QIVIVE) to evaluate and predict the toxicity of per- and polyfluoroalkyl substances (PFAS). Baseline toxicity, caused by chemical accumulation in cell membranes, was used as a reference to differentiate specific versus non-specific responses. Liposome-water distribution ratios and protein binding constants can be used to predict baseline toxicity for anionic and neutral PFAS. While PFAS like HFPO-DA showed high specificity for pathways like PPAR activation, most exhibited low specificity across other assays. Non-specific effects, particularly from hydrophobic PFAS, were additive in mixtures at environmentally relevant concentration ratios, emphasizing their toxicological relevance.

Using solid-phase microextraction (SPME), the free concentrations can be quantified in plasma, media, and cells across a wide concentration range. Protein-binding isotherms are nonlinear with freely dissolved concentrations varying significantly between bioassays and human plasma. A mass-balance model can be used to predict PFAS binding to blood and medium proteins and due to the large concentration gap between occurrence and toxicity the bioavailable fraction of PFAS might differ by orders of magnitude between blood and bioassays, which has important implications for QIVIVE

Persistent and low-potency PFAS raise concerns about chronic exposure risks. The findings stress the need for combining bioassays with advanced predictive models to assess cumulative toxicity in PFAS mixtures.
 

More information: 

Qin, W.; Henneberger, L.; Glüge, J.; König, M.; Escher, B. I., Baseline Toxicity Model to Identify the Specific and Nonspecific Effects of Per- and Polyfluoroalkyl Substances in Cell-Based Bioassays. Environ. Sci. Technol. 2024, 58, 5727-5738; DOI 10.1021/acs.est.3c09950.

Qin, W.; Henneberger, L.; Huchthausen, J.; König, M.; Escher, B. I., Role of bioavailability and protein binding of four anionic perfluoroalkyl substances in cell-based bioassays for quantitative in vitro to in vivo extrapolations. Environ. Internat. 2023, 173, 107857; DOI 10.1016/j.envint.2023.107857

Ríos-Bonilla, K. M.; Aga, D. S.; Lee, J.; König, M.; Qin, W.; Cristobal, J. R.; Atilla-Gokcumen, G. E.; Escher, B. I., Neurotoxic Effects of Mixtures of Perfluoroalkyl Substances (PFAS) at Environmental and Human Blood Concentrations. Environ. Sci. Technol. 2024, 58, 16774-16784; DOI 10.1021/acs.est.4c06017.