A mixture of PFOS and PFOA is more harmful than each chemical on its own

Assessing the effects of chemical mixtures instead of the individual chemicals provides a better reflection of the exposure. This is shown in an article from a study on the tumorigenic potential of PFOS/PFOA mixtures on breast cancer, performed by a research group at Stockholm University led by Mistra SafeChem researcher Oskar Karlsson.

We are constantly exposed to chemical mixtures in the environment, food, drinking water, drugs, and consumer products. With a few exceptions, chemical risk is often assessed based on the individual chemical, which could lead to under- or over-estimation of potential risks.

Conventional toxicology approaches have limitations when considering the large number of compounds that need toxicity assessment, particularly if mixture effects also should be evaluated.

Investigated the impact of PFOS/PFOA mixtures on breast cancer

Several epidemiological studies have linked exposure to per- and polyfluoroalkyl substances (PFAS) with an increased risk of breast cancer. However, the mechanisms by which these compounds may contribute to cancer development need to be further elucidated in experimental models.

– In this study, we used human epithelial breast cells to evaluate the tumorigenic potential of PFOS/PFOA mixtures, Oskar Karlsson says.

The results revealed that very low concentrations (500 pM) of the binary PFOS and PFOA mixture induced synergistic effects on cell proliferation and caused neoplastic transformation of the cells.

Assessing by high-content imaging assay cell painting

The research group then established the novel high-content imaging assay cell painting to assess mixture effects on breast cell morphology. This assay multiplexes six fluorescent dyes that stain several cellular compartments and organelles, which allows detailed morphological profiling.

– Interestingly, hundreds of cell features were shown to be affected by the PFAS mixture even at the lowest concentration tested, which was 100 pM, Oskar Karlsson comments.

Shows potential involvement of PFOS/PFOA mixtures

Exposure to higher concentrations (≥50 µM) of the PFOS and PFOA mixture caused cell death through synergistic interactions that induced oxidative stress, DNA/RNA damage, and lipid peroxidation, illustrating the complexity of mixture toxicology.

– Our findings support the potential involvement of PFOS/PFOA mixtures in the cause of breast cancer. It also shows the power of image-based high-content screening for the development of new approach methodologies in toxicology, says Oskar Karlsson.

Read the article in Environment International: High-content analysis shows synergistic effects of low perfluorooctanoic acid (PFOS) and perfluorooctane sulfonic acid (PFOA) mixture concentrations on human breast epithelial cell carcinogenesis External link, opens in new window..

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