In vitro profiling of the potential endocrine disrupting activities affecting steroid and aryl hydrocarbon receptors of compounds and mixtures prevalent in human drinking water resources

Prioritizing chemicals posing threats to drinking water resources is crucial for legislation considering the cost of water treatment, remediation, and monitoring. We profiled in vitro potential endocrine disrupting activities (both agonistic and antagonistic) of 18 contaminants most prevalent in Walloon raw water resources intended for drinking water production, including several compound groups: pesticides, perfluorinated compounds, polycyclic aromatic hydrocarbons, a corrosion inhibitor, and bisphenol A. Mixtures thereof relevant for human realistic exposure were also investigated. Seven luciferase reporter gene cell lines were used i.e. three (human and rat) responsive to dioxins through the aryl hydrocarbon receptor (AhR) and four (human) responsive to steroids through the estrogen (ER), androgen (AR), progesterone (PR), and glucocorticoid (GR) receptors. Among the 18 compounds, ten caused at least one response in at least one receptor. Specifically, chlorpyrifos, bisphenol A, fluoranthene, phenanthrene, and benzo [a]pyrene displayed significant activities on several receptors. Bisphenol A agonized ER, but abolished the cells’ response to androgen and progesterone. While fluoranthene and phenanthrene strongly reduced human AhR and AR transactivation, benzo [a]pyrene strongly activated AhR and ER, but inhibited GR and AR. In human breast cancer cells, benzo [a]pyrene dramatically activated AhR, inducing a 10-fold higher response than 2,3,7,8-tetrachlorodibenzodioxin (TCDD) at concentrations possibly found realistically in human blood. The mixture of the 18 compounds exerted both ER and rat AhR agonism, with the main contribution being from benzo [a]pyrene or its combination with bisphenol A. Moreover, the mixture significantly inhibited TCDD-induced CYP1A activity (detected only by EROD assays) in human hepatoma cells.