Extensive analysis of pollutant interactions: Identification of deleterious synergistic effects at environmentally relevant dose levels using Drosophila and mammalian cells

Environmental pollutants are commonly present in low concentrations, often as complex mixtures that can lead to various interaction phenomena, including synergism, antagonism, or additive effects. These interactions can alter the overall toxicity or biological impact of the mixture when compared to the effects of individual pollutants. While regulatory agencies typically assess the safety of individual pollutants, the cumulative and interactive effects of pollutant mixtures are less well understood. This study aims to address this gap by evaluating the interactions of eight common pollutants (BPA, BADGE, DBP, DEHP, PFOA, 4MBC, OMC, TCEP) at their no observed effect level (NOEL) concentrations. The study specifically focuses on identifying potential synergistic effects on cell viability, transcriptomic changes, and phenotypic outcomes in two biological models: Drosophila and mammalian cell lines. Nearly 400 combinations of pollutants were tested, and their effects were compared to those of individual pollutants and appropriate controls. The results highlighted significant findings, including detrimental effects of the BPA-DBP-OMC mixture on neuronal differentiation and the BADGE-OMC-TCEP mixture's negative impact on muscle differentiation on Drosophila and mammalian cell lines. Cytotoxic synergy effects were also found between bisphenol derivatives and phthalates. These findings emphasize the need to consider the risks associated with pollutant mixtures.