Chemical Mixtures in Household Environments: In Silico Predictions and In Vitro Testing of Potential Joint Toxicities in Human Liver Cells

There are thousands of chemicals that humans can be exposed to in their everyday environments, the majority of which remain understudied and lack substantial testing for potential exposure and toxicity. This study aimed to implement in silico methods to characterize chemicals that co-occur across chemical and product uses in our everyday household environments that also target a common molecular mediator, thus representing understudied mixtures that may exacerbate toxicity in humans. To detail, the Chemical and Products Database (CPDat) was queried to identify which chemicals co-occur across common exposure sources. Chemicals were pre-selected to include those that target an important mediator of cell health and toxicity, the peroxisome proliferator activated receptor gamma (PPARγ), in liver cells identified through query of the ToxCast/Tox21 database. These co-occurring chemicals were thus hypothesized to exert joint effects on PPARγ expression. To test this critical hypothesis, five commonly co-occurring chemicals, namely benzyl cinnamate, butyl paraben, decanoic acid, eugenol, and sodium dodecyl sulfate, were tested individually and in combination for cytotoxicity and PPARγ gene expression in human liver HepG2 cells. Findings support the potential joint action of these chemicals on PPARγ expression, highlighting mixtures-induced changes that were increased in comparison to individual chemical-induced changes, even when tested at lower respective doses in mixture form. Together, this study demonstrates the utility of in silico-based methods to identify chemicals that co-occur in the environment for mixtures toxicity testing, and highlights relationships between understudied chemicals and changes in PPARγ-associated signaling.Bachelor of Science in Public Healt