Understanding how mixtures of co-used chemicals contribute to health risks remains a major challenge in consumer product safety assessment. This study evaluated the synergistic toxicity of triclosan (TCS) and co-occurring chemicals found in household cleaning products. We first calculated the margin of exposure (MoE) for TCS using representative cleaning-product use scenarios and point of departure (POD) values from regulatory reports. Most MoE values exceeded 100, indicating a low risk potential under conventional single-chemical assessment. We then conducted cytotoxicity testing for TCS and co-occurring chemicals in those products using four human cell lines (BEAS-2B, HepG2, Jurkat, and SH-SY5Y). Mixture modeling applied to concentration-response data sets yielded model deviation ratios (MDRs), quantifying departures from additivity. Eight mixtures showed MDR values ≥2, suggesting potential synergistic effects that would not be captured through single-chemical evaluations. Supporting mechanistic signals were identified through the integration of U.S. Environmental Protection Agency's ToxCast bioactivity data. Cross-referencing with the U.S. ChemExpo database further demonstrated that several synergistic combinations occur across multiple consumer product categories. Overall, this study illustrates that chemicals deemed low-risk under conventional assessment frameworks may exhibit previously undisclosed toxicity when used in mixtures, and it provides regulatory insights into the need to incorporate mixture effects into future consumer product risk assessment.
Jung et al. (Thu,) studied this question.