Comparative In Vitro Toxicity Assessment of Both Raw Water and Disinfected Drinking Water Using a Yeast Stress Response Multiplex Biomarker Assay and a Human Cell RT-qPCR Assay

Abstract:

Mixture toxicities of drinking water as results of a myriad of contaminants including disinfection byproducts (DBPs) and contaminants of emerging concern (CECs) are yet to be elucidated and crucial to public health. In vitro effect-based and omics-oriented toxicity evaluation approaches have shown rising potential for cost-effective and feasible monitoring of water risks. In this study, a recently established quantitative toxicogenomics-based yeast assay and a human cell RT-qPCR assay were employed for comparative toxicity evaluation of the organic extracts of 30 water samples collected from raw water and distribution systems at seven drinking water treatment plants in the United States. Twelve key proteins with high predictability for phenotypic endpoints of genotoxicity and oxidative stress, and five key genes previously shown to be indicative of DNA damage, oxidative stress, chemical stress and apoptosis were selected as molecular toxicity biomarkers in the yeast and human cell assays, respectively. Concentration-dependent toxicity fingerprints and distinct pathway-level perturbations were revealed among water samples from different geographical locations and treatment processes. Quantitative molecular toxicity endpoint Protein Effect Level Index (PELI) was derived, allowing for the comparison of toxicity profiles among samples and reference compounds. Increased toxicities in either or both DNA damage and oxidative stress were observed among four out of fifteen pairs of raw water/distribution system samples, indicating the potential toxicity induction due to the formation of DBPs and other transformation products during treatment processes that needs further investigation. This study reports an innovative biomarker-based approach for the evaluation of mixture toxicities of drinking water, which if in the future combined with chemical analysis, can be envisioned to identify the major toxicity drivers in drinking water and contribute to risk management.