Comparative screening of private, public, and bottled drinking water in vitro bioactivity

This study compares in vitro bioactivity profiles of extracts from private tapwater (51 samples), public tapwater (143 samples), and bottled water (31 samples), using high-throughput, multiplex, transcription factor screening. Of 48 biological end points tested, 25 showed significant (≥50% above the field blank) activity. Frequently detected (≥10% of samples) bioactivities (in decreasing order) included xenobiotic metabolism (pregnane X receptor [PXR], aryl hydrocarbon receptor [AhR]), antioxidant response (antioxidant response element-binding nuclear factor erythroid 2-related factor 2 [NRF2], activator protein 1 [AP-1]), endocrine signaling (estrogen receptor [ER], peroxisome proliferator-activated receptor [PPAR]), and metals response (metals response element [MRE]). Significant bioactivities were observed across all drinking water supplies, with some statistical differences identified. Bioactivities were moderately to strongly correlated with several individual exposure and corresponding benchmark- or activity-weighted metrics, particularly for disinfection byproducts. Significant (α = 0.05) but weak correlations between measured bioactivity resemblance patterns and those of the inorganic–organic exposure, toxicity-quotient (TQ), and exposure-activity-ratio (EAR) resemblance matrices suggest that key drivers of observed drinking water bioactivity were not captured by the extensive, targeted exposure assessment. Results highlight the need for effects-based monitoring combined with improved exposure analysis to better assess health risks from low-level contaminant mixtures in drinking water.