Predicted endocrine disrupting activity of unregulated drinking water contaminants

Authors: NGUYEN, THUY - Arizona State University; NSIAH, GLORIA APPIAH - Arizona State University; CROWDER, EMILY - Arizona State University; GARLAND, SARAH - Arizona State University; Williams, Clinton; CONROY-BEN, OTAKUYE - Arizona State University

Submitted to: ACS Environmental Science & Technology Water
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2023
Publication Date: 3/8/2024
Citation: Nguyen, Thuy, Nsiah, Gloria Appiah, Crowder, Emily, Garland, Sarah, Williams, C.F., Conroy-Ben, Otakuye 2024. Predicted endocrine disrupting activity of unregulated drinking water contaminants. ACS Environmental Science & Technology Water. 4(3): 1000-1013. https://doi.org/10.1021/acsestwater.3c00156.
DOI: https://doi.org/10.1021/acsestwater.3c00156

Interpretive Summary: Molecular docking is a computational tool used to predict the three-dimensional structure of large molecular weight complexes and estimate the strength of their binding interaction. Molecular docking simulations can provide valuable insights into the potential endocrine-disrupting activity of unregulated contaminants in drinking water. Using a molecular docking program called VirtualToxLab, researchers with Arizona State University and USDA-ARS in Maricopa, AZ, modeled the binding affinities of 96 organic contaminants, identified through the Unregulated Contaminant Monitoring Rule (UCMR), to 10 nuclear receptors involved in hormone regulation. The study revealed that over half of the tested contaminants showed some level of binding to these receptors, indicating potential endocrine-disrupting activity. Specifically, hormones, pesticides, herbicides, PFAS, and haloacetic acids were identified as having moderate to high potential for endocrine disruption, with varying levels of prevalence in public water systems. These results can be used by regulatory agencies, water treatment facilities, and public health authorities to better understand potential public health risks associated with endocrine-disrupting contaminants in drinking water.

Technical Abstract: Molecular docking has been used for the high-throughput screening of chemical interactions with target proteins in pharmaceutical and environmental applications. We determined the in silico binding affinity, protein-chemical interactions, toxic potential, and hormone equivalents of 96 organic Unregulated Contaminant Monitoring Rule (UCMR 1-4) organic contami-nants and agonist/antagonist standards with 10 nuclear receptors associated with environmental endocrine disruption. Endocrine-active pollutants and their toxic potentials were mapped across United States Public Water Systems (PWS). The percent of inactive UCMR chemicals varied greatly, from ~38% for the thyroid system (TRa and TRß) up to ~70% for the estrogen system (ERa and ERß), due to the presence of charged amino acid residues within the receptor’s ligand binding domains. Further, a majority of UCMR-detectable public water systems (4,900/5,229) contained thyroid-active chemicals, including perfluoroalkyl and polyfluoroalkyl substances (PFAS), haloacetic acids, and herbicide degradates. Most UCMR chemical classes were modeled with low toxic potential in monitored PWSs serving populations that varied between a few thousand and 100 million people. Insecticides, pesticides, herbicides, hormones, and PFAS had moderate toxic potential impacting a population of 10,000-20 million people. The potential for endocrine disruption by unregulated chemicals in public water systems calls for a further risk analysis of cumulative exposures. KEYWORDS: molecular docking, Unregulated Contaminant Monitoring Rule, endocrine disruption, public water systems.