Predicted Endocrine Disrupting Activity of Unregulated Drinking Water Contaminants

During UCMR 1-4, nearly 10 million Americanswere exposedto pollutants that bound strongly to endocrine disrupting chemicals. Molecular docking has been used for the high-throughputscreeningof chemical interactions with target proteins in pharmaceutical andenvironmental applications. We determined the in silico binding affinity, protein-chemical interactions, toxic potential,and hormone equivalents of 96 organic Unregulated Contaminant MonitoringRule (UCMR 1-4) organic contaminants and agonist/antagoniststandards with 10 nuclear receptors associated with environmentalendocrine disruption. Endocrine-active pollutants and their toxicpotentials were mapped across United States Public Water Systems (PWS).The percent of inactive UCMR chemicals varied greatly, from & SIM;38%for the thyroid system (TR & alpha; and TR & beta;) up to & SIM;70%for the estrogen system (ER & alpha; and ER & beta;), due to the presenceof charged amino acid residues within the receptor's ligandbinding domains. Further, a majority of UCMR-detectable public watersystems (4,900/5,229) contained thyroid-active chemicals, includingperfluoroalkyl and polyfluoroalkyl substances (PFAS), haloacetic acids,and herbicide degradates. Most UCMR chemical classes were modeledwith low toxic potential in monitored PWSs serving populations thatvaried between a few thousand and 100 million people. Insecticides,pesticides, herbicides, hormones, and PFAS had moderate toxic potentialimpacting a population of 10,000-20 million people. The potentialfor endocrine disruption by unregulated chemicals in public watersystems calls for a further risk analysis of cumulative exposures.