Use of Chemical Models and Structure-Activity Relationships to Identify Novel Disinfection By-Prod ucts of Potential Toxicological Concern

摘要

Chlorinated drinking water has been epidemiologically associated with increased risk of cancer, especially in the bladder, and adverse reproductive outcomes. A large number of chemicals have been identified as disinfection by-products (DBPs). Several by-product classes, such as the trihalo-methanes and haloacetic acids, have received substantial toxicological study. Although many of these have been found carcinogenic in animals, the combination of low potency as carcinogens and/or low concentrations in drinking water make them unlikely causes of the cancer risk of the magnitude suggested by epidemiology studies. To provide some direction for the resolution of this discrepancy, a strategy was developed to predict formation of novel by-products through reactions of chlorine with substructures found in natural organic matter (NOM). These potential disinfection by-products (DBPs) were examined using a quantitative structure toxicity relationship (QSTR) program, TOPKAT?, to identify those chemicals of sufficient toxicologic potency to account for epidemiologic findings, if present. A "weight of evidence" strategy was utilized to rectify the predictions of the multiple cancer models within TOPKAT? to identify those compounds that were most probably potent carcinogens. Potential