| The disinfection of drinking water was perhaps the most important public health achievement of the 20th century. Drinking water disinfection by-products (DBPs) are an unintended consequence of a chemical reaction between natural and synthetic organic/inorganic materials in the source water and the particular disinfection method being utilized. Using calibrated microplate based mammalian cell assays we were able to utilize small quantities of synthesized DBP compounds and generate the world's largest quantitative, comparative, mammalian cell cytotoxicity and genotoxicity database. The particular focus of this dissertation was on nitrogen containing DBPs. Based on our previous results, bromoacetic acid, was utilized in a pioneering human toxicogenomic study. Normal, non-transformed human embryonic cells were used for this research and the cells were treated at a biologically relevant concentration of BAA that was at the lower limit of resolution of our genotoxicity assay. This toxicogenomic method, linked to a biological endpoint, defined bromoacetic acid as a non-threshold genotoxin and has led to the discovery that BAA-induced genotoxicity involves the generation of double strand DNA breaks. The work presented in this dissertation filled a large void in drinking water disinfection toxicity literature. This work serves as a foundation for future mechanistic toxicology of DBPs. |
