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GENOTOXICITY STUDIES OF DRINKING WATER MIXTURES
Impact/Purpose:
In vitro assays are used to evaluate the relative mutagenicity of complex mixtures of DBPs in concentrated extracts of drinking water treated with different disinfectants. Based on these and other screening studies, additional longer-term in vitro studies can be conducted which can assist in evaluating the relative toxicity and carcinogenicity of simple or complex mixtures. This may be important for designating which primary and secondary disinfectants(s) are recommended to be used in the Stage 2 rule and what risk assessment approaches best describe the risk for cancer when exposed to multiple chemicals.
Description:
Investigations into the mutagenicity and mutational mechanisms of single chemicals within drinking water as well as of organic extracts of drinking water are being pursued using the Salmonella (Ames) mutagenicity assay as well as in human samples. For example, the semi-volatile compound dichloroacetic acid (DCA) has been shown to be mutagenic, inducing C to T base substitutions in Salmonella. We have shown that the trihalomethanes other than chloroform are activated to a mutagen by GST-theta in a transgenic strain of Salmonella. These studies have been extended to humans, who are polymorphic for GST-theta, and research is ongoing in this area. In addition, a recently detected class of disinfenction by-product, the halonitromethanes, have been evaluated in Salmonella and shown to be 10X more mutagenic than the regulated halomethanes. Because drinking water is a complex mixture, we have collaborated with ORD/NRMRL to obtain organic extracts of drinking water disinfected by various methods, such as chlorination, chloramination, ozonation, etc. These extracts have then been evaluated in Salmonella for mutagenicity, and the mutants have been analyzed at the molecular level to ascertain what mutations were induced by the mixtures. These studies have shown that chlorinated drinking water is more mutagenic than chloraminated or ozonated drinking water and that most of the mutations induced by these organic extracts are C to A base substitutions. This mutation spectrum is different from that induced by the haloacids or halomethanes and reflects the fact that neither the haloacids nor halomethanes, which are semi-volatile compounds, are present in the organic extracts of drinking water, which contain the nonvolatile components. The mutation spectra of these organic extracts are most similar to that of MX, the chlorinated furanone that accounts for much of the mutagenic activity drinking water. Current efforts are focusing on nanoparticles, MX, and other disinfection byproducts for their ability to induce germ cell mutations in mice.