Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and chloral hydrate in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells.
The disinfection of water, required to make it safe for human consumption, leads to the presence of halogenated organic compounds. Three of these carcinogenic 'disinfection by-products', dichloroacetic acid (DCA), trichloroacetic acid (TCA) and chloral hydrate (CH) have been widely evaluated for their potential toxicity. The mechanism(s) by which they exert their activity and the steps in the etiology of the cancers that they induce are important pieces of information that are required to develop valid biologically-based quantitative models for risk assessment. Determining whether these chemicals induce tumors by genotoxic or nongenotoxic mechanisms (or a combination of both) is key to this evaluation. We evaluated these three chemicals for their potential to induce micronuclei and aberrations as well as mutations in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells. TCA was mutagenic (only with S9 activation) and is one of the least potent mutagens that we have evaluated. Likewise, CH was a very weak mutagen. DCA was weakly mutagenic, with a potency (no. of induced mutants/microgram of chemical) similar to (but less than) ethylmethanesulfonate (EMS), a classic mutagen. When our information is combined with that from other studies, it seems reasonable to postulate that mutational events are involved in the etiology of the observed mouse liver tumors induced by DCA at drinking water doses of 0.5 to 3.5 g/l, and perhaps chloral hydrate at a drinking water dose of 1 g/l. The weight-of-evidence for TCA suggest that it is less likely to be a mutagenic carcinogen. However, given the fact that DCA is a weak mutagen in the present and all of the published studies, it seems unlikely that it would be mutagenic (or possibly carcinogenic) at the levels seen in finished drinking water.
Harrington-Brock
K
K
Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709, USA.
Doerr
C L
CL
Moore
M M
MM
D000818:Animals; D002697:Chloral Hydrate / Q000633:toxicity*; D002869:Chromosome Aberrations; D003999:Dichloroacetic Acid / Q000633:toxicity*; D004202:Disinfectants / Q000633:toxicity*; D007940:Leukemia L5178 / Q000235:genetics*; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D013937:Thymidine Kinase / Q000235:genetics; D014238:Trichloroacetic Acid / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D018508:Water Purification
D004202:Disinfectants; D009153:Mutagens; D002697:Chloral Hydrate; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid; D013937:Thymidine Kinase