Journal
TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS
Volume 22, Issue 2, Pages 113-128Publisher
WILEY-LISS
DOI: 10.1002/tcm.10010
Keywords
DBP; haloacetic acids; mutagenic potency; TA98; TA100; RSJ100; structure-function analysis
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We analyzed the cytotoxicity and mutagenicity of the drinking water disinfection by-products (DBPs) bromoform (BF), bromoacetic acid (BA), dibromoacetic acid (DBA), tribromoacetic acid (TCA), chloroform (CF), chloroacetic acid (CA), dichloroacetic acid (DCA), trichloroacetic acid (TCA), 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (NIX), and potassium bromate (KBrO3) in Salmonella typhimurium strains TA98, TA100, and RSJ100 +/- S9. Solvent controls of DMSO and ethanol and a positive control of ethylmethanesulfonate (EMS) were also analyzed. We developed a rapid microplate-based method to determine the cytotoxicity of the DBPs and we determined their mutagenic potencies. The distributions of the rank order for the cytotoxicity and mutagenicity of these DBPs were compared and the structure-function relationships were identified. TA100-S9 was the most sensitive strain for these DBPs. The rank order of the mutagenic potency adjusted with a cytoxicity factor was MX > BA > EMS > DBA > DCA > CA with TBA, TCA, BF, and CF not mutagenic. From a structure-function perspective, the brominated acetic acids were more cytotoxic and mutagenic than their chlorinated analogs. BA was 150x more mutagenic than CA. The mutagenic potency of the haloacetic acids was inversely related to the number of halogen atoms of the molecule. BA was 36x more mutagenic than DBA. The differential cytotoxicity expressed by the DBPs indicated that a cytotoxicity analysis enhanced the sensitivity of the mutagenicity data, which resulted in an enhanced.
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