Dichloroacetic acid and related compounds: induction of prophage in E. coli and mutagenicity and mutation spectra in Salmonella TA100.
We performed three types of studies to evaluate the genotoxicity of the chlorinated organic solvent perchloroethylene (PERC or tetrachloroethylene) and its volatile metabolites, trichloroacetyl chloride (TCAC) and trichloroacetic acid (TCA), as well as the volatile metabolites of trichloroethylene, i.e. dichloroacetyl chloride (DCAC), dichloroacetic acid (DCA), and 2,2,2-trichloroethanol (TCE). In the first set of studies, which involved the evaluation of these chemicals in the Microscreen prophage-induction assay, only DCA (+S9) was genotoxic, producing 6.6-7.2 plaque-forming units/mM. This places DCA among the weakest of the > 100 chemicals that have been identified previously as inducers of prophage in this assay. In the second set of studies, which involved the evaluation of these chemicals in the vapor state in Salmonella TA100 using a Tedlar bag vaporization technique, DCA (+/-S9), DCAC (-S9), and TCAC (+/-S9) were mutagenic, producing 3-5x increases in revertants/plate relative to the background. S9 enhanced the mutagenic potency of DCA but had no effect on the mutagenic potency of TCAC. The potencies ranged from 0.7 to 3.9 rev/p.p.m., resulting in a potency ranking of DCA > DCAC approximately TCAC. The lowest effective concentrations were 50-300 p.p.m., which are similar to those for ethylene oxide and epichlorohydrin in this assay. In the third set of studies, the mutation spectra of DCA, DCAC, and TCAC were determined at the base-substitution allele hisG46 of Salmonella TA100. DCA and DCAC induced primarily G.C-->A.T transitions, whereas TCAC induced primarily G.C-->T.A transversions, which was also the predominant mutation among the background revertants.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC 27711.
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DeMarini
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Perry
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Shelton
D001483:Base Sequence; D062845:Chloroacetates; D003090:Coliphages / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000821:virology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009154:Mutation; D016133:Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013750:Tetrachloroethylene / Q000494:pharmacology; D014241:Trichloroethylene / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*
D062845:Chloroacetates; D017931:DNA Primers; D004269:DNA, Bacterial; D014241:Trichloroethylene; D003999:Dichloroacetic Acid; D013750:Tetrachloroethylene