Metabolic activation of 3-(2-chloroethoxy)-1,2-dichloropropene: a mutagen structurally related to diallate, triallate, and sulfallate.
3-(2-Chloroethoxy)-1,2-dichloropropene (CP), a Salmonella promutagen that was recently isolated from a sample of residue organics previously concentrated from drinking water, is structurally related to three other chlorinated promutagens, the S-chloroallyl thiocarbamate herbicides diallate, triallate, and sulfallate. These four chloroallyl ether compounds were found to be similar with respect to strain specificity, potency, and requirement for specific metabolic activation. The 9,000g supernatant (S9) fractions from polychlorinated biphenyl Aroclor 1254- or phenobarbital-induced rats metabolized the four chloroallyl ethers to mutagenic products, whereas S9 from 3-methylcholanthrene-induced or uninduced rats did not. The metabolic activation of CP, diallate, and triallate to mutagens was catalyzed by the 100,000g microsomal pellet of S9 alone, but the activation of sulfallate to mutagenic metabolites required both microsomal and cytosolic fractions of S9. Direct-acting (minus S9) mutagenic metabolites of diallate and triallate could be extracted into methylene chloride from S9 incubation mixtures. Incubations containing S9 and either sulfallate or CP did not yield methylene chloride-extractable metabolites with direct-acting mutagenic activity. On the basis of these results and those from previous studies on the metabolism of diallate, triallate, and sulfallate, a tentative model for the metabolic activation of CP is proposed in which this chloroallyl ether undergoes alpha-carbon hydroxylation to form multiple mutagenic products.
D000498:Allyl Compounds; D000818:Animals; D001711:Biotransformation; D002219:Carbamates; D003600:Cytosol / Q000378:metabolism; D006540:Herbicides / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D000498:Allyl Compounds; D002219:Carbamates; D006540:Herbicides; D006843:Hydrocarbons, Chlorinated; C040100:3-(2-chloroethoxy)-1,2-dichloropropene