Mutagenicity of hexachlorobutadiene, perchlorobutenoic acid and perchlorobutenoic acid chloride.
Hexachloro(1,3)butadiene (HCBD) is a well known environmental contaminant. The nephrocarcinogenic potential of HCBD has been shown in long-term studies with rats. Experiments were performed to assist in determining whether this effect is mediated by epigenetic or genotoxic mechanisms and to compare the mutagenic properties of HCBD with those of its monooxidation products, perchloro-3-butenoic acid (PCBA) and perchloro-3-butenoic acid chloride (PCBAC), which are conceivable metabolites of HCBD. All 3 compounds are mutagenic to the Salmonella typhimurium tester strain TA100. The mutagenic effect is dose-dependent and parallels the chemical reactivity of the compounds. HCBD is only mutagenic in the presence of drug-metabolizing enzymes (S9 mix) with an increased protein content. The mutagenic response after incubation with PCBAC and PCBA is 2-3-fold that of HCBD. Additionally, both PCBAC and PCBA exert a mutagenic response in the absence of S9 mix. The experiments support the assumption of a genotoxic potential of HCBD.
D000818:Animals; D001711:Biotransformation; D002070:Butadienes / Q000633:toxicity*; D005659:Fungicides, Industrial / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D002070:Butadienes; D005659:Fungicides, Industrial; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; C042167:pentachloro-3-butenoic acid chloride; C042110:2,2,3,4,4-pentachloro-3-butenoic acid; C001335:hexachlorobutadiene