3-Substituted 2-halopropenals: mutagenicity, detoxification and formation from 3-substituted 2,3-dihalopropanal promutagens.
The mutagenicity of halopropenals for Salmonella typhimurium strain TA100 is as follows (revertants/nmole): 2-halopropenals [H2C = C(X)CHO], F = less than 0.6, Cl = 135, Br = 1140 and I = less than 2.4; 3-substituted-2-halopropenals [CH3CH = C(X)CHO], Cl = 68 and Br = 108; [C6H5CH = C(X)CHO], Cl = less than 1 and Br = 5; [ClCH = C(Cl)CHO], 91; [CH3(CH2)2CH = C(Br)CHO], less than 1; [(CH3)2C = C(Br)CHO], less than 0.5. Each of the active compounds is detoxified by the liver S9 fraction. Glutathione also detoxifies the 2-halopropenals and 2-halobutenals, more rapidly for the bromo than the chloro analogs. The mutagenic potency on metabolic activation of the herbicide diallate by microsomes or the S9 fraction is attributable to approximately 50% conversion to 2-chloropropenal when corrected for detoxification in these systems or with GSH. There is no correlation between mutagenicity and reactivity with the model thiol, 4-nitrobenzenethiol. The mutagenicity of 2,3-dichloro- and 2,3-dibromo-propanals and the corresponding dihalobutanals is accounted for by their rapid dehydrohalogenation to the corresponding 2-haloalkenals under physiological conditions. Chemicals that are metabolized to 2,3-dichloropropanal, 2,3-dichlorobutanal, their dibromo analogs, or to the corresponding 2-halopropenals and 2-halobutenals should therefore be considered as candidate promutagens.
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology; D006219:Halogens / Q000378:metabolism / Q000494:pharmacology; D006540:Herbicides / Q000378:metabolism* / Q000494:pharmacology; D008658:Inactivation, Metabolic; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D000447:Aldehydes; D006219:Halogens; D006540:Herbicides; D009153:Mutagens; D013438:Sulfhydryl Compounds; C014712:4-nitrothiophenolate; D005978:Glutathione