title: Mutagenicity of chloroolefins in the Salmonella/mammalian microsome test. III. Metabolic activation of the allylic chloropropenes allyl chloride, 1,3-dichloropropene, 2,3-dichloro-1-propene, 1,2,3-trichloropropene, 1,1,2,3-tetrachloro-2-propene and hexachloropropene by S9 mix via two different metabolic pathways.
abstract: In the presence of S9 mix all allylic chloropropenes tested exert considerable indirect mutagenic activity which is most pronounced for 1,2,3-trichloropropene. Lower as well as higher chlorinated derivatives are clearly less mutagenic. Longer than standard incubation time (120 min instead of 20 min) at 37 degrees C always leads to an increase in mutagenic activity. An increase in concentration of rat-liver homogenate fraction (S9) in the metabolising system (S9 mix) enhances mutagenicity only for 1,3-dichloropropene, 2,3-dichloro-1-propene and for the cis isomer of 1,1,2,3-tetrachloro-2-propene. According to the effects of the enzyme inhibitors SKF525 1,1,1-trichloropropene-2,3-oxide and cyanamide the allylic chloropropenes fall into 3 groups distinguished by their mode of metabolic activation by S9 mix: (a) allyl chloride and 1,3-dichloropropene are hydrolysed to the corresponding allylic alcohols which can be oxidised to the respective acroleins (hydrolytic-oxidative pathway); (b) 2,3-dichloro-1-propene, 1,1,2,3-tetrachloro-2-propene and hexachloropropene are epoxidised in the C=C double bond, giving rise to reactive epoxides (epoxidative pathway); (c) only 1,2,3-trichloropropene is obviously activated by both these alternative metabolic pathways. Structural parameters like chloro-substitution of the central C atom of the C=C-C sequence and substituent-induced polarisation of the C=C double bond as well as cis/trans isomerism might be responsible for different substrate properties for the enzymes involved in allylic chloropropene metabolism, thus determining different degrees of activation by either one or both pathways.
mesh_terms: D000498:Allyl Compounds / Q000009:adverse effects*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003484:Cyanamide / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000009:adverse effects*; D008862:Microsomes, Liver / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014239:Trichloroepoxypropane / Q000494:pharmacology
chemical_list: D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D014239:Trichloroepoxypropane; C043065:2,3-dichloro-1-propene; C013281:1,1,2,3-tetrachloropropene; D003484:Cyanamide; C048540:hexachloropropene; C048539:1,2,3-trichloropropene; C023891:1,3-dichloro-1-propene; D011335:Proadifen; D005978:Glutathione; C023698:allyl chloride