Mutagenicity of 2-methylpropene (isobutene) and its epoxide in a modified Salmonella assay for volatile compounds.
The mutagenic properties of 2-methylpropene (MP) and 2-methyl-1,2- epoxypropane (MEP) were investigated in the Salmonella assay. A simple exposure system, consisting of gastight tissue culture flasks, was used. This method has the advantage that the volatile test chemical is present during the entire incubation period and that several concentrations of the investigated compound can be tested on a single day. MP is not mutagenic in strains TA100, TA102 and TA1535, and in the latter strain not even in the presence of metabolizing S9 mix. MEP is mutagenic in all the strains tested, as demonstrated by a clear dose-response relationship. Strain TA1535 seems to be most sensitive to MEP compared with the other bacterial strains studied. For this strain, the mutagenic activity of MEP decreased significantly in the presence of S9 mix, compatible with the epoxide being inactivated by epoxide hydrolase and by glutathione S-transferase, as reported previously. From the present study it can be concluded that the parent compound MP is not mutagenic, but that its primary metabolite MEP is a mutagenic substance. However, very high concentrations are necessary to induce a mutagenic effect and the epoxide is efficiently detoxified by different liver enzymes.
Cornet
M
M
Department of Toxicology, Vrije Universiteit Brussel, Belgium.
Castelain
P
P
Vercruysse
A
A
Laib
R
R
Kirsch-Volders
M
M
Rogiers
V
V
D000475:Alkenes / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity*; D008110:Liver Extracts; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D014835:Volatilization
D000475:Alkenes; D004852:Epoxy Compounds; D008110:Liver Extracts; D009153:Mutagens; C071507:2-methyl-1,2-epoxypropane; C008176:isobutylene