Styrene metabolism, genotoxicity, and potential carcinogenicity.
This report reviews styrene biotransformation, including minor metabolic routes, and relates metabolism to the genotoxic effects and possible styrene-related carcinogenicity. Styrene is shown to require metabolic activation in order to become notably genotoxic and styrene 7,8-oxide is shown to contribute quantitatively by far the most (in humans more than 95%) to the genotoxicity of styrene, while minor ring oxidation products are also shown to contribute to local toxicities, especially in the respiratory system. Individual susceptibility depending on metabolism polymorphisms and individual DNA repair capacity as well as the dependence of the nonlinearity of the dose-response relationships in the species in question and the consequences for risk evaluation are analyzd.
Vodicka
Pavel
P
Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Koskinen
Mikko
M
Naccarati
Alessio
A
Oesch-Bartlomowicz
Barbara
B
Vodickova
Ludmila
L
Hemminki
Kari
K
Oesch
Franz
F
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D004247:DNA / Q000187:drug effects / Q000235:genetics; D018736:DNA Adducts / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D009153:Mutagens; D013343:Styrenes / Q000378:metabolism* / Q000633:toxicity*
D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D013343:Styrenes; D004247:DNA