Perspectives on the genotoxic risk of styrene.
Styrene is a highly reactive monomer widely used in the plastics industry. The potential for styrene to produce genotoxic effects has been studied extensively in experimental systems. Styrene can induce sister chromatid exchanges (SCE) and chromosome aberrations (CA) in vitro under test conditions that enhance metabolism of styrene to styrene 7,8-oxide (SO)or reduce detoxification of 50 by epoxide hydrolase. The in vivo animal data indicate that styrene is not clastogenic at concentrations (doses) likely encountered by humans under ambient or occupational exposure conditions. DNA binding studies with styrene in rats and mice demonstrated no increased adducts in mice compared to rats or in mouse lung compared to liver. As a result, DNA adducts in the lungs are unlikely to be the sole explanation of the development of lung tumors in mice exposed to styrene for 2 yr. Some epidemiological studies reported that DNA and/or protein adducts and DNA strand breaks result from occupational exposure to styrene and/or 50. Results of some of these studies, how-ever, are difficult to interpret, given that the statistical significance of reported effects (SCE, CA, and micronucleus formation) was often near or at p values of .05; dose and/or temporal response relationships often were missing; confounding variables could not be excluded; and, concomitant exposures to other industrial chemicals that are potentially genotoxic may also have occurred. These studies suggest that styrene, through metabolism to SO, could be clastogenic in humans at workplace levels in excess of 125 mg/m3. However, results from controlled animal studies involving in vivo exposure to styrene alone do not show clastogenic effects at exposures of up to 1500 mg/m3/d. In any event, these studies show that there is an apparent threshold for styrene-mediated effects.
Nestmann
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ER
CANTOX Health Sciences International, Mississauga, Ontario, Canada. enestmann@cantox.com
Lynch
B S
BS
Ratpan
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F
D000818:Animals; D002869:Chromosome Aberrations / Q000139:chemically induced*; D018736:DNA Adducts / Q000032:analysis; D004784:Environmental Monitoring; D006801:Humans; D016273:Occupational Exposure; D012306:Risk; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D020058:Styrene / Q000378:metabolism / Q000633:toxicity*
D018736:DNA Adducts; D020058:Styrene