Epidemiological investigations on the reproductive and developmental outcomes of rubber and plastic industry workers have focused on the potential developmental toxicity of styrene, an important occupational chemical, and its metabolite, styrene oxide. We have examined the developmental toxicity of styrene oxide using two in vitro culture systems: micromass cell cultures and whole embryo culture (WEC). Further, we have compared the effects of styrene oxide in both culture systems to the developmental toxicity of styrene in the micromass system. The ability of styrene oxide to affect the differentiation of rat embryo midbrain (CNS) and limb bud (LB) cells was compared to general cytotoxicity over 5 days in high-density micromass cultures. The IC50 for differentiation was 9.2 μgsol;ml (76 μM) for CNS and 6.7 μg/ml (56 μM) for LB. The LC50 for cytotoxicity was 9.6 μg/ml(80 μM) and 27.5 μg/ml(228 μM) for CNS and LB, respectively. The values for CNS sensitivities suggest that inhibition of differentiation is probably a consequence of high levels of cytotoxicity. In contrast, effects of styrene oxide on LB endpoints of differentiation were evident at concentration levels which had minimal effects on cell viability. Styrene alone or in the presence of an exogenous monooxygenase system had minimal effects when tested at concentrations 4-12 times the highest IC50 values seen with styrene oxide alone. In whole embryo culture experiments, styrene oxide produced growth retardation and embryo malformations (primarily neural) with an MC50 value of 20 μg/ml (167 μM). The LC50 value for styrene oxide was approximately 1.7-fold higher (33.2 μg/ml, 276 μM). Our in vitro studies suggest that further evaluations of the relationship of developmental toxicity and generalized cytotoxicity of styrene and its metabolite are needed, especially given the low concentrations at which effects were seen.
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