Inhalation toxicity studies were designed to study the toxicity and potential carcinogenicity of styrene, alpha-methylstyrene, and divinylbenzene. Styrene was the first chemical in this series of related compounds to be studied. Styrene toxicity and metabolism have been studied extensively in rats; however, data for a second species is needed by regulatory agencies for risk assessment and setting standards. A series of experiments was conducted to characterize the toxicity of styrene in mice. Male B6C3F1 mice were considerably more susceptible than females to the lethal effects of styrene. Both sexes demonstrated a non-linear dose response where hepatotoxicity and mortality were greater at 250 ppm than at 500 ppm, even though the blood levels of styrene oxide, the presumed toxic metabolite, were higher at 500 ppm. In a study comparing susceptibility of different mouse strains to styrene toxicity, mortality was greatest in B6C3F1 mice, intermediate in Swiss mice, and lowest in DBA/2 mice. Although no DBA/2 mice died during styrene exposure, the incidence and severity of hepatotoxicity was similar in DBA/2 and B6C3F1 mice. Blood levels of styrene oxide were highest in B6C3F1 mice, intermediate in DBA/2 and lowest in Swiss mice. These data will be used to select the appropriate mouse strain and dose levels for two-year chronic toxicity and carcinogenicity studies of styrene in mice.
