Review of styrene and styrene oxide long-term animal studies

Eleven long-term toxicity studies were reviewed on styrene and five on styrene oxide in an effort to evaluate the potential carcinogenic activity of these chemicals in animals. The styrene studies included inhalation exposure (rats, mice, guinea pigs, and rabbits), intragastric gavage (rats and mice), drinking water (rats), and intraperitoneal injection (rats), while styrene oxide exposure was via intragastric gavage (rats and mice) or skin painting (mice). Each study was reviewed and evaluated for details and adequacy of design, adequacy of reported data, and interpretation. The results of this review are 1. There was no convincing evidence of carcinogenic activity of styrene in animals, although many of the studies were considered inadequate. 2. Styrene oxide was carcinogenic to the forestomach of both sexes of rats and mice after gavage exposure and was associated with an increase in liver neoplasms in male mice in one study. No carcinogenic activity was observed in mice after dermal exposure (skin paint). 3. None of the studies of styrene or styrene oxide reported here are well suited for extrapolating potential carcinogenic activity of either compound to humans because all have deficiencies in design, conduct, interpretation, or utilized a less than ideal route of exposure. A chronic state-of-the-art inhalation study is needed to evaluate this aspect of hazard assessment.