Long-term carcinogenicity bioassays on styrene administered by inhalation, ingestion and injection and styrene oxide administered by ingestion in Sprague-Dawley rats, and para-methylstyrene administered by ingestion in Sprague-Dawley rats and Swiss mice.

Styrene was administered to Sprague-Dawley rats by inhalation (300, 100, 50, 25, 10 and 0 ppm, 4 hours daily, 5 days weekly, for 52 weeks); by gavage (250, 50 and 0 mg/kg b.w. in olive oil, once daily, 4-5 days weekly, for 52 weeks), by intraperitoneal injection (50 and 0 mg in olive oil, four times at 2-month intervals), by subcutaneous injection (50 and 0 mg in olive oil, once). Styrene oxide was administered to Sprague-Dawley rats by gavage as styrene (250, 50 and 0 mg/kg b.w. in olive oil, once daily, 4-5 days weekly, for 52 weeks). The animals were kept under observation until spontaneous death. Para-methylstyrene was also administered by gavage to Sprague-Dawley rats at 500, 250, 50, 10 and 0 mg/kg b.w., and to Swiss mice at 250, 50, 10 and 0 mg/kg b.w., in olive oil, once daily, 5 days weekly, for 108 weeks and 78 weeks, respectively. The study was terminated when the survival rate reached 50% in at least one experimental group. Styrene, when given by inhalation, was found to cause an increase in total (benign and malignant) and malignant mammary tumors. Styrene oxide produced a high incidence of tumors in the forestomach (papillomas, acanthomas, and in situ and invasive squamous cell carcinomas). Para-methylstyrene was not shown to be carcinogenic.