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Background Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile–butadiene–styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO). SO is mutagenic in bacteria and mouse lymphoma assays. It is clastogenic in cultured mammalian cells. However, styrene and SO are not clastogenic/aneugenic in rodents, and no rodent in vivo gene mutation studies were identified. Methods To investigate the mutagenicity of orally administered styrene, we used the transgenic rodent gene mutation assay to perform an in vivo mutagenicity test (OECD TG488). The transgenic MutaMouse was given styrene orally at doses of 0 (corn oil; negative control), 75, 150, and 300 mg/kg/day for 28 days, and mutant frequencies (MFs) were determined using the lacZ assay in the liver and lung (five male mice/group). Results There were no significant differences in the MFs of the liver and lung up to 300 mg/kg/day (close to maximum tolerable dose (MTD)), when one animal with extremely high MFs that were attributed to an incidental clonal mutation was omitted. Positive and negative controls produced the expected results. Conclusions These findings show that styrene is not mutagenic in the liver and lung of MutaMouse under this experimental condition.

The Japanese government requires risk assessment of chemicals under the Chemical Substances Control Law (CSCL). Toxicity data for polyoxymethylene (paraformaldehyde; CAS No.: 30525-89-4) for human health are insufficient though the chemical needs a screening assessment under the CSCL. Thus, polyoxymethylene was selected by the Safety Examination of Existing Chemicals and Safety Programmes of the Ministry of Health, Labour and Welfare (MHLW) to assess repeated-dose and reproductive/developmental toxicity. A combined toxicity screening was conducted following the OECD TG422. Male and female rats were administered the test chemical once daily by gavage at doses of 0 (control), 20, 60, or 200 mg/kg bw from 14 days before mating for a total of 28 to 61 days. The 200 mg/ kg bw/day dose caused a significant decrease in food consumption. Histopathological examination found ulcers in the forestomach and glandular stomach, and erosion and inflammatory cell infiltration in the submucosa of the glandular stomach at the end of dosing in both sexes. Inflammatory cell infiltration in the submucosa of the glandular stomach was also observed in both sexes after the recovery period. No reproductive and developmental toxicity was observed even at the highest dose. A no-observed-adverse-effect level (NOAEL) for repeated-dose toxicity was 60 mg/kg bw/day, and a NOAEL for reproductive and developmental toxicity was 200 mg/kg bw/day, the highest dose tested.

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