Initial hazard assessment of 4-benzylphenol, a structural analog of bisphenol F: Genotoxicity tests in vitro and a 28-day repeated-dose toxicity study in rats

4-Benzylphenol (CAS No. 101-53-1), a structural analog of bisphenol F, has estrogenic activity in vitro and in vivo, as is the case with bisphenol F. 4-Benzylphenol is used in plastics and during organic synthesis. Since its safety is largely unknown, we conducted toxicity tests as part of screening risk assessment in an existing chemical safety survey program. Based on results of the Ames test and the chromosomal aberration test using Chinese hamster lung cells (OECD TG 471 and 473), 4-benzylphenol was determined to be non-genotoxic in vitro. In a 28-day repeated-dose toxicity study, Crl:CD (SD) rats were administrated 4-benzylphenol by gavage at 0, 30, 150, or 750 mg/kg/day (OECD TG 407). Consequently, body weight was lower in males at 750 mg/kg/day. In the liver, relative organ weights were increased in both sexes at 750 mg/kg/day, and centrilobular hepatocellular hypertrophy was observed in males at 150 and 750 mg/kg/day. In the forestomach, hyperkeratosis and hyperplasia of squamous cells were observed in males at 150 and 750 mg/kg/day, and in females at 750 mg/kg/day. Based on these results, we identified the NOAEL for 4-benzylphenol as 30 mg/kg/day, with a hazard assessment value (D-value) of 0.05 mg/kg/day corresponding to hazard class 3.