Oral repeated dose toxicity study of bisphenol F in rats

Bisphenol F (BPF), developed as a safer alternative chemical to bisphenol A (BPA), is increasingly used in epoxy resin, coating, adhesive, and plastic production. However, despite its growing use, recent research indicates that it may be unsafe, underscoring the need for comprehensive and systematic toxicological studies to better elucidate its potential toxicological effects. Thus, in this study, we investigated BPF repeated-dose toxicity in rats based on the Organization for Economic Cooperation and Development guidelines for the testing of chemicals. BPF was administered to Crl:CD(SD) SD rats by oral gavage at doses of 0, 83, 250, and 500 mg/kg for 4 weeks, with additional 2-week recovery groups included to assess the reversibility or persistence of any toxic effects. Repeated oral exposure induced histopathological toxicity, including duodenal/jejunal lymphangiectasis at doses ≥250 mg/kg and focal/multifocal liver fibrosis at the 500 mg/kg dose. These histopathological findings, considered to be adverse, were accompanied by consistent BPF-related changes in clinical signs, clinical chemistry, coagulation, and organ weights. Therefore, the no-observable adverse effect level was considered to be 83 mg/kg/day. These results provide valuable evidence for BPF human health risk assessment and highlight the need for further studies in light of its increasing use in consumer products.