These studies evaluate the mode of action and human relevance of adverse effects seen in chronic animal studies. The findings conclude that it is unlikely uterine tumor effects would occur in humans given that current TBBPA exposure levels are approximately eight orders of magnitude (or more) lower than these doses that are associated with exceeding the capacity of key enzyme pathways in animal studies.1Source: Borghoff, S. J., D. Wikoff, S. Harvey, and L. Haws. “Dose-and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats.” Toxicology Reports 3 (2016) 190 – 201.,2Source: Wikoff, D. S., J. E. Rager, L. C. Haws, and S. J. Borghoff. “A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework.” Regulatory Toxicology and Pharmacology 77 (2016): 143-159.
Key Takeaways:
- Evidence demonstrates that the mode of action seen in the rats is only operative under repeated high-dose exposures.
- TBBPA-effects seen in the rat study are not feasible in humans when considering current exposure levels.
- Data provides further support that the proposed mode of action occurs under conditions of high-dose, chronic TBBPA administration to Wistar Han rats.
- It is unlikely that the effects observed in the NTP study would occur in humans given that current TBBPA exposure levels are approximately eight orders of magnitude lower than the doses that are associated with exceeding the capacity of conjugation pathways in animal studies.
