Developmental toxicity assessments for TBBPA and its commonly used analogs with a human embryonic stem cell liver differentiation model

Tetrabromobisphenol A (TBBPA) is widely used in industrial production as a halogenated flame retardant (HFR). Its substitutes and derivatives are also commonly employed as HFRs. Consequently, they can be frequently detected in environmental and human samples. The potential developmental toxicity of TBBPA and its analogs, particularly to the human liver, is still controversial or not thoroughly assessed. Therefore, in this study, we focused on the early stages of human liver development to explore the toxic effects of those HFRs, by using a human embryonic stem cell liver differentiation model. We concluded that nanomolar treatments (1, 10, and 100 nM) of those pollutants may not exert significant interference to liver development and functions. However, at 5 μM doses, TBBPA and its analogs severely affected liver functions, such as glycogen storage, and caused lipid accumulation. Furthermore, TBBPA-bis(allyl ether) showed the most drastic effects among the six compounds tested. Taken together, our findings support the view that TBBPA can be used safely, provided its amounts are strictly controlled. Nonetheless, TBBPA alternatives or derivatives may exhibit stronger adverse effects than TBBPA itself, and may not be safer choices for manufacturing applications when utilized in a large and unrestricted way.