Developmental neurotoxicity of bisphenol F and bisphenol S in animal model systems: A literature review

Neurodevelopmental disorders have complex etiologies, stemming both from genetic and environmental risk factors, including gestational exposure to bisphenol A (BPA). BPA is an endocrine-disrupting chemical widely used in the synthesis of plastics and epoxy-resins. In 2012, the Food and Drug Administration issued a ban on the use of BPA in certain baby and childhood products, which contributed to the proliferation of BPA-free products. To make products without BPA, plastic and epoxy manufacturers often use chemical analogs, including bisphenol F (BPF) and bisphenol S (BPS). However, the structural and biochemical similarities BPF and BPS share with BPA suggest they may have similar molecular and cellular impacts on the developing nervous system, despite consumers generally regarding BPA-free products as safer alternatives. In this review, we synthesized all available peer-reviewed primary literature to date reporting on the neurodevelopmental impacts of BPF and/or BPS in animal models. In total, 61 papers were identified as relevant to the topic, including evaluation of BPF- and BPSassociated neurodevelopmental phenotypes such as changes in neurodevelopmental gene expression, the proliferation and differentiation of neural stem cells, synaptogenesis, central nervous system morphology, neuronal cell death, and behavior. Though less extensively studied than BPA, the collective works described here indicate that BPF and BPS can act as developmental neurotoxicants in animal models, urging further mechanistic and epidemiological analyses of these bisphenol analogs, as well as a reconsideration by regulatory agencies of policies surrounding their usage.