A health conundrum of bisphenol A and its alternatives: charting a path beyond the structural analogue substitution pitfall

With the restriction of bisphenol A (BPA) in certain consumer products due to its endocrine-disrupting properties, structurally analogous alternatives such as bisphenol S (BPS) and bisphenol F (BPF) have rapidly entered the market. This shift has led to a wave of “regrettable substitutions” - chemicals that appear more environmentally friendly but may pose comparable or even unforeseen risks. Based on the latest toxicological evidence and population biomonitoring data, this perspective highlights that most mainstream BPA alternatives exhibit estrogenic/anti-androgenic activity, metabolic disruption potential, reproductive toxicity, and neurodevelopmental effects similar to those of BPA. Their widespread presence, environmental persistence, and hidden health hazards expose critical weaknesses in the current “like-for-like substitution” regulatory approach. To address this challenge, it is imperative to establish a safer assessment framework that integrates early endocrine disruption screening with exposome-based evaluation. Shifting from “hazard substitution” to a “functional safe-by-design” strategy is critical to circumvent the pitfalls of structural-analogue substitution, protect public health, and support sustainable development.