Bisphenol A (BPA) is a chemical widely used in the production of plastics and resins, recognized as an endocrine disruptor. Due to its associations with disorders affecting the brain, heart, and reproductive system, the European Union banned its use in food-contact materials in December 2024, followed by Switzerland in July 2025.
Context and Study Objectives
In response to growing demand for “BPA-free” materials, the industry has substituted BPA with structural analogues such as bisphenol S (BPS) and bisphenol F (BPF). However, due to their structural similarity, concerns persist regarding the potential adverse effects of these substitutes.
A recent in vitro investigation, published in Environmental Science & Technology on August 16, 2025, evaluated BPA alongside 26 alternatives, offering critical perspectives on the safety of these compounds.
Key Findings
- Certain structural analogues—specifically bisphenol AF (BPAF) and bisphenol Z (BPZ)—activated the estrogen receptor α (ERα) with potency comparable to BPA .
- Other structurally modified compounds (with bulky substitutions) lost estrogenic activity but activated PPARγ, a different receptor, suggesting novel risk pathways.
- Additional observations included mitochondrial dysfunction and neurotoxicity linked to some BPA alternatives.
- 2,2,4,4-Tetramethyl-1,3-cyclopropanediols (TMCD) appeared promising, showing no specific activity in the conducted tests. Nonetheless, their distinct structure renders them unsuitable as direct BPA substitutes.
Regulatory Implications
The study's authors propose revising regulatory frameworks to treat BPA analogues with similar toxicological profiles as a unified group rather than individually. They recommend applying the methodologies developed in this study to other chemical classes for safer substitution and prioritization.
Conclusions
- “BPA-free” labels do not necessarily equate to safety—many substitutes may pose endocrine or toxicological risks similar to or different from BPA.
- Although TMCD shows promise, it is not functionally equivalent to BPA and requires further development.
- Regulatory frameworks should be revised to classify BPA analogues with similar toxicological profiles collectively.
- Rigorous testing protocols should be mandated before introduction of new compounds in the market.
Practical Recommendations
- In the short term, consumers can reduce exposure by using food storage containers made of glass, stainless steel, or other inert materials.
- Regulators are urged to extend precautionary measures to BPA analogues and adopt broader safety standards.
The industry must invest in developing materials with entirely different, non-toxicologically problematic structures.
Source ACS PUBLICATIONS.