The European Food Safety Authority (EFSA) has adopted guidance on the data requirements for the safety assessment of bisphenols other than bisphenol A (BPA, CAS 80-05-7) and their derivatives. The document was prepared by EFSA’s Panel on Food Contact Materials (FCM Panel) following a public consultation (FPF reported) and was published in the EFSA Journal on September 16, 2026.
The guidance was developed for Regulation (EU) 2024/3190, which prohibits the use of BPA in food contact materials (FCMs) and requires authorization of other hazardous bisphenols and bisphenol derivatives before they can be used in specific food-contact applications (FPF reported). Under the regulation, EFSA was tasked with specifying the scientific information needed to get authorization for the use of hazardous bisphenols in FCMs.
According to the guidance, “hazardous bisphenols” are substances classified under the Classification, Labelling and Packaging (CLP) Regulation (Regulation (EC) 1272/2008) as carcinogenic, mutagenic, toxic to reproduction (CMR), or endocrine disrupting for human health. EFSA states that the data requirements should also apply to bisphenols that are not currently classified as hazardous in order to help prevent regrettable substitutions. This represents a critical update from the draft guidance and addresses a concern raised by the Food Packaging Forum (FPF) during the public consultation on the draft guidance (FPF reported).
The guidance was informed by EFSA’s 2023 re-evaluation of BPA, which identified BPA as an immunotoxicant and reproductive toxicant at very low exposure levels, and also highlighted potential metabolic effects (FPF reported). EFSA notes that many bisphenol alternatives classified as hazardous may produce similar effects at comparable or lower doses.
Consequently, in the guidance EFSA proposes more extensive testing requirements for bisphenols than those typically requested for substances migrating into food at levels below 0.05 mg/kg food. For these low-exposure scenarios, applicants requesting authorization of alternative bisphenols are expected to provide data addressing immunotoxicity, developmental and reproductive toxicity, metabolic effects, and toxicokinetic behavior.
The guidance recommends conducting an extended one-generation reproductive toxicity (EOGRT) study based on OECD Test Guideline 443 to obtain information on immunotoxicity, developmental and reproductive toxicity (DART) and metabolic effects.
Where relevant data already exist, EFSA allows applicants to use a weight-of-evidence approach incorporating animal studies, non-animal methods, and other complementary approaches such as the read-across method. EFSA notes that in vitro and in silico methods can play an important role in evaluating immunotoxicity and other health effects, although their suitability must be scientifically justified.
EFSA also calls for three types of studies to address the toxicokinetic properties of hazardous bisphenols: an in vivo absorption, distribution, metabolism and excretion (ADME) study; an in vitro comparative metabolism (IVCM) study; and an in vitro intrinsic clearance (Clint) study.
The guidance further recommends that each in vitro toxicological study is complemented by an in vitro distribution study following OECD guidance. EFSA states that this is because “differences in uptake and metabolism between in vitro systems and humans can cause major differences… between in vitro and in vivo toxicity.”
For substances migrating between 0.05 and 5 mg/kg food, the same data requirements apply as for those migrating at levels below 0.05 mg/kg food. For migration levels above 5 mg/kg food, applicants must additionally provide long-term toxicity and carcinogenicity data in line with EFSA’s existing guidance for food contact chemicals.
References
EFSA Panel on Food Contact Materials et al. (September 16, 2026). “Guidance on the data requirements for the safety assessment of bisphenols other than Bisphenol A (BPA) and their derivatives.” EFSA Journal
EFSA Panel on Food Contact Materials, Enzymes and Processing Aids et al. (April 19, 2023). “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs.” EFSA Journal
EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food et al. (July 31, 2008). “Note for Guidance For the Preparation of an Application for the Safety Assessment of a Substance to be used in Plastic Food Contact Materials.” EFSA Journal
