Bisphenols are a group of chemicals used in polycarbonate plastics and epoxy resins, including in food contact applications (FPF reported). For a long time, bisphenol A (BPA, CAS 80-05-7) was the most widely used bisphenol, but it has become increasingly restricted. For example, it was banned in Europe in food contact applications due to its endocrine-disrupting properties (FPF reported and here). As awareness of BPA-related health concerns has grown, industry has replaced it with structurally similar alternatives. However, toxicity assessments have shown that these analogs are mostly just as hazardous (FPF reported and here), while toxicokinetic data are limited that describe their absorption, distribution, metabolism, and excretion (ADME).
To address this knowledge gap, Hélène Bigonne and co-authors from ETH Zürich, Switzerland, developed human physiologically based kinetic (PBK) models for BPA and size analogs. In an article published on September 25, 2025, in the journal Environmental Science & Technology, they reported that the assessed bisphenols differ significantly in their toxicokinetics. Upon oral exposure, internal concentrations varied by orders of magnitude between compounds, organs, and age groups.
For instance, bisphenol S (BPS, CAS 80-09-1) reached the highest levels in blood and testes, while bisphenol M (BPM, CAS 13595-25-0) accumulated most in the thyroid, and bisphenol AF (BPAF, CAS 1478-61-1) in breast tissue. Bisphenols also varied in their clearance rate. For example, “BPM concentration did not decrease during the 48 h following single dose exposure, did not reach the steady state in thyroid, testes, and breasts, and persisted beyond 96 h of simulation,” which affects its health concerns compared to other bisphenols with faster clearance rates.
Because BPA and its analogs differ markedly in toxicokinetics and internal exposure levels, the scientists recommend a chemical‑specific risk assessment. Given the large number of plastic chemicals (>16,000, FPF reported), such comprehensive exposure assessments are very time- and resource-intensive. For this reason, scientists call for switching from a risk- to a hazard-based approach to identify chemicals of concern, arguing that this is more efficient, simpler, and fit-for-purpose (FPF reported).
To predict the toxicokinetics of bisphenols, Bigonne and co-authors used a multimodel approach, integrating in vitro measurements of metabolism, computational prediction of gastrointestinal absorption, and rat-human extrapolation of enterohepatic circulation. They compared the model’s outcome with human experimental data of BPA and BPS where they found it to “generate reliable predictions” for BPA while those for BPS “were less accurate” than those from a previously developed model.
Reference
Bigonne, H. et al. (2025). “Human Internal Exposures of Bisphenol A and Six Data-Poor Analogs Predicted by Physiologically Based Kinetic Models with Multimodal Parametrization.” Environmental Science & Technology. DOI: 10.1021/acs.est.5c00513
