Plastic additives differentially affect the transcriptome of MCF-7 breast cancer cells

Bisphenol K (BPK) was the most potent chemical tested, activating ERα at the lowest concentrations, followed by plastic additive 08 (PA08), and bisphenol A (BPA). Despite similar potencies, transcriptomic biomarkers revealed mechanistic differences: plastic additives that shared similar chemical features as BPA activated the ERα, whereas several others with different functional groups inhibited the biomarker. Pathway and upstream regulator analyses further showed that BPA-like plastic additives perturbed ERα–related pathways, while other plastic additives enriched fewer and often of opposing directionality gene sets.

At the highest concentrations tested, many plastic additives also activated stress biomarkers and inhibited proliferation. These findings suggest that while many plastic additives display broadly similar in vitro potencies, they diverge in ERα regulation and downstream pathways. This study demonstrates the reproducibility and utility of HTTr for chemical screening, supports grouping of ERα-active plastic additives for read-across, and highlights the need for further screening of plastic additives.