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Analogy or fallacy, unsafe chemical alternatives: Mechanistic insights into energy metabolism dysfunction induced by Bisphenol analogs in HepG2 cells
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Researchers exposed human liver cells to three bisphenol A (BPA) replacements — chemicals used in plastics — and found that all three disrupted energy production in the cell's mitochondria (the cell's power generators), though through different mechanisms. The findings suggest that BPA substitutes are not necessarily safer and may cause their own form of metabolic harm.
Bisphenol analogs (BPs) are widely used as industrial alternatives for Bisphenol A (BPA). Their toxicity assessment in humans has mainly focused on estrogenic activity, while other toxicity effects and mechanisms resulting from BPs exposure remain unclear. In this study, we investigated the effects of three BPs (Bisphenol AF (BPAF), Bisphenol G (BPG) and Bisphenol PH (BPPH)) on metabolic pathways of HepG2 cells. Results from comprehensive cellular bioenergetics analysis and nontarget metabolomics indicated that the most important process affected by BPs exposure was energy metabolism, as evidenced by reduced mitochondrial function and enhanced glycolysis. Compared to the control group, BPG and BPPH exhibited a consistent pattern of metabolic dysregulation, while BPAF differed from both, such as an increased ATP: ADP ratio (1.29-fold, p < 0.05) observed in BPAF and significantly decreased ATP: ADP ratio for BPG (0.28-fold, p < 0.001) and BPPH (0.45-fold, p < 0.001). Bioassay endpoint analysis revealed BPG/BPPH induced alterations in mitochondrial membrane potential and overproductions of reactive oxygen species. Taken together these data suggested that BPG/BPPH induced oxidative stress and mitochondrial damage in cells results in energy metabolism dysregulation. By contrast, BPAF had no effect on mitochondrial health, but induced a proliferation promoting effect on cells, which might contribute to the energy metabolism dysfunction. Interestingly, BPPH induced the greatest mitochondrial damage among the three BPs but did not exhibit Estrogen receptor alpha (ERα) activating effects. This study characterized the distinct metabolic mechanisms underlying energy metabolism dysregulation induced by different BPs in target human cells, providing new insight into the evaluation of the emerging BPA substitutes.
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Researchers exposed clams to three common bisphenol A substitutes (BPAF, BPF, and BPS) at environmentally relevant concentrations to evaluate whether these replacement chemicals are truly safer. The study found that all three BPA analogues caused oxidative stress, cellular damage, and neurotoxic effects in clam tissues, suggesting that these widely used substitutes may pose similar ecological risks as the compound they were designed to replace.
Are the BPA analogues an alternative to classical BPA? Comparison between 2D and alternative 3D in vitro neuron model to assess cytotoxic and genotoxic effects
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Researchers compared the toxicity of BPA and five substitute chemicals (BPA analogues) that industry has been using as replacements, testing their effects on human nerve cells. Several BPA alternatives proved to be just as toxic or even more toxic than BPA itself, causing cell damage and genetic changes. This is concerning because these substitutes are found in plastics people use daily, and the findings suggest that replacing BPA with these analogues may not be making products safer for human health.
Single and multispecies microalgae toxicological tests assessing the impact of several BPA analogues used by industry
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Researchers tested five BPA chemical analogues (intended as safer BPA replacements) on three marine microalgae species, finding that several analogues — particularly BPFL and BPAF — were more toxic than BPA itself and that results from single-species tests did not reliably predict community-level outcomes, raising concerns about the safety of current BPA substitutes.
Bisphenol Analogs in Aquatic Environments and Their Effects on Marine Species—A Review
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This review summarized concentrations of bisphenol A analogs found across aquatic environments globally and assessed their toxic effects on marine species, finding that many BPA substitutes show similar endocrine-disrupting, oxidative, and genotoxic activity to the compound they replaced. The findings raise concerns that current BPA alternatives may not represent a meaningful safety improvement for aquatic ecosystems.
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Researchers investigated the toxicity of bisphenol A (BPA), its replacement bisphenol F (BPF), and their combination on primary producers, finding that both compounds harm eukaryotic green algae and raising concerns about the safety of BPA substitutes.
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