In Vitro Screening of 21 Bisphenol A Replacement Alternatives: Compared with Bisphenol A, the Majority of Alternatives Are More Cytotoxic and Dysregulate More Genes in Avian Hepatocytes.

An avian in vitro screening approach was used to determine the effects of 21 bisphenol A (BPA) alternatives. Cytotoxicity and dysregulation of genes associated with estrogen response and other toxicologically relevant pathways evoked by these alternatives were compared with BPA. Most of the BPA alternatives (15/21) were equally or more cytotoxic than BPA in chicken embryonic hepatocytes; variability in cell viability was associated with chemical structure and the log octanol-water partition coefficient (logP) values. A negative linear relationship (r  = 0.745; p = 0.49 ; n = 18) was observed between logP and the log median lethal concentration (logLC50) values. The least cytotoxic BPA alternatives elicited the greatest gene dysregulation and, overall, most of the alternatives altered more genes than BPA (measured with a custom polymerase chain reaction array). This overall approach shows promise for use as a screen for hazard-based prioritization of BPA replacement alternatives and to ideally identify those that may be less harmful and/or require additional toxicity testing. Environ Toxicol Chem 2021;40:2026-2033. © 2021 Her Majesty the Queen in Right of Canada Environmental Toxicology and Chemistry © 2021 SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.