Plastic additives comprise many substances that serve numerous purposes in the plastic industry, such as assisting in the moulding of plastics and improving optimal performance. One of the bisphenols, namely, bisphenol A (BPA), is a widely used additive in the plastic industry and is now restricted by the European Union due to its proved toxicity. This additive is being replaced by analogues such as bisphenol E (BPE) and bisphenol Z (BPZ). However, there is a need to better understand their potential toxic effects to validate if they constitute safer alternatives. Thus, this study aimed at making a comparative assessment of the cytotoxicity of BPA, BPE, and BPZ to amphibian cell lines (A6 and XTC-2 - cell lines of Xenopus laevis), as Amphibia is the class of vertebrates with the highest proportion of species threatened with extinction. The cell lines were exposed for 24 h, 48 h, and 72 h to eight concentrations of each bisphenol and cell viability was assessed through each time point. Overall, the median lethal concentrations (LC₅₀) revealed that A6 cells are more sensitive to these chemicals than XTC-2. The obtained data support the premise that BPE and BPZ are less toxic to amphibian cell lines than BPA. Thus, based on the 72h LC₅₀, the cytotoxicity can be ranked as BPA>BPZ>BPE (45.48 mg/L, 57.1 mg/L, and 64.7 mg/L, respectively) for XTC-2 cells. A similar trend was observed for A6 cells (24.6 mg/L, 32.1 mg/L, and 41.6 mg/L for BPA, BPZ, and BPE, respectively). Thus, the data support that these BPA alternatives appear less toxic, but more studies must be performed and other endpoints assessed to fully understand their highest environmental safety.