Effects of Tetramethyl Bisphenol F Exposure on Daphnia magna Growth, Reproduction, Locomotor Behavior and Transcriptomic Responses

Abstract

Environmental concerns have intensified due to the widespread use of bisphenol analogues as BPA alternatives. In this study, we assessed the toxicity of Tetramethyl Bisphenol F (TMBPF) on Daphnia magna and investigated the underlying mechanisms, at multiple biological levels, encompassing transcriptomic pathway alterations, growth and reproductive impairment, and behavioral changes. The 48 h EC₅₀ was 1.30 mg/L, which is lower than that of BPA, BPF, BPS, and BPAF. The 21 d NOEC for reproduction was 0.20 mg/L, classifying TMBPF as a GHS Category 2 chronic aquatic toxicant. Transcriptomic analysis revealed concentration-dependent mechanisms: at 0.2 mg/L, pathways related to carbohydrate metabolism and lysosomal function were enriched; at 0.4 mg/L, extensive transcriptional disruption affected RNA polymerase, neuroactive ligand–receptor interaction, xenobiotic metabolism, oxidative stress, and inflammatory pathways. These molecular changes corresponded with impaired growth, reproduction, and swimming behavior. Overall, this study provides integrative evidence that TMBPF exhibits pronounced acute and chronic toxicity to aquatic invertebrates and may pose a higher ecological risk than conventional bisphenols. The findings highlight the necessity for cautious evaluation and regulatory consideration of emerging bisphenol substitutes before their widespread environmental application.