Individual and combined mechanistic toxicity of sulfonamides and their implications for ecological risk assessment in the Three Gorges Reservoir Area (TGRA), China.

Sulfonamides (SAs) are conventional veterinary antibiotics that pose ecological risks in the aquatic environment. This study aims to evaluate the environmental concerns of SAs in the Three Gorges Reservoir Area (TGRA) and their toxicogenetic implications. Here, we employed various in vitro and in vivo bioassays to determine the combine toxicogenetic effects of SAs, which were further confirmed through applying Combination Index (CI) and Independent Action (IA) models. Among the investigated SAs, sulfamethoxazole (SMX) appeared as the individual chemical with relatively high environmental effects and elevated in vitro and in vivo toxicity. Importantly, exposure to the binary mixtures of SAs induced higher developmental toxicity and significantly perturbed the detoxification pathway in zebrafish, compared to that of individual compound exposure. Moreover, the CI and IA models indicated greater synergistic effects of SAs binary mixtures as SMX-SMR, SMX-ST, and SPY-ST on the Acinetobacter sp. Tox2 at Fa = 0.5. Contrarily, IA model predicted the additive, antagonistic and synergistic effects of SAs mixtures on the transcriptional responses of detoxification pathways in zebrafish, implying the different mode of actions (MoAs) for SAs to induce mixture toxicity in vivo. Thus, the nature of toxicological interactions of SAs should be considered while performing their ecological risk assessment.