RESUMEN
Emerging and persistent contaminants (EPC) pose a significant challenge to water quality monitoring efforts. Effect-based monitoring (EBM) techniques provide an efficient and systematic approach in water quality monitoring, but they tend to be resource intensive. In this study, we investigated the EPC distribution for various land uses using target analysis (TA) and non-target screening (NTS) and in vitro bioassays, both individually and integrated, in the upper Ping River Catchment, northern Thailand. Our findings of NTS showed that urban areas were the most contaminated of all land use types, although agriculture sites had high unexpected pollution levels. We evaluated the reliability of NTS data by comparing it to TA and observed varying inconsistencies likely due to matrix interferences and isobaric compound interferences. Integrating NTS with in vitro bioassays for a thorough analysis posed challenges, primary due to a scarcity of concentration data for key compounds, and potentially additive or non-additive effects of mixture samples that could not be accounted for. While EBM approaches place emphasis on toxic sites, this study demonstrated the importance of considering non-bioactive sites that contain toxic compounds with antagonistic effects that may go undetected by traditional monitoring approaches. The present work emphasizes the importance of improving NTS workflows and ensuring high-quality EBM analyses in future water quality monitoring programs.
RESUMEN
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.