DNA damage induced by fungicides triadimefon, triadimenol, and their mixture in human lymphocytes: cytogenotoxicity and computational analysis of metabolic pathways

Triadimefon (TF) and triadimenol (TN) are triazole fungicides widely used to prevent fungal infections in cereals, fruits, and other economically important crops. Their harmful effects on non-target organisms have been reported. This study investigated the cytogenotoxic effects of TF and TN, isolated and combined, at environmentally relevant concentrations (TF: 0.006, 0.012, and 0.024 mg/mL; TN: 1.5, 3.0, and 6.0 mg/mL; and 0.012 mg/mL TF + 3.0 mg/mL TN) on human lymphocytes using the trypan blue exclusion test and the comet assay. Additionally, <i>in silico</i> tools, BioTransformer and DIGEP-Pred, were employed to elucidate metabolic pathways more effectively for detoxifying these xenobiotics and to evaluate their putative effects on gene transcription, respectively. Exposure to TF and TN, either alone or in combination, did not affect lymphocyte viability at the tested concentrations. However, both compounds induced an increase in the percentage of DNA strand breaks after treatment. The <i>in silico</i> predictions suggested that the interaction with the cytochrome P450 isoforms (CYP1A2, CYP2A6, CYP2C9, and CYP2D6) differed for each compound analyzed. Gene expression prediction indicated that TF and TN may up-regulate genes involved with hormonal alterations, Alzheimer's disease risk, and cancer progression (SF1, SPON1, ADGRF5, and RORB). While they may down-regulate a gene involved with changes in heart rhythm and neurotoxicity (HCN1). In conclusion, our findings reinforced that the triazole fungicides TF and TN, while effective in agriculture, may pose risks to genomic stability in humans, highlighting the importance of biomonitoring studies in exposed populations.