Biomonitoring and risk assessment of human exposure to triazole fungicides.

Risk assessment and biomarkers were evaluated in volunteers exposed to triazole fungicides in southern Minas Gerais, Brazil. Volunteers were divided into two groups: occupationally and environmentally exposed to pesticides (n = 140) and those unexposed (n = 50) from urban areas. Urine samples were analyzed by GC-MS for triazoles, and samples from men and women in the exposed group were quantified. Groups were further stratified by sex to evaluate the biomarkers results. Oxidative stress was indicated by biomarker analysis for occupationally exposed men with elevated malondialdehyde levels and reduced superoxide dismutase and catalase activity (p < 0.0001). Bile acid levels were also elevated in the exposed group (p < 0.0001). Biomarkers in this study suggest recent, reversible changes due to pesticide exposure. Liver enzyme levels showed no significant differences. The highest Estimated Daily Intake for epoxiconazole ranged from 0.534 to 6.31 µg/kg-bw/day for men and 0.657-8.77 µg/kg-bw/day for women in the exposed group. Considering the highest detected urinary triazole value, the calculated Hazard Quotient for epoxiconazole was 0.789 for men and 1.1 for women. Results indicate a health risk associated with environmental triazole exposure, highlighting the importance of biomonitoring in risk assessment to prevent intoxication and assist in mitigating adverse health effects from chronic pesticide exposure.

A novel approach to triazole fungicides risk characterization: Bridging human biomonitoring and computational toxicology.

Brazil stands as the world's leading coffee producer, where the extensive use of pesticides is economically critical yet poses health and environmental risks due to their non-selective mechanisms of action. Specifically, triazole fungicides are widely used in agriculture to manage fungal diseases and are known to disrupt mammalian CYP450 and liver microsomal enzymes. This research establishes a framework for risk characterization of human exposure to triazole fungicides by internal-dose biomonitoring, biochemical marker measurements, and integration of high-throughput screening (HTS) data via computational toxicology workflows from the Integrated Chemical Environment (ICE). Volunteers from the southern region of Minas Gerais, Brazil, were divided into two groups: farmworkers and spouses occupationally and environmentally exposed to pesticides from rural areas (n = 140) and individuals from the urban area to serve as a comparison group (n = 50). Three triazole fungicides, cyproconazole, epoxiconazole, and triadimenol, were detected in the urine samples of both men and women in the rural group. Androstenedione and testosterone hormones were significantly reduced in the farmworker group (Mann-Whitney test, p < 0.0001). The data show a significant inverse association of testosterone with cholesterol, LDL, VLDL, triglycerides, and glucose and a direct association with HDL (Spearman's correlation, p < 0.05). In the ICE workflow, active in vitro HTS assays were identified for the three measured triazoles and three other active ingredients from the pesticide formulations. The curated HTS data confirm bioactivities predominantly related to steroid hormone metabolism, cellular stress processes, and CYP450 enzymes impacted by fungicide exposure at occupationally and environmentally relevant concentrations based on the in vitro to in vivo extrapolation models. These results characterize the potentially significant human health risk, particularly from the high frequency and intensity of exposure to epoxiconazole. This study showcases the critical role of biomonitoring and utility of computational tools in evaluating pesticide exposure and minimizing the risk.

Assessment of cellular damage with cytome assay among environmental/occupational triazole.

The use of triazole fungicides is common in Minas Gerais, Brazil. However, the risk arising from excessive and often unprotected exposure can be harmful to farmers. Therefore, we evaluated volunteers, exposed to triazole fungicides for cellular damage caused by this pesticide. In the buccal micronucleus cytome assay (BMCyt), cells were analyzed. Urinary triazoles were analyzed by the Liquid-Liquid Extraction coupled with Gas-chromatography/mass-spectrometry (LLE-GC/MS). Statistical differences were found for all cell types evaluated in residents of rural areas (n = 145). Analysis of variance showed statistical difference in kariolytic and pyknotic cells, between the groups of men and women living in rural areas, with higher incidence in the male group. Likewise, higher concentrations triazoles in urine samples in the male group were observed. Greater cellular damage suggests increases in DNA damage, chromossomal instability and cell deaths. The results showed the urgency of the public management with the implementation of measures to minimize the pesticides exposure.