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A novel approach to triazole fungicides risk characterization: Bridging human biomonitoring and computational toxicology.
Marciano, Luiz P A; Kleinstreuer, Nicole; Chang, Xiaoqing; Costa, Luiz F; Silvério, Alessandra C P; Martins, Isarita.
Afiliación
  • Marciano LPA; Laboratory of Toxicant and Drug Analyses, Department of clinical and toxicological analysis, Federal University of Alfenas - Unifal-MG, Alfenas, Minas Gerais, Brazil.
  • Kleinstreuer N; National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
  • Chang X; Inotiv-RTP, Morrisville, NC, USA.
  • Costa LF; Laboratory of Toxicant and Drug Analyses, Department of clinical and toxicological analysis, Federal University of Alfenas - Unifal-MG, Alfenas, Minas Gerais, Brazil.
  • Silvério ACP; University José do Rosário Vellano - UNIFENAS, Alfenas, Minas Gerais, Brazil.
  • Martins I; Laboratory of Toxicant and Drug Analyses, Department of clinical and toxicological analysis, Federal University of Alfenas - Unifal-MG, Alfenas, Minas Gerais, Brazil. Electronic address: isarita.sakakibara@unifal-mg.edu.br.
Sci Total Environ ; 953: 176003, 2024 Sep 03.
Article en En | MEDLINE | ID: mdl-39236816
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Total Environ Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Total Environ Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos