Metabolomic evaluation of rat liver and testis to characterize the toxicity of triazole fungicides

The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (H-1-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for 14 days with myclobutanil or triadimefon, at two dose levels for each triazole. Following exposure, serum, liver, and testis were collected and processed for NMR analysis. principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) of the resulting spectra were used to determine changes in metabolite profiles as a result of exposure. Using this approach, responses common to both triazoles were identified, as well as responses indicative of differences in the toxicity of these two compounds. Although changes were observed in serum metabolites following exposure, none were robust enough to be considered a biomarker of exposure/effect. A number of metabolic changes were, however, observed in the liver with both triazoles, particularly, in metabolites related to the methionine cycle. The testes of myclobutanil-exposed animals displayed altered levels of creatine and creatinine, consistent with testicular toxicity. Overall, the results of this study Support the possible application of a metabolomics approach to assessing the toxicity of triazole fungicides and identifying biomarkers of exposure and/or effect.