A Systematic Review on the Toxicology of European Union-Approved Triazole Fungicides in Cell Lines and Mammalian Models

Triazole fungicides are widely used in agriculture but may pose risks to human health through occupational, accidental, or environmental exposure. This systematic review aimed to evaluate the toxicity of ten European Union-approved triazole fungicides in rodent models and cell lines. A total of 70 studies were included, reporting quantitative in vivo oral, dermal, or inhalation toxicity in mammals or quantitative in vitro cytotoxicity in human or mammalian cell lines; the exclusion criteria comprised publications not in English or not accessible. Literature searches were conducted in Web of Science, Google Scholar, and the Pesticide Properties DataBase (PPDB), and risk of bias in included studies was assessed using ToxRTool. Due to heterogeneity in study designs, reporting formats, and endpoints, data were synthesized descriptively. Quantitative endpoints included LD₅₀/LC₅₀ values for in vivo studies and LOEC, IC₅₀, LC₅₀, and EC₅₀ values for in vitro studies, while mechanistic endpoints highlighted apoptosis, oxidative stress, genotoxicity, and endoplasmic reticulum stress. Difenoconazole and tebuconazole were the most extensively studied compounds, whereas several triazoles had limited data. The limitations included heterogeneity of data and incomplete reporting, which restrict cross-study comparisons. Overall, the findings provide a comprehensive overview of potential human health hazards associated with EU-approved triazole fungicides and highlight critical knowledge gaps. The review was registered in Open Science Framework.