Azole antifungals in food and environmental matrices: occurrence and comparative assessment with predicted no effect...

Azole antifungals are widely used to treat fungal infections in humans, animals, and plants, and as fungicides to protect crops and post-harvest commodities. Their extensive use favors environmental dissemination, with residues frequently detected in surface waters, wastewater effluents, soils, and food-related matrices. Given that many fungal infections originate from environmental sources, the presence of antifungals in these settings may contribute to the selection and spread of antifungal resistance, representing a growing One Health concern. This systematic review aimed to evaluate the occurrence of azole antifungals in environmental and food-related matrices and to assess their potential ecological, public -health, and food-system risks by comparing reported concentrations with available Predicted No Effect Concentration (PNEC) values. The systematic literature review was conducted in accordance with PRISMA guidelines, where studies reporting the detection of azole antifungals in surface water, food, wastewater effluents, and soil were included. A total of 83 studies met the inclusion criteria. Voriconazole, clotrimazole, ketoconazole, and fluconazole were among the most frequently detected medical azoles across surface water, wastewater effluents, food, and soil samples, while several agricultural azoles were also detected in matrices directly connected with crop production and aquatic food chains. Concentrations in surface waters often exceeded PNEC values, indicating potential risks to environmental quality, antifungal efficacy, and food-system sustainability, as and human health. In addition, conventional wastewater treatment processes reveal to be insufficient for the complete removal of these compounds, facilitating their persistence and reintroduction into the environment and, potentially, into agricultural systems through irrigation, sludge application, and aquatic trophic transfer. In conclusion, the widespread presence of azole antifungals in environmental matrices, including food products, together with their incomplete removal by conventional wastewater treatment processes, may contribute to the selection, emergence, and dissemination of antifungal resistance. These findings highlight the need for integrated surveillance across water, soil, wastewater, food products, and agricultural inputs, as well as more efficient treatment technologies, residue monitoring, integrated pest management, and responsible microbiome-based innovations to reduce antifungal contamination and associated food-sector risks.