Azole fungicides and Aspergillus resistance, five EU agency report highlights the problem for the first time using a One Health approach

and Control, the European Chemicals Agency, the European Environment Agency, and the European Medicines Agency, with support of the European Commission's Joint Research Centre 1 .Resistance selection through azole fungicide exposure has been well documented in Aspergillus fumigatus, which is the primary cause of Aspergillus diseases in humans 2 .Certain triazole fungicides show activity against A. fumigatus, which is not a plant pathogen, but a saprophyte that is found in plant-and timber-waste piles 3 .Residues of azole plant protection products in the green-waste select for resistance, most dominantly due to two signature mutations in the Cyp51A target gene, known as TR 34 /L98H and TR 46 /Y121F/T289A 4 .These substitutions render medical azoles ineffective, contributing to excess mortality in patients who contract azoleresistant invasive aspergillosis 5 .The EFSA report is comprehensive and provides details on azole fungicides that have been authorized for use in European member states, examines evidence that supports a causative link between azole fungicide use and the development of azole-resistant Aspergillus disease, reviews drivers for environmental resistance selection, and proposes a risk assessment framework for current and new authorizations of azole fungicides.Approximately 10,000 tonnes of azole fungicides for plant protection are sold annually in the EU, accounting for >99% of azoles sold, with azole biocides, industrial azoles, and medical/veterinary azoles making up the remainder.The Netherlands and Germany rank as the top countries with respect to fungicide sales per hectare of arable land, but conclusions at a national level are inaccurate as use data were not available, and some member states refrained from providing data.Despite stable annual fungicide sales, accumulation of azoles in the environment is likely due to their long half-life in soils, posing unknown risks to human, animal, and ecosystem health 6 .To study environmental selection pressures, 12 fungicides were further assessed based on approval status and activity against Aspergillus.Risk assessment of environmental resistance selection was based on agricultural processes that produce waste streams that support the growth of A. fumigatus, and the presence of an azole selection factor, estimated by assessing the fungicide residue levels in relation to the predicted no effect concentrations for resistance (PNEC res ) derived from laboratory