Triazole fungicides can manifest toxicity to a wide range of non-target organisms. Within this study we present a systematic review of the effects produced on the soil microbiota and activity of soil enzymes by the following triazole fungicides: cyproconazole, difenoconazole, epoxiconazole, flutriafol, hexaconazole, metconazole, myclobutanil, paclobutrazole, propiconazole, tebuconazole, tetraconazole, triadimenol, triadimefon, and triticonazole. Known effects of the triazole fungicides on the soil activity are dose dependent. High doses of triazole fungicides strongly affects the structure of the microbial communities in soil and usually decrease the soil microbial population and the activities of enzymes found in soil.

Difenoconazole is a chemical entity containing two chiral centers and having four stereoisomers: (2R,4R)-, (2R,4S)-, (2S,4R)- and (2S,4S)-difenoconazole, the marketed product containing a mixture of these isomers. Residues of difenoconazole have been identified in many agricultural products and drinking water. A computational approach has been used to evaluate the toxicological effects of the difenoconazole stereoisomers on humans. It integrates predictions of absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles, prediction of metabolism sites, and assessment of the interactions of the difenoconazole stereoisomers with human cytochromes, nuclear receptors and plasma proteins by molecular docking. Several toxicological effects have been identified for all the difenoconazole stereoisomers: high plasma protein binding, inhibition of cytochromes, possible hepatotoxicity, neurotoxicity, mutagenicity, skin sensitization potential, moderate potential to produce endocrine disrupting effects. There were small differences in the predicted probabilities of producing various biological effects between the distinct stereoisomers of difenoconazole. Furthermore, there were significant differences between the interacting energies of the difenoconazole stereoisomers with plasma proteins and human cytochromes, the spectra of the hydrogen bonds and aromatic donor–acceptor interactions being quite distinct. Some distinguishing results have been obtained for the (2S,4S)-difenoconazole: it registered the highest value for clearance, exposed reasonable probabilities to produce cardiotoxicity and carcinogenicity and negatively affected numerous nuclear receptors.

Herbicides are being used more and more to increase productivity in agriculture, but their excessive has been shown to lead to adverse effects on the environment, especially on the soil. Within this study the effect of the herbicide S-metolachlor on the activity of several enzymes (dehydrogenase, protease, phosphatase and urease) found in the loamy-clayey soil has been analyzed. There were seven experimental variants corresponding to the untreated soil and to the application of six distinct doses of S-metolachlor on soil samples maintained in laboratory conditions. Biochemical analyzes have been performed to assess the activities of the investigated enzymes at 7, 14 and 21 days, respectively, and several physiochemical parameters of the soil have been also monitored during these experiments. The data obtained in the experimental determinations were subjected to statistical analysis such as to evaluate if the changes in the activities of enzymes are significant and to establish if there are correlations between the evolution of analyzed enzymatic activities and the physicochemical parameters of the soil. Molecular docking approach has been also used to assess the interactions between the herbicide and investigated enzymes. The activities of studied enzymes decreased in a dose-dependent manner when the herbicide was applied. More than 21 days were necessary to recover the activities of dehydrogenase and protease in the soil treated with S-metolachlor, the activity of protease was recovered after 14 days and the activity of urease was recuperated after 7 days of incubation. This study also emphasized significant correlations between the enzymatic activities and some physicochemical parameters of the soil: pH, moisture, organic matter, nitrogen level and available phosphorus.

This study assesses the effects of the herbicide oxyfluorfen on the activities of enzymes and on the populations of soil microorganisms by considering experiments on soil samples maintained in both laboratory and in field conditions. Furthermore, the molecular docking approach was used to evaluate the interactions of oxyfluorfen with enzymes found in soil. There was a dose dependent inhibitory effect of oxyfluorfen against the activities of dehydrogenase, phosphatase, protease and urease. The enzymes activities obtained for the soil samples maintained under field conditions usually reflected a different trend than those obtained under laboratory conditions, emphasizing the influence of the soil physicochemical properties. For soil samples maintained in field conditions and for the normal dose of oxyfluorfen, dehydrogenase activity recovered after 14 days and a minimum of 21 days was necessary for the recovery of phosphatase, urease and protease activity, respectively. The most important parameters of soil influencing the activities of enzymes and the populations of microorganisms were the pH, N-NO₃ and N-NH₄ contents. A dose dependent behavior of populations of microorganisms found in soil treated with oxyfluorfen has been shown. There was a slight grows of the colonies of microorganisms when oxyfluorfen was applied, but this growth decreased with increasing the oxyfluorfen concentration.

Fungicides play an important role in crop protection, but they have also been shown to adversely affect non-target organisms, including those living in the aquatic environment. The aim of the present study is to combine experimental and computational approaches to evaluate the effects of flutriafol, metconazole, myclobutanil, tebuconazole, tetraconazole and triticonazole on aquatic model organisms and to obtain information on the effects of these fungicides on Lemna minor, a freshwater plant, at the molecular level. The EC₅₀ (the half-maximum effective concentration) values for the growth inhibition of Lemna minor in the presence of the investigated fungicides show that metconazole (EC₅₀ = 0.132 mg/L) and tetraconazole (EC₅₀ = 0.539 mg/L) are highly toxic, tebuconazole (EC₅₀ = 1.552 mg/L), flutriafol (EC₅₀ = 3.428 mg/L) and myclobutanil (EC₅₀ = 9.134 mg/L) are moderately toxic, and triticonazole (EC₅₀ = 11.631 mg/L) is slightly toxic to this plant. The results obtained with the computational tools TEST, ADMETLab2.0 and admetSAR2.0 also show that metconazole and tetraconazole are toxic to other aquatic organisms: Pimephales promelas, Daphnia magna and Tetrahymena pyriformis. A molecular docking study shows that triazole fungicides can affect photosynthesis in Lemna minor because they strongly bind to C43 (binding energies between −7.44 kcal/mol and −7.99 kcal/mol) and C47 proteins (binding energies between −7.44 kcal/mol and −8.28 kcal/mol) in the reaction center of photosystem II, inhibiting the binding of chlorophyll a to these enzymes. In addition, they can also inhibit glutathione S-transferase, an enzyme involved in the cellular detoxification of Lemna minor.

Triticonazole is a fungicide used to control diseases in numerous plants. The commercial product is a racemate containing (R)- and (S)-triticonazole and its residues have been found in vegetables, fruits, and drinking water. This study considered the effects of triticonazole on soil microorganisms and enzymes and human health by taking into account the enantiomeric structure when applicable. An experimental method was applied for assessing the effects of triticonazole on soil microorganisms and enzymes, and the effects of the stereoisomers on soil enzymes and human health were assessed using a computational approach. There were decreases in dehydrogenase and phosphatase activities and an increase in urease activity when barley and wheat seeds treated with various doses of triticonazole were sown in chernozem soil. At least 21 days were necessary for the enzymes to recover the activities. This was consistent with the diminution of the total number of soil microorganisms in the 14 days after sowing. Both stereoisomers were able to bind to human plasma proteins and were potentially inhibitors of human cytochromes, revealing cardiotoxicity and low endocrine disruption potential. As distinct effects, (R)-TTZ caused skin sensitization, carcinogenicity, and respiratory toxicity. There were no significant differences in the interaction energies of the stereoisomers and soil enzymes, but (S)-TTZ exposed higher interaction energies with plasma proteins and human cytochromes.