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.

The present study focuses on predicting the pharmacokinetics and toxicological endpoints of the widely used intensive sweeteners for preventing and management of diabetes: acesulfame K, advantame, aspartame, cyclamates, glycyrrhizin, neohesperidin dihydrochalcone, neotame, saccharin, steviol, sucralose, and tagatose. Predictions obtained using several computational tools were generally in good agreement each other and with few known data concerning the effects of these compounds on humans. The possible side effects produced by these sweeteners are: h-ERG blocking potential (glycyrrhizin, neohesperidin dihydrochalcone, advantame), eye and skin injuries (acesulfame K, cyclamates, saccharine), hepatotoxicity (saccharine), nephrotoxicity (steviol, glycyrrhizin), hypotension (advantame), mutagenicity and genotoxic carcinogenicity (acesulfame K, sucralose). RezumatPrezentul studiu se concentrează pe predicția profilurilor farmacocinetice și a efectelor toxicologice ale principalilor îndulcitori folosiți pentru prevenirea și gestionarea diabetului zaharat: acesulfam K, advantam, aspartam, ciclamați, glicirizină, neotam, neohesperidină, steviol, sucraloză, tagatoză și zaharină. Predicțiile obținute folosind mai multe instrumente computaționale au fost în general în concordanță și cu puținele date cunoscute cu privire la efectele acestor compuși asupra oamenilor. Posibilele efecte secundare produse de utilizarea îndulcitorilor investigați sunt: cardiotoxicitate prin inhibiția canalului de potasiu în mușchiul cardiac (glicirizina, neohesperidina, advantamul), leziuni oculare și cutanate (acesulfam K, ciclamați, zaharina), hepatotoxicitate (zaharina), nefrotoxicitate (steviolul, glicirizina), hipotensiune (advantamul), mutagenicitate și carcinogenitate genotoxică (acesulfam K, sucraloza).

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.

This review provides the summarized current knowledge on the degradation and effects on the non-target organisms from soil and aquatic environment of the triazole fungicides approved to be used in most of the European Union also taking into account stereospecific differences. Synthetized data reveal that triazole fungicides are usually persistent in aqueous environment and soil, and manifest moderately acute and chronic toxicity against the organisms living in these environments. Furthermore, the enantiomers of triazole fungicides proved to have distinct distribution and effects on these environments. These data are important for assuring a sustainable agriculture by production and use of single-stereoisomer and/or encouraging a management of agricultural crops with minimum effects on environment.

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.