Enantioselective metabolism of triadimefon and its chiral metabolite triadimenol in lizards

Abstract

Chinese lizards (Eremias argus) were exposed to separated R-(-)-triadimefon, S-(+)-triadimefon and racemic triadimefon to evaluate enantioselective accumulation of triadimefon. After single oral administration of R-(-)-triadimefon, S-(+)-triadimefon and racemic triadimefon, the time-concentration curves in different tissues were found to be different. Triadimefon enantiomers crossed the blood-brain barrier and brain is a main target organ. The residues of triadimefon enantiomers in fat were highest after 24h indicating that fat was the main tissue of accumulation. In racemic triadimefon exposure group, the enantiomer fractions of R-(-)-triadimefon in different tissues showed that the differences between R-(-)-triadimefon and S-(+)-triadimefon were significant in absorption and metabolism, but the differences became smaller in exclusion and accumulation. From the results of mathematical models, S-(+)-triadimefon was absorbed and eliminated faster than R-(-)-triadimefon, and R-(-)-triadimefon was easily distributed in the tissues and more easily converted into its metabolites. Furthermore, among the four enantiomers of triadimenol, SR-(-)-triadimenol produced by S-(+)-triadimefon may have the highest fungicidal activity and the strongest biological toxicity, RR-(+)-triadimenol produced by R-(-)-triadimefon was most likely to bioaccumulate in lizard. Identifying toxicological effects and dose-response relationship of SR-(-)-triadimenol and RR-(+)-triadimenol will help fully assess the risk of TF enantiomers use in the future. The results enrich and supplement the knowledge of the environmental fate of triadimefon enantiomers.

Absolute Configuration, Enantioselective Bioactivity, and Degradation of the Novel Chiral Triazole Fungicide Mefentrifluconazole

“…Four bitertanol stereoisomers also had different environmental behaviors and biological effects. , (−)-Hexaconazole showed 6-fold more toxicity than (+)-hexaconazole against Scenedesmus obliquus . Triadimefon and its chiral metabolite triadimenol showed enantioselective metabolism in lizards . Li et al found that (−)-fenbuconazole was preferentially degraded in soil, and the metabolites of fenbuconazole also exhibited significant enantioselectivity .…”

Triadimefon in Aquatic Environments: Occurrence, Fate, Toxicity and Risk

“…Metabolic rates of RS-TDN and RR-TDN were more rapid than that of SR-TDN and SS-TDN, respectively. S-TDF was absorbed faster than R-TDF, and R-TDF was easily metabolism to TDN in lizards [51]. However, in vitro in Rainbow trout (Oncorhynchus mykiss), S-TDF was more easily transformed to triadimenol than R-TDF [53], which illustrated that species differences in stereo-selective metabolism of triadimefon.…”

Form and Function of the Vertebrate and Invertebrate Blood-Brain Barriers

“…As for other vertebrate taxa, toxins have variable effects on BBB integrity, and in some cases, can cross the BBB. For example, the fungicide triadimefon crosses the BBB of the Chinese lizard (Eremias argus), entering the neural tissue of the brain [134]. Cadmium crosses the BBB and alters glial structure in the brain of the Italian wall lizard Podarcis siculus [133].…”