A structure-activity relationship for the neurotoxicity of triazole fungicides

Abstract

Previous work has demonstrated that acute exposures to the triazole fungicide triadimefon affects central nervous system (CNS) catecholamines and induces a transient syndrome in rats that consists of hyperactivity and stereotyped behaviors. The present research was designed to determine whether this type of CNS toxicity is characteristic of other triazoles. Dose-effect functions were determined for 14 different triazoles or structurally related pesticides in adult male Long-Evans rats. All chemicals were administered per os in corn oil. Hyperactivity was measured for 2 h in figure-eight mazes. Results indicated that only triadimefon and triadimenol were able to induce hyperactivity; none of the other chemicals produced this effect. These data suggest a very rigid structure-activity relationship (SAR) for the hyperactivity syndrome and indicate that CNS effects may be minimized in the future design of triazoles without impacting fungicidal efficacy.