A structure-activity relationship for the neurotoxicity of triazole fungicides.
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.
Crofton
K M
KM
Neurotoxicology Division, National Health Effects and Environmental Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
D000818:Animals; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000633:toxicity*; D006948:Hyperkinesis / Q000139:chemically induced*; D008297:Male; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D005659:Fungicides, Industrial; D014230:Triazoles; C032910:triadimefon