Pharmacokinetics, Metabolism and Toxicity of the Plant‐Derived Photoxin α‐Terthienyl

Abstract

The plant-derived insecticide, alpha-terthienyl was prepared by synthesis as 3',4'-di[14C]-alpha-terthienyl for pharmacokinetic and metabolism studies. When administered orally to rats at a single dose of 50 mg/kg, excretion of the labelled material was maximal one day after administration and declined to no measurable quantities by day 4. Two metabolites [1,4-di(2'-thienyl)1,4-butadione and 2-2'-bithiophene-5-carboxylic acid] and trace quantities of the parent material were isolated from the urine and chemically identified. These represent the first metabolites of alpha-terthienyl identified. In pilot acute and subacute trials, unlabelled alpha-terthienyl was non-toxic when administered orally to rats as the "ready to use" formulation (0.1% active ingredient). The pure compound had an LD50 of 110 mg/kg when administered intraperitoneally to rats. The results suggest that there is considerable separation with respect to mosquito larvae and non-target mammal sensitivity.