Pharmacokinetics, metabolism and toxicity of the plant-derived photoxin alpha-terthienyl.
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.
Marles
R
R
Ottawa-Carleton Institute of Chemistry, University of Ottawa, Ont., Canada.
Durst
T
T
Kobaisy
M
M
Soucy-Breau
C
C
Abou-Zaid
M
M
Arnason
J T
JT
Kacew
S
S
Kanjanapothi
D
D
Rujjanawate
C
C
Meckes
M
M
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D013876:Thiophenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine
D007306:Insecticides; D013876:Thiophenes; C019101:alpha-terthienyl; C103889:1,4-di(2'-thienyl)-1,4-butadione; C103890:2,2'-bithiophene-5-carboxylic acid