Carbofuran metabolism and toxicity in the rat.
The influence of carbofuran metabolism on acetylcholinesterase inhibition has been defined after low dose (50 micrograms/kg, iv and oral) [carbonyl-14C]carbofuran exposures to male Sprague-Dawley rats. Red blood cell acetylcholinesterase (RBC AchE) inhibition (83% at 2 min, 37% at 15 min for iv and oral, respectively, with recovery by 3 hr), was correlated with carbofuran plasma concentrations (r = 0.97). Eight-hour sample collection indicated that ultimate carbofuran fate (41-47% 14CO2, 14-15% urine, less than 1% feces, and 30-31% carcass) was independent of exposure route. Carbofuran absorption (peak plasma levels less than 7 min), distribution, and elimination (t1/2 = 29 +/- 5 min) occurred rapidly. 3-Hydroxycarbofuran, a significant oxidative metabolite of carbofuran with anticholinesterase activity, was rapidly formed and subject to enterohepatic circulation (plasma t1/2 = 64 +/- 5 min). Results indicated that rapid RBC AchE recovery closely paralleled carbofuran metabolism and the primary in vivo disposition of 3-hydroxycarbofuran was metabolic conjugation.
D000110:Acetylcholinesterase / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D002235:Carbofuran / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D002800:Cholinesterase Inhibitors; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D007275:Injections, Intravenous; D007306:Insecticides / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution
D002800:Cholinesterase Inhibitors; D007306:Insecticides; C028403:3-hydroxycarbofuran; D000110:Acetylcholinesterase; D002235:Carbofuran