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.