Pillai_1993_Pestic.Biochem.Physiol_45_141

Carbofuran was selected to model the pulmonary disposition of a carbamate anticholinesterase insecticide. Lungs were isolated from male Sprague-Dawley rats and placed in an artificial recirculating thoracic chamber maintained at 37degC. Lungs were exposed to 0.01 mM carbofuran in the perfusate and evaluated at selected time points for 1 hr. Perfusate samples and postperfusion lung homogenates were extracted and then analyzed for carbofuran and major metabolites using high-pressure liquid chromatography (C18 reverse-phase column). Lung acetylcholinesterase activity (AChE) was measured at 5, 30, and 60 min postexposure. Limited carbofuran metabolism (11% of administered dose) occurred during the 1-hr exposure period. Major metabolites were the oxidative metabolite, 3-hydroxy carbofuran (8% of administered dose), and the hydrolytic metabolite carbofuran phenol (3% of administered dose). Both of these metabolites were present only as the glucuronide conjugate in the perfusate. Pharmacokinetic analysis of carbofuran perfusate levels during the 1-hr exposure indicated a one-compartment model with slow elimination (k = 0.0043 min-1 and t1/2 = 161.16 min). AChE was inhibited by 29, 61, and 64%, respectively. Results indicated that the lung AChE was significantly inhibited and the extent of inhibition was related to limited carbofuran metabolism and clearance by the lung.