Percutaneous absorption, disposition, and excretion of 4,4'-methylenebis(2-chloroaniline) in dogs.
Percutaneous (pc) absorption, disposition, and excretion of 14C-MBOCA (4,4'-methylenebis(2-chloroaniline) ) were investigated in male beagle-type dogs by HPLC and compared to intravenously (iv) administered controls. Following application of 115 muCi MBOCA to a 25 cm2 area of the skin, no measurable radioactivity was detected in blood for the subsequent 24-hr period, but 14C-MBOCA and metabolites were excreted in urine and bile. During the 24-hr collection period, a total of 1.3% of the administered dose was recovered in the urine (0.4% of which was unchanged MBOCA). At 24 hr 0.62% of the dose was recovered in gallbladder bile. Approximately 90% of the administered dose was recovered in skin at the application site. Liver, kidney, and fat were the tissues with highest radioactivity. After a bolus iv injection, MBOCA disappeared rapidly from blood (t 1/2 beta = 0.70 hr). In the 24 hr following iv injection, 46% of the administered dose was excreted in urine (0.54% of which was unchanged MBOCA). At 24 hr 32% of the dose was recovered in gallbladder bile. Tissue radioactivity was 10-20 X higher after iv than pc administration and highest in liver, kidney, fat, and lung. The results demonstrated in a canine model that skin absorption was a viable route of entry for MBOCA and that unmetabolized MBOCA was a small percentage (0.4-0.5%) of the total urinary excretion. MBOCA was rapidly and extensively metabolized and excreted in urine and bile following both iv and pc administration.
D000818:Animals; D001559:Benzhydryl Compounds / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008753:Methylenebis(chloroaniline) / Q000008:administration & dosage / Q000378:metabolism*; D012869:Skin Absorption; D014018:Tissue Distribution
D001559:Benzhydryl Compounds; D002250:Carbon Radioisotopes; D008753:Methylenebis(chloroaniline)