Conjugation: the Major Metabolic Pathway of 14C-diflubenzuron in the House Fly13

Abstract

Diflubenzuron, (N-[[(4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide), uniformly labeled with carbon-14 in both rings, was used in the study of its metabolism in Musca domestica L. Seventy-two h after injection of 2684 dpm/fly, the distribution of radioactivity was 78.4% in treated flies of which 74% was unchanged diflubenzuron and 4.4% was diflubenzuron conjugate, and 16.5% in the excreta of which all radioactivity was accounted for by diflubenzuron conjugates. Percentages were calculated on the basis of the total injected amount. Upon hydrolysis of the excreta extract in 1 N HCl at 80°C for 3–5 h, the diflubenzuron conjugates yielded a single nonpolar compound that accounted for 70% of radioactivity and one unknown polar compound that accounted for 30% of radioactivity. This nonpolar compound isolated from acid hydrolysis of the excreta was identified as N-[[(4-chloro-2-hydroxyphenyl)amino]carbonyl]-2,6-difluorobenzamide. The house flies were unable to cleave the diflubenzuron molecule between the carbonyl and amide groups of the urea bridge. The intact diflubenzuron molecule reacted at the 2 position of the aniline ring to form more than one conjugate with normal fly constituents, which were immediately excreted as polar compounds. The diflubenzuron conjugates were stable to alkaline conditions, soluble in water or acetonitrile, and insoluble in acetone.