[Biotransformation of monolinuron (N-(4-chlorophenyl)-N'-methyl-N'methoxyurea) in isolated perfused chicken liver]

The biotransformation of radioactively labelled monolinuron (N-(4-chloro[U-14C]phenyl)-N'-methyl-N'-methoxyurea) was studied in the isolated perfused liver of the chicken. After a 4-hr perfusion, 83.1% of the added radioactivity was recovered, 56.6% in the perfusion medium and 26.5% in the liver and bile. The fraction of radioactivity extractable from the perfusion medium into ethyl acetate amounted to 47.8% of the added dose. In addition to monolinuron, five breakdown products were identified in this extract, namely N-(4-chlorophenyl)-N'-hydroxymethyl-N'-methoxyurea, N-(4-chlorophenyl)-N'-methoxyurea, N-(4-chlorophenyl)-N'-methylurea, 4-chlorophenylurea and 4-chloroacetanilide. Of particular interest was the absence of arylhydroxylated monolinuron derivatives, since in monolinuron-metabolism studies in the laying hen 2-hydroxy-4-chlorophenylurea and 3-hydroxy-4-chlorophenylurea were both detected. This differing metabolism corresponds to earlier findings in the rat, in which arylhydroxylated breakdown products were detected only in in vivo studies and not in rat-liver perfusion. Possible reasons for the differing metabolism of monolinuron in vivo and in vitro are discussed.