Metabolism of the insecticide teflubenzuron in rats.
1. The metabolic fate of the insecticide teflubenzuron, orally dosed to the male Wistar rat, was investigated. Particular attention was paid to the metabolic fate of the benzoyl and aniline moiety after hydrolysis of the urea bridge. 2. The 0-48-h urinary and faecal metabolic patterns and recoveries showed that for a dose range of 4-53 mumol (1.5-20 mg) teflubenzuron, 90% of the dose was excreted in the faeces mainly in unmodified form, approximately 4.6% was absorbed from the lumen and excreted in the urine, and 5.4% was retained in the body. Metabolites excreted in the urine could be identified as benzoate and aniline derivatives originating from the two aromatic rings of teflubenzuron liberated from the parent molecule by hydrolysis of the urea bridge. 3. The amount of urinary benzoate-type metabolites was about eight times the amount of aniline-type metabolites, indicating significant differences in efficiency of urinary excretion of the benzoate moiety as compared with the aniline ring. 4. To investigate further the possible reason underlying this difference in urinary excretion efficiency between the two aromatic derivatives formed from teflubenzuron, dose-recovery studies of these aniline- and benzoate-type metabolites were performed. These studies confirmed the discrepancy observed between the urinary recovery of the benzoyl and the aniline moiety of teflubenzuron. 5. Additional results of the present study indicate that the above discrepancy can be explained by the fact that the benzoate derivative is excreted mainly in its unmetabolized form, whereas the aniline derivative needs additional phase I and II modifications before it can be excreted from the body, the former being a relatively slow reaction. Furthermore, conversion of the halogenated aniline derivative in phase I metabolism might result in a reactive benzoquinone-type or N-oxidized primary metabolite, which can be retained in the body due to reaction with cellular macromolecules.
Koerts
J
J
Department of Biochemistry, Agricultural University Wageningen, The Netherlands.
Soffers
A E
AE
De Kraker
J W
JW
Cnubben
N H
NH
Rietjens
I M
IM
D000813:Anilides / Q000652:urine; D000814:Aniline Compounds / Q000652:urine; D000818:Animals; D001549:Benzamides / Q000378:metabolism* / Q000652:urine; D001565:Benzoates / Q000652:urine; D005243:Feces / Q000737:chemistry; D006868:Hydrolysis; D007306:Insecticides / Q000378:metabolism* / Q000652:urine; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C109957:3,5-dichloro-2,4-difluoroaniline; D000813:Anilides; D000814:Aniline Compounds; D001549:Benzamides; D001565:Benzoates; D007306:Insecticides; C077004:2,6-difluorobenzoic acid; C052595:teflubenzuron; C023650:aniline; C078231:2,6-difluorobenzamide