The sex-specific sulfation of the major metabolite of the novel fungicide cyprodinil in the rat

✍ Scribed by Müller, Thomas; Thanei, Peter; Mücke, Wolfgang; Kriemler, Hans-Peter; Winkler, Tammo

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 72 KB
• Volume: 55
• Category: Article
• ISSN: 1526-498X
• DOI: 10.1002/(sici)1096-9063(199905)55:5<594::aid-ps960>3.0.co;2-x

✦ Synopsis

The metabolism of cyprodinil, a novel broad-spectrum fungicide, was investigated in rats. After single oral administration of 0.5 or 100 mg kg À1 body weight, [phenyl-U-14 C]cyprodinil was rapidly eliminated, principally in the urine. The metabolite pattern in urine exhibited a signi®cant sex-related difference with respect to the major metabolite. Males and females both produced a dihydroxy metabolite, N-4-(hydroxyphenyl)-4-cyclopropyl-5hydroxy-6-methylpyrimidin-2-ylamine.

Female rats conjugated this metabolite with sulfate exclusively at the 5-hydroxypyrimidinyl moiety, while males formed equal amounts of the monosulfate and a disulfate conjugate. The sex dimorphism in the conjugation reaction indicates the involvement of a sex-speci®c sulfotransferase that catalyzed the transfer of the second sulfate group.