Metabolism of N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6- tetrahydrophthalimide (S-23121) in the rat. II. Absorption, disposition, excretion and biotransformation.
1. To examine the metabolic fate of N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6- tetrahydrophthalimide (S-23121), rats were given a single oral dose of [phenyl-14C]S-23121 at 1 or 250 mg/kg. 2. The radiocarbon was almost completely eliminated from the rat within 7 days after administration for both dose groups. Faecal 14C-excretion was major (71-86% of the dose) and urinary 14C-excretion was minor (18-30%). 3. 14C-tissue residues on the seventh day after administration were generally very low. Peak 14C-concentrations in the kidney and liver occurred 4 h after administration and decreased rapidly thereafter. Amounts (percentage of dose) of the parent compound in faeces were 13-26% for low dose, and 22-35% for high dose. 4. The major metabolites in faeces were sulphonic acid conjugates (13-20% of the administered dose), formed by incorporation of a sulphonic acid group into the double bond of the tetrahydrophthalimide. The major metabolites in urine were sulphates and glucuronides of 4-chloro-2-fluoro-5-hydroxyaniline, amounting to 5-7 and 2-3% of the administered dose, respectively. Sulphonic acid conjugates were not detected in urine, blood, kidney or liver.
Yoshino
H
H
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Kaneko
H
H
Nakatsuka
I
I
Yamada
H
H
D000818:Animals; D002855:Chromatography, Thin Layer; D005243:Feces; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D010797:Phthalimides / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D006540:Herbicides; D010797:Phthalimides; C083440:S 23121