Metabolism of Flutolanil in Rats

Abstract

The radiocarbon in [aniline ring-14C(U)]flutolanil, 3/-isopropoxy-2-(trifluoromethyl)-benzanilide, orally administered to male rats at the dose of 20 (or 100) mg/kg was rapidly and almost completely excreted into urine and feces, 69 and 26 (or 67 and 30)% of the dose, respectively, within 72 hr, although no radiocarbon was found in the expired C02. Radiocarbon level in the blood reached the maximum of 4.2 (or 12.5) μg 14C-flutolanil equivalent/ml 2 hr after administration, and then rapidly decreased. None of the tissues examined had a high residual radioactivity 72 hr after administration (20 mg/kg). Small amounts of flutolanil were recovered from both of urine and feces (2.3 and 1.2% of the dose 20 mg/kg, respectively). In the case of 20 mg/kg, four metabolites identified were 3’-(l-hydroxycarbo-nylethoxy)-2-(trifluoromethyl)benzanilide (3), 4/-hydroxy-3/-isopropoxy-2-(trifluoromethyl)-benzanilide (4), 3/-hydroxy-2-(trifluoromethyl)benzanilide (5) and 4,-hydroxy-3/-methoxy-2-(trifluoromethyl)benzanilide (8). Their D-glucuronide and/or sulfate conjugates were also detected. The major metabolites were free and conjugated 5, which accounted for 57.5% of the dose (51% in urine and 6.5% in feces). Those in bile accounted for 20% of the dose (20 mg/kg), much exceeding the fecal level. This should indicate the deconjugation, reabsorption and resulting exclusive excretion into urine as the sulfate. Metabolism of flutolanil in rats occurs through oxidative O-dealkylation and following conjugation. 4/-Hydroxylation also occurs but is not predominant. There was no evidence for cleavage of the anilide bond or hydroxylation on the 2-(trifluoromethyl)benzoyl ring. © 1983, Pesticide Science Society of Japan. All rights reserved.