Metabolism of triallate in Sprague-Dawley rats. 2. Identification and quantitation of excreted metabolites

Abstract

Triallate was administered orally to Sprague-Dawley rats. Twelve excreted metabolites were identified, the most abundant being 2,3,3-trichloro-2-propenesulfinic acid. Five metabolites derived from 2,3,3-trichloro-2-propenethiol were identified in excreta, including a methyl sulfone mercapturate whose structure was confirmed by X-ray crystallography. Three 2-chloroacrylate metabolites were identified, including a 2-chloroacrylate mercapturate whose structure was confirmed by X-ray crystallography. 2,3,3-Trichloro-2-propenol and hydroxytriallate were also identified as metabolites. Dosing of radiolabeled thiol and sulfinic acid to separate animals resulted in excretion of only thiolderived metabolites in the urine of thiol-dosed rats, while sulfinic acid and sulfonic acid were excreted by sulfinic acid-dosed rats. Triallate metabolism in rats proceeds via three main pathways, i.e., S-oxidation leading to sulfur acids, S-oxidation/hydrolysis/reduction leading to thiol derivatives, and C-oxidation of the 2,3,3-trichloropropenethioI moiety. This study demonstrates that formation of readily excreted sulfur acids and thiol derivatives is the major route of triallate metabolism in rats.

IN VITRO METABOLISM OF MK-0767 [(±)-5-[(2,4-DIOXOTHIAZOLIDIN-5-YL)METHYL]-2-METHOXY-N-[[(4-TRIFLUOROMETHYL)-PHENYL] METHYL]BENZAMIDE], A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR α/γ AGONIST. II. IDENTIFICATION OF METABOLITES BY LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

“…This mechanism was proposed for the TZD ring opening of troglitazone by Kassahun et al (2001). A similar mechanism was also proposed by Hackett et al (1993) and Nadeau et al (1993) for the metabolism of the herbicide, triallate. Direct oxidation of M22 to give M7, although possible, was not detected when M22 was incubated with NADPH-fortified liver microsomes.…”

Metabolism of triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways

“…Thiol 4 was formed early in the course of microsomal and S-9 incubations and was then consumed, most likely via oxidation to the sulfur acids 2 and 3. In vitro metabolite 4 displayed the same HPLC retention time relative to triallate as did an authentic standard (Nadeau et al, 1993). Thiol 4 was isolated from a quenched S-9 incubation mixture by extraction with ethyl acetate and was derivatized to a pentafluorobenzoic acid thioester using pentafluorobenzoyl chloride.…”

Metabolism of triallate in Sprague-Dawley rats. 1. Material balance, tissue distribution, and elimination kinetics

“…The a phase reflects elimination as well as absorption, distribution, and metabolism, and changes in these processes at the high-dose level would be reflected in a longer initial half-life of elimination. Differences in triallate metabolite distribution are also observed at the 5 and 500 mg/kg dose levels (Nadeau et al, 1993). The ß phase half-life is considerably longer than the a phase half-life for all groups (Table III).…”

“…Unlabeled triallate used for dilution to the desired specific activity had a purity of 99%. Test materials were synthesized in the laboratories of Monsanto Agricultural Co., St. Louis, MO (Nadeau at al., 1993). Purchased chemicals were of reagent or scintillation grade.…”

“…The present paper describes the material balance, tissue distribution, and elimination kinetics in Sprague-Dawley rats orally dosed with isotopically labeled triallate. The following paper in this issue (Nadeau et al, 1993) describes the chemical identification of urinary and fecal metabolites excreted by these animals and outlines possible metabolic pathways accounting for metabolite formation. The final paper in this series (Hackett et al, 1993) describes an in vitro study of triallate metabolism using microsomal enzyme preparations obtained from Sprague-Dawley rats and provides a detailed mechanistic understanding of the formation and reactions of metabolic intermediates giving rise to observed in vivo rat metabolites.…”