RT Journal Article
SR Electronic
T1 Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 750
OP 755
VO 22
IS 5
A1 T Mizutani
A1 K Yoshida
A1 S Kawazoe
YR 1994
UL http://dmd.aspetjournals.org/content/22/5/750.abstract
AB The metabolism of three nephro- or hepatotoxic thiazoles--2-(thiazol-4-yl)benzimidazole (thiabendazole) (1a), 4-tert-butyl-2-methyl-thiazole (1b), and 2-(p-methoxyphenyl)-4-methylthiazole (1c)--was examined in mice with special regard to the formation of ring cleavage products. By GC/MS analyses of derivatized metabolites and comparison with authentic samples, thioformamide and benzimidazol-2-ylglyoxal as the accompanying fragment were identified as urinary metabolites in mice dosed with 1a. Similarly, 1b produced thioacetamide and tert-butylglyoxal, and 1c produced p-methoxy-thiobenzamide (and its S-oxide) and methylglyoxal. These results could be explained by the postulated metabolic pathways where thiazoles would undergo microsomal epoxidation of the C = C double bond and, after being hydrolyzed, the resulting epoxide would then be decomposed to form the corresponding thioamides and alpha-dicarbonyl fragments.