PT  - JOURNAL ARTICLE
AU  - T Mizutani
AU  - K Yoshida
AU  - S Kawazoe
TI  - Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products.
DP  - 1994 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 750--755
VI  - 22
IP  - 5
4099  - http://dmd.aspetjournals.org/content/22/5/750.short
4100  - http://dmd.aspetjournals.org/content/22/5/750.full
SO  - Drug Metab Dispos1994 Sep 01; 22
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.