Studies on the fate of thiabendazole(TBZ) in mice. II. Distribution of TBZ, 5-hydroxythiabendazole including its conjugates and the changes of liver microsomal drug-metabolizing enzyme activities in pregnant mice fed TBZ orally.

Abstract

Thiabendazole (TBZ) suspended in olive oil or 3% gum arabic was given orally to pregnant ICR mice on d 15 or during d 6-15 of gestation at a dose of 1300 mg/kg/d, and TBZ including its metabolites, 5-hydroxythiabendazoles (5-OH TBZ and its conjugates) and the activities of the liver microsomal drug metabolizing enzymes were analyzed. The concentration of 5-OH TBZ was higher than that of its conjugates (glucuronide and sulfate) in the liver and placenta, whereas the levels of the conjugates were greater than that of the free form in the kidney 1 or 25 h after a single or repetitive administration of TBZ. Little sulfate of 5-OH TBZ was detected in the fetus. Aniline hydroxylase activity increased significantly after repetitive and a single administration (25 h after) of TBZ. The amount of cytochrome P-450 also increased significantly after repetitive administration of TBZ. Two vehicles (olive oil and 3% gum arabic) showed no significant difference in the data obtained above.