The effect of intestinal esterase inhibition on the in vivo absorption and toxicity of Di-n-butyl phthalate.

Inhibition of intestinal mucosal esterases by S,S,S-tributylphosphorotrithioate (DEF) did not alter the gastro-intestinal absorption of di-n-butyl phthalate (DBP) in the rat. After intragastric administration of [14C]DBP to control and esterase-inhibited animals, the disappearance of 14C from the small intestine and the levels of 14C in the blood were not significantly different in the two groups over the first 4 hr. Peak blood levels of 14C occurred 2 hr after dosing in both groups of rats. The circulating [14C]butyl phthalate in the diester form accounted for less than 5% of the total 14C at 2 hr, regardless of intestinal esterase activity. The remaining 14C was associated with mono-n-butyl phthalate or more polar metabolites. These data suggest an important role for pancreatic esterases, which may be protected from DEF-mediated inhibition by storage in zymogen granules, in the metabolism and absorption of DBP.