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.
D000818:Animals; D003993:Dibutyl Phthalate / Q000378:metabolism* / Q000633:toxicity; D004950:Esterases / Q000037:antagonists & inhibitors*; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000201:enzymology*; D008297:Male; D063086:Organothiophosphates / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D010795:Phthalic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D010795:Phthalic Acids; D003993:Dibutyl Phthalate; C006863:butyl phosphorotrithioate; D004950:Esterases