Biochemical studies on phthalic esters. IV. Metabolism of diheptyl phthalate in rats

Excretion, organ distribution, and metabolism of di(5-methylhexyl) phthalate (DMHP) were studied in male rats. Orally administered 14C-DMHP was rapidly absorbed and 60 and 30%, respectively, of the radioactivity were found excreted into the urine and feces after 7 days. Biliary excretion amounted to about 15% of the dose after 4 days. No specific high concentrations were found in the organs and tissues. Four major metabolites were isolated by HPLC from the ethyl acetate extract of the urine. All of these compounds were monoesters and determined as 5-hydroxy-5-methylhexyl phthalate, 6-hydroxy-5-methylhexyl phthalate, 5-carboxyhexyl phthalate, and 3-carboxypropyl phthalate by spectral analysis (MS, 1H NMR, 13C NMR, UV, IR, etc.). Unchanged DMHP and mono-5-methylhexyl phthalate (MMHP) were found together with a small amount of phthalic acid in the feces. MMHP and its glucuronide conjugate were detected in the bile.