The study on the biological fate of paraben at the dose of practical usage in rat. I. The metabolism and excretion of ethyl p-hydroxybenzoate (ethyl paraben) and p-hydroxybenzoic acid.

Abstract

The biological fates of ethylparaben (EP) which was used as a preservative for the pharmaceutical preparations and foods, and p-hydroxybenzoic acid (HB), which is the parent compound of EP, were studied at the dose of practical usage (2 mg/kg) in rats. Both EP and HB were metabolized to glycine conjugate (M1), ester type glucuronide (M3) and sulfate (M4) of HB and excreted in the urine and bile, the excretion ratios were different as compared with the results of higher dose experiments and a route dependency was found in the rate of excretion in the bile. In i.v. administration of EP, the excreted total activity was 91.3% per dose in the urine and 5.97% in the bile, and percentages per dose of the major metabolites excreted in the urine were 8.14% of HB, 39.6% of M1, 29.5% of M3 and 6.48% of M4. In intraduodenal administration of EP, the excreted total activity (83.5%) and the activity excreted as HB (3.51%) decreased compared with the i.v. administration. In the HB administration, the route dependency of the total activity was not found, but a decrease in the excretion of HB in the intraduodenal administration was found. The excretion of total radioactivity almost ceased by 5 h and the biological half-lives obtained from the .beta.-phase of the sigma-minus plots of the metabolites excreted in the urine were 40-70 min. The result obtained in this study differ from those at the high dose experiments.