Metabolism and disposition of [14C]n-butyl-p-hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application

Xenobiotica. 2013 Feb;43(2):169-81. doi: 10.3109/00498254.2012.702935. Epub 2012 Jul 25.

Abstract

n-Butyl-p-hydroxybenzoate (n-butylparaben, BPB) is an antioxidant used in foods, pharmaceuticals and cosmetics. This study investigated the disposition of ring-labelled [(14)C]BPB in Harlan Sprague Dawley rats, and in rat and human hepatocytes. BPB was rapidly cleared in hepatocytes from rat (t(1/2) = 3-4 min) and human (t(1/2) = 20-30 min). The major metabolites detected in rat hepatocytes were hydroxybenzoic acid and in human hepatocytes were hydroxybenzoic acid and hydroxyhippuric acid. [(14)C]BPB was administered to male rats orally at 10, 100 or 1000 mg/kg, intravenously at 10 mg/kg and dermally at 10 and 100 mg/kg; female rats were administered oral doses at 10 mg/kg. Oral doses of BPB were well-absorbed (>83%) and eliminated chiefly in urine (83-84%); ≤ 1% of the radioactivity remained in tissues at 24 h or 72 h after dosing. About 4% and 8%, respectively, of 100 mg/kg dermal doses were absorbed in 24 h and 72 h, and about 50% of a 10 mg/kg dose was absorbed in 72 h. Metabolites detected in urine included those previously reported, BPB-glucuronide, BPB-sulfate, hydroxybenzoic acid and hydroxyhippuric acid, but also novel metabolites arising from ring hydroxylation followed by glucuronidation and sulfation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Carbon Radioisotopes / urine
  • Female
  • Hepatocytes / metabolism*
  • Humans
  • Injections, Intravenous
  • Male
  • Parabens / administration & dosage
  • Parabens / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Xenobiotics / administration & dosage
  • Xenobiotics / metabolism*

Substances

  • Carbon Radioisotopes
  • Parabens
  • Xenobiotics
  • butylparaben