• Journal Article

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

Citation

Mathews, J., Brown, S., Patel, P., Black, S. R., Banks, T. T., Etheridge, A., ... Waidyanatha, S. (2013). Metabolism and disposition of [(14)C]n-butyl-p-hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application. Xenobiotica, 43(2), 169-181. DOI: 10.3109/00498254.2012.702935

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