title: Metabolism and disposition of [14C]n-butyl-p-hydroxybenzoate in male and female Harlan Sprague Dawley rats following oral administration and dermal application.
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.
authors: Department of Pharmacology and Toxicology, RTI International, Research Triangle Park, NC, USA.
authors: James M
authors: JM
authors: Mathews
authors: Sherri S
authors: SS
authors: Brown
authors: Purvi R
authors: PR
authors: Patel
authors: Sherry R
authors: SR
authors: Black
authors: Troy T
authors: TT
authors: Banks
authors: Amy S
authors: AS
authors: Etheridge
authors: Timothy R
authors: TR
authors: Fennell
authors: Rodney W
authors: RW
authors: Snyder
authors: Chad R
authors: CR
authors: Blystone
authors: Suramya
authors: S
authors: Waidyanatha
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes / Q000652:urine; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010226:Parabens / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D010226:Parabens; D015262:Xenobiotics; C038091:butylparaben