title: Disposition of single oral doses of butylated hydroxytoluene in man and rat.
abstract: The kinetics and metabolism of butylated hydroxytoluene (BHT) in man and rats have been compared. Single oral doses of 200, 63 or 20 mg BHT/kg body weight were administered to rats and a single oral dose of 0.5 mg/kg body weight was ingested by human volunteers (non-smoking males). In rats, kinetic parameters (area under the plasma concentration-time curve, plasma BHT peak levels) showed a dose-dependent increase. Plasma BHT levels after oral administration were about four times higher than those that have been reported for another synthetic food antioxidant, butylated hydroxyanisole (BHA; Verhagen et al., Fd Chem. Toxic. 27, 151-158). This may be a reflection of a smaller volume of distribution for BHT, since there were no differences in plasma elimination half-life or plasma clearance between BHT and BHA. In man, the mean plasma concentration-time profile after oral BHT intake was well below the BHT profiles observed for rats and closely followed plasma BHA kinetics in man. In rats, the simultaneous administration of BHT (200 mg/kg body weight) and BHA (200 mg/kg) significantly decreased the absorption of BHT from the gastro-intestinal tract in the first few hours after treatment; the plasma kinetics of BHA were not influenced by the simultaneous administration of BHT. In human female volunteers no alterations in plasma BHT or BHA profiles were seen after the simultaneous ingestion of BHT (0.25 mg/kg body weight) and BHA (0.25 mg/kg). Rats excrete about 10% of an oral dose of 200 mg BHT/kg as unchanged BHT in the faeces, whereas in man no BHT could be detected in the faeces. Urinary excretion of (un)conjugated 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) accounts for only a small percentage of the administered dose in both rats and humans. It is concluded that the plasma BHT concentrations reached after the administration of a single medium to high dose of BHT to rats or a single low dose to man are very different.
authors.affiliation: Department of Human Biology, University of Limburg, Maastricht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Verhagen
authors.forename: H H
authors.initials: HH
authors.lastname: Beckers
authors.forename: P A
authors.initials: PA
authors.lastname: Comuth
authors.forename: L M
authors.initials: LM
authors.lastname: Maas
authors.forename: F
authors.initials: F
authors.lastname: ten Hoor
authors.forename: P T
authors.initials: PT
authors.lastname: Henderson
authors.forename: J C
authors.initials: JC
authors.lastname: Kleinjans
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001711:Biotransformation; D002083:Butylated Hydroxyanisole / Q000493:pharmacokinetics; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D010226:Parabens / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010226:Parabens; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; C062323:3,5-di-tert-butyl-4-hydroxybenzoic acid