TOXICOKINETICS OF PENTACHLOROPHENOL IN THE F344 RAT - GAVAGE AND DOSED FEED STUDIES

1. The toxicokinetics of pentachlorophenol (PCP) were studied in the F ischer 344 rat using i.v. and oral (gavage, dosed feed) routes of expo sure. 2. Only minor sex differences were observed in the elimination k inetics of PCP after i.v. administration at 5 mg/kg. 3. Absorption of PCP from the gastrointestinal tract after gavage doses of 9.5 and 38 m g/kg in aqueous methylcellulose vehicles was first order with an absor ption half-life of about 1.3 h. 4. The absorption rate constant of PCP from doses feed was comparable with that obtained from aqueous methyl cellulose gavage formulations. 5. Bioavailability of PCP administered in dosed feed was significantly lower than the bioavailability of PCP administered by gavage. 6. Dose proportionality was established to a d osage of at least 38 mg/kg. 7. Daily fluctuation of PCP plasma concent rations was observed during the dosed feed study with peak and trough concentrations occurring in early morning and late afternoon, respecti vely. 8. The time course of PCP plasma concentrations during the dosed feed study were simulated using a computer model based on linear theo ry. The simulations were comparable with the experimentally determined concentrations.