Toxicokinetics of pentachlorophenol in the F344 rat. Gavage and dosed feed studies

Abstract

1. The toxicokinetics of pentachlorophenol (PCP) were studied in the Fischer 344 rat using i.v. and oral (gavage, dosed feed) routes of exposure.

2. Only minor sex differences were observed in the elimination kinetics 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 mg/kg in aqueous methylcellulose vehicles was first order with an absorption half-life of about 1.3 h.

4. The absorption rate constant of PCP from doses feed was comparable with that obtained from aqueous methylcellulose 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 dosage of at least 38 mg/kg.

7. Daily fluctuation of PCP plasma concentrations was observed during the dosed feed study with peak and trough concentrations occurring in early morning and late afternoon, respectively.

8. The time course of PCP plasma concentrations during the dosed feed study were simulated using a computer model based on linear theory. The simulations were comparable with the experimentally determined concentrations.