Pentachlorophenol toxicokinetics after intravenous and oral administration to rat

Abstract

1. The toxicokinetics of pentachlorophenol (PCP) were studied in rats. Doses of 2˙5 mg/kg were given i.v. (bolus, five rats) and orally (gastric intubation, five rats). Concentrations in plasma, urine and faeces were measured by capillary g.l.c. with electroncapture detection.

2. After i.v. administration, the clearance and volume of distribution at steady state were 0˙026±0˙0031/h per kg and 0˙25±0˙021/kg, respectively. These two parameters exhibit low inter-rat variability (coefficients of variation <15%). The half-life of the initial decline of PCP plasma concn. was less than 1˙3 h, while the second phase half-life was 7˙11 ±0˙87 h.

3. After oral administration the peak plasma concn. (7˙3±2˙8 ug/ml) occurred between 1˙5 and 2h and absorption was complete (bioavailability = 0˙91-0˙97). No distinct distribution phase was observed and the elimination half-life was 7˙54±0˙44 h.

4. PCP clearance is essentially metabolic since only 5˙3±0˙2% dose is eliminated unchanged by the kidney. About 60% dose was recovered in urine, mainly as conjugated PCP and conjugated tetrachlorohydroquinone (TCHQ).

5. For both routes of administration, about 10% dose was recovered in faeces as PCP and/or metabolites, which indicates that biliary excretion contributes to total elimination.