Toxicokinetics of p-tert-octylphenol in female DA/Han rats after single i.v. and oral application

Female DA/Han rats were administered p-tert-octylphenol [OP; p-(1,1,3,3-tet ramethylbutyl)-phenol], either intravenously (5 mg/kg body wt.) or orally b y gavage (50 or 200 mg/kg body wt.). After i.v. administration the blood co ncentration-time curve of OP was fitted to a tri-exponential model, resulti ng in a final half-life (gamma-phase) of 36.1 h. This contrasts to much mor e rapid eliminations previously reported in male Wistar rats. The oral bioa vailability of 50 mg/kg OP was 12.3% and of 200 mg/kg 8.4%. The higher dose (200 mg/kg) was absorbed slower than the smaller dose, probably due to low solubility of OP in aqueous media. Maximal OP blood levels in female DA/Ha n rats receiving 50 and 200 mg OP/kg body wt. were 4.5 and 3 times higher t han previously reported in male Wistar rats. The blood concentration-time c urves after oral administration of OP to female DA/Han rats revealed pronou nced interindividual differences, indicating extensive enterohepatic circul ation of OP in this rat strain. In contrast to male Wistar rats, after appl ication of high doses of OP to female DA/Han rats the compound was not comp letely eliminated within 48 h; under these conditions some bioaccumulation might therefore occur. The experimental toxicokinetics of OP appears as a r elevant subject to be integrated into extrapolation of toxicological data, from in vitro to in vivo, and into systems of risk assessment of endocrine modulating activity which are currently being developed.