Urinary excretion kinetics of 1-hydroxypyrene in rats subchronically exposed to pyrene or polycyclic aromatic hydrocarbon mixtures

Abstract

The urinary excretion kinetics of 1-hydroxypyrene (1-OHP) were studied in male Sprague-Dawley rats exposed orally, on Tuesdays and Fridays for 10 consecutive weeks, to 0.046 mg/kg/d of pyrene or 0.3, 1 or 3 mg/kg/d of polycyclic aromatic hydrocarbon (PAH) mixtures containing pyrene (0.046, 0.15, and 0.46 mg/kg/d, respectively). During the subchronic exposure, 24-h urine samples were collected on Mondays (prior to exposure) and Tuesdays (after exposure) for all exposure groups. During a 14-d period following last exposure in rats treated with 3 mg/kg/d of PAH mixture, 24-h urine samples were collected at frequent time intervals (0-24, 48-72, 96-120, 144-168, 193-217, 313-338 h). Whatever the administered dose, repeated exposures to pyrene and PAH mixtures resulted in a progressive time-dependent increase in the daily urinary excretion of 1-OHP. After 10 wk of treatment, daily excretion rates were on average 5 times higher than those observed after the first administration. Following the subchronic exposure to 3 mg/kg/d of PAH mixture, the time profile of 1-OHP excretion in rat urine showed a multiphasic elimination. An average first-order apparent elimination half-life of 26.5 h could be estimated for the 48-168 h period following the end of the exposure. The observed time-dependent increase in 1-OHP excretion values upon repeated exposures to PAHs does not appear to result from a PAH enzyme induction effect of pyrene metabolism to 1-OHP. Rather, the slow release of residual pyrene accumulated in a long-term compartment and/or the enterohepatic recirculation of 1-OHP and other pyrene metabolites may play significant roles in the observed urinary excretion kinetics of 1-OHP. Furthermore, the absence of mixture effect on the urinary excretion of 1-OHP suggests that 1-OHP is a good bioindicator of exposure to complex PAH mixtures, in the dose range used in this study.