URINARY-EXCRETION KINETICS OF 1-HYDROXYPYRENE IN VOLUNTEERS EXPOSED TO PYRENE BY THE ORAL AND DERMAL ROUTE

Two well-informed human volunteers were exposed to 500 mu g pyrene by ingestion and by dermal application, in two separate experiments. Urinary measurements of 1-hydroxypyrene (1-OHP) were performed on all micturitions taken at intervals of 0.5-4 h for a total period of 48 h after dosing. Following the absorption phase, 1-OHP is excreted with a first order apparent half-life of approximately 12 h for both volunteers and both exposure routes. These results compare well with other previously published studies. A more refined analysis of the data was performed using a two-compartment toxicokinetic model for 'pyrene' (its fraction eventually excreted as 1-OHP). As it was found that a classical first-order system did not adequately fit the data, a non-linear term was introduced in the model for the elimination of urinary 1-OHP. Computer iteration performed on the oral absorption data allowed an estimation of various toxicokinetic parameter values. The mean intercompartmental exchange (k(12) and k(21)) and elimination coefficients were 0.010, 0.006 and 0.012 min(-1), respectively. The first two values compare well with those previously published for the rat, whereas the latter is smaller in humans. These values were used to satisfactorily simulate the experimental data for both routes of exposure, adjusting only for k(abs) which was estimated at 0.014 and 0.0029 min(-1) for the oral and dermal exposure, respectively. The proposed model generates new hypotheses on the metabolism of pyrene. The information collected will contribute to the validation of the utilisation of 1-OHP as a biological indicator of exposure to pyrene.