Urinary excretion kinetics of 1-hydroxypyrene following intravenous administration of binary and ternary mixtures of polycyclic aromatic hydrocarbons in rat

Abstract

The effect of exposure to binary and ternary mixtures of polycyclic aromatic hydrocarbons (PAHs) on the urinary excretion kinetics of 1-hydroxypyrene (1-OHP) has been examined. Male Sprague-Dawley rats were administered intravenously 5 μ mol/kg of pyrene alone or in combination with 0.5, 5 and 25 μ mol/kg of either naphthalene, benzo(a)pyrene (BaP), or both. Urine samples were collected at frequent intervals over 48 h. The kinetics of 1-OHP in urine was not altered by the presence of either naphthalene or BaP in the mixtures, at least from 4 h post-dosing. Hence, none of the injected mixtures significantly modified the first-order apparent elimination half-life of 1-OHP in urine obtained for the 12 to 42 h period post injection where mean values ranged between 6.2 and 9.6 h. However, while the presence of naphthalene or the low BaP dose of 0.5 μ mol/kg in the mixtures did not have a significant effect on the total excretion of 1-OHP, BaP doses of 5 and 25 μ mol/kg in the mixtures significantly increased the amount of 1-OHP excreted in urine. Mean percentages of the pyrene dose excreted as 1-OHP after injection of pyrene in combination with 0.5, 5 and 25 μmol/kg BaP were respectively increased 1.3, 2.2 and 2.6 times compared to the value obtained after administration of pyrene alone. The percentages determined after concomitant administration of pyrene and 0.5, 5 and 25 μ mol/kg of BaP plus naphthalene were 1.4, 1.8 and 2.4 times, respectively, the value obtained after administration of pyrene singly. The observed effect of BaP (5 or 25 μ mol/kg) on 1-OHP total excretion appears to result from BaP induction of pyrene metabolism. Lack of effect of naphthalene appears to be due to its weak P450 1A1 enzyme induction capacity. Absence of significant effect of the low BaP dose in the mixtures (0.5 μ mol/kg) suggests that 1-OHP in urine is useful as a bioindicator of occupational and environmental exposures to PAH mixtures.