Bioavailability and Metabolism of Hydroquinone after Intratracheal Instillation in Male Rats
AbstractAbstract The purpose of this study was to investigate the rate and extent of hydroquinone (HQ) absorption and first pass metabolism in the lungs of male rats in vivo. 14 CHQ in physiological saline was administered intratracheally via an indwelling endotracheal tube to simulate inhalation exposure to HQ dust. The bioavailability of HQ was determined by blood sampling simultaneously at arterial and venous sites beginning immediately after administration to conscious rats. Pulmonary absorption and metabolism, and systemic metabolism and elimination were determined by chromatographic analysis of parent compound and metabolites in blood samples after intratracheal administration of 14 CHQ at 0.1, 1.0, and 10 mg/kg. Pulmonary absorption of HQ was found to be very rapid with 14 CHQ detectable in arterial blood, and to a lesser extent in venous blood, within 5 to 10 s after dose administration. Only 14 CHQ was detected in the initial (5–10 s) arterial blood samples at all dose levels, indicating that pulmonary metabolism of HQ was not extensive. However, later blood samples (45–720 s) indicated rapid metabolism and elimination of the parent compound and metabolites after intratracheal absorption. The elimination half-life from the 0.1 mg/kg dose was allometrically scaled to human proportions and used to estimate the steady-state (maximum) human blood concentrations of HQ resulting from presupposed workplace exposures. The estimates indicated minimal levels of HQ in human blood after respiratory exposures of greater than 1 h at 0.1 or 2.0 mg/m 3 ; these levels were less than background concentrations of HQ detected in human blood in previous studies.