Metabolism and disposition of hydroquinone in Fischer 344 rats after oral or dermal administration

Studies were conducted to determine the absorption, tissue distribution, excretion, and metabolism of C-14-hydroquinone (HQ) in male and female rats following single oral, repeated oral, or 24-h dermal administration. The concentration of parent compound in blood was also determined following a single 50-mg/kg gavage administration. Absorption into the blood was rapid after oral dosing; the maximum concentration of parent compound was attained within 20 min after dosing, and the maximum concentration of total C-14 was attained within 30 min. Parent compound represented less than or equal to1% of total C-14 in blood, indicative of extensive first-pass metabolism. Excretion was primarily via the urine within the first 8 h of gavage. Typically, 87-94% of the C-14 was excreted in urine. Dermal application of C-14-HQ (20 muCi) as a 5.4% aqueous solution resulted in near background levels of C-14 in blood; the maximum mean blood concentration was 0.65 mug HQ equivalents/g in females and not quantifiable in males. The majority (61-71%) of the C-14 was recovered from the skin surface by washing at 24 h. HQ was extensively metabolized following oral dosing with typically <3% of the dose excreted as parent compound. The major urinary metabolites of HQ were glucuronide and O-sulfate conjugates, which represented 45-53% and 19-33%, respectively, of an oral dose. A <5% metabolite was identified as a mercapturic acid conjugate of HQ (C) 2004 Elsevier Ltd. All rights reserved.