Benzo(a)pyrenediolepoxide-hemoglobin adducts and 3-hydroxy-benzo(a)pyrene urinary excretion profiles in rats subchronically exposed to benzo(a)pyrene

 The time profiles of benzo(a)pyrenediolepoxide (BaPDE)-hemoglobin (Hb) adduct formation and 3-hydroxybenzo(a)pyrene (3-OHBaP) urinary excretion were studied in male Sprague-Dawley rats exposed to daily benzo(a)pyrene (BaP) intraperitoneal doses of 1.25, 6.25, and 31.25 μmol/kg administered Tuesday to Friday for 4 consecutive weeks. Blood was withdrawn weekly, on Tuesdays, prior to dosing. Twenty four hour urine samples were collected on Mondays (following 72 h without treatment) and Thursdays. Analytes were quantified by high performance liquid chromatography (HPLC)/fluorescence. Exposure to BaP resulted in the accumulation of BaPDE-Hb adducts, reaching an average of 1.2±0.3, 8.3±1.9, and 38.2±6.1 pmol/g Hb for the 1.25, 6.25, and 31.25 μmol/kg per day doses after 4 weeks of treatment. The expected saw tooth excretion profile of 3-OHBaP was observed, with peaks on Thursdays and troughs on Mondays, and showed a progressive rise on both Mondays and Thursdays. Increase in Monday values with time suggested a possible increase in BaP body burden during exposure. To verify this aspect further, the urinary excretion kinetic of 3-OHBaP following acute intraperitoneal dosing (31.25 μmol/kg) was determined. Urine samples were collected at frequent timed intervals for up to 164 h post-dosing. Two-step elimination was observed, the second step having a half-life of 25 h, presumably linked to the slow release of BaP accumulated in fatty tissues upon repeated treatment. Therefore, it seems that 1) BaPDE-Hb adducts are good indicators of repeated exposure, 2) the difference between pre- and post-exposure 3-OHBaP urinary excretion gives a measure of recent exposure, and 3) excretion levels of this latter metabolite after a non-exposure period of sufficient duration, to allow elimination of the bulk BaP from the last dose, could reflect BaP body burden. Received: 3 November 1994/Accepted: 11 January 1995