Persistence of benzo[a]pyrene and 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene in Fischer 344 rats: time distribution of total metabolites in blood, urine and feces

A comparison of the rates of elimination of ³H]benzoa] pyrene(BaP) and 7,8-dihydro-7,8-diol-³H]benzoa]pyrene (BPD), aftersubcutaneous injection into Fischer 344 rats, shows they areboth eliminated at about the same rates and with the same patternover at least 7 days post-exposure. The end-rate of combinedurinary and fecal excretion was {small tilde}40 nmol/day. About20% of the injected BaP and {small tilde}3% of the injectedBPD remained at the site of injection for at least 9 days. Theremainder was distributed throughout the animal. If the rateof excretion continued at the observed steady-state rates, theBaP and BPD could persist for up to 40 days for each milligramof injected substance. The concentration of excretion productswere highest during day 1 and day 2 following exposure, decreasedexponentially to a concentration of {small tilde}0.5 µM(mixed metabolites) by day 5 following exposure, and then continuedto be excreted at that rate. Feces contained the highest totalamounts of radioactivity, which were {small tilde}2- to 4-foldhigher than the amounts in urine and {small tilde}15- to 50-foldhigher than in total blood. The conversion of organic ³H to³H₂O during the experimental period indicates.that whole-bodyphenol(quinone) formation was significant for BaP metabolism,but was much less for BPD metabolism. When BaP was injected,both blood and urine contained water-soluble, volatile tritiumcounts (³H₂O). Injection of BPD resulted in volatile ³H₂O inurine but not in blood. The persistence of BaP and BPD metabolitesin skin, blood, urine and feces compartments indicates thereis a substantial reservoir of the chemical(s) that could beused to replenish repaired or discarded DNA adducts.