URINARY-EXCRETION KINETICS OF PYRENE AND BENZO(A)PYRENE METABOLITES FOLLOWING INTRAVENOUS ADMINISTRATION OF THE PARENT COMPOUNDS OR THE METABOLITES

The detailed urinary excretion profiles of 1-hydroxypyrene (1-OHP) and benzo(a)pyrene (BaP) metabolites were studied following acute intrave nous administration of pyrene and BaP, respectively, or after injectio n of the metabolites themselves. Male Sprague-Dawley rats were exposed to 4 mu mol 1-OHP/kg or 15 mu mol pyrene/kg. Other rats were exposed to 2 mu mol/kg of a mixture of four BaP metabolites (3-hydroxyBaP (3-O HBaP), 9-hydroxyBaP (9-OHBaP), trans-4,5-dihydrodiolBaP (4,5-diolBaP), and trans-9,10-dihydrodiol (9,10-diolBaP)) or 40 mu mol BaP/kg. Urine samples were collected at frequent intervals over 48 or 96 hr. Inject ion of both pyrene and 1-OHP produced similar biphasic excretion profi les. An apparent first order half life of 6.9 and 6.6 hr, respectively , could be calculated for the second phase of elimination. Comparable 3-OHBaP excretion profiles were obtained after injection of BaP or a m ixture of BaP metabolites, Elimination kinetics showed at least two st eps, the second step having a first order apparent half life of 8.1 an d 7.6 hr following BaP and BaP metabolites injection, respectively. Ti me profiles of 4,5-diolBaP excretion following administration of BaP o r a mixture of BaP metabolites were almost identical. Elimination was linear and a first order apparent half life of 3.1 and 3.6 hr could be calculated, Elimination of 4,5-diolBaP was much more rapid than that of 3-OHBaP and complete within 24 hr postdosing. Therefore, results su ggest that (1) phase I biotransformation is not the rate-limiting step in the excretion of 1-OHP, and 3-OHBaP and 4,5-diolBaP following inje ction of pyrene and BaP, respectively, and (2) similarities in the fir st order apparent half life of 3-OHBaP and 1-OHP for the late phase of excretion suggest that 1-OHP could be a good surrogate for 3-OHBaP. ( C) 1996 Academic Press, Inc.