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 intravenous administration of pyrene and BaP, respectively, or after injection of the metabolites themselves. Male Sprague-Dawley rats were exposed to 4 mumol 1-OHP/kg or 15 mumol pyrene/kg. Other rats were exposed to 2 mumol/kg of a mixture of four BaP metabolites (3-hydroxyBaP (3-OHBaP), 9-hydroxyBaP (9-OHBaP), trans-4,5-dihydrodiolBaP (4,5-diolBaP), and trans-9,10-dihydrodiol (9,10-diolBaP)) or 40 mumol BaP/kg. Urine samples were collected at frequent intervals over 48 or 96 hr. Injection of both pyrene and 1-OHP produced similar biphasic excretion profiles. 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 mixture of BaP metabolites. Elimination kinetics showed at least two steps, the second step having a first order apparent half life of 8.1 and 7.6 hr following BaP and BaP metabolites injection, respectively. Time profiles of 4,5-diolBaP excretion following administration of BaP or 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 suggest 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 injection of pyrene and BaP, respectively and (2) similarities in the first 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.
Bouchard
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M
Départment de médecine du travail et d'hygiène du milieu, Université de Montréal, Canada.
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D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D004101:Dihydroxydihydrobenzopyrenes / Q000652:urine; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000378:metabolism*; D011721:Pyrenes / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine / Q000737:chemistry*
D001580:Benzopyrenes; D002273:Carcinogens; D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; D011721:Pyrenes; C021337:9-hydroxybenzo(a)pyrene; C020738:9,10-dihydro-9,10-dihydroxybenzo(a)pyrene; C015813:4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene; C033146:1-hydroxypyrene