Urinary excretion of benzo[a]pyrene metabolites following intravenous, oral, and cutaneous benzo[a]pyrene administration.
The effect of the administration route, dose, and sampling time on the total urinary excretion of four major benzo[a]pyrene (BaP) metabolites, 3-hydroxyBaP (3-OHBaP), 9-hydroxyBaP 9-hydroxyBaP (9-OHBaP), trans-4,5-dihydrodiolBaP (4,5-diolBaP), and trans-9,10-dihydrodiolBaP (9,10-diolBaP), was studied in male Sprague-Dawley rats exposed to a single intravenous, oral, and cutaneous dose of 2, 6, 20, and 60 mumol BaP/kg. Urine samples were collected at 24-h intervals following treatment. Over the 0-72 h period and for a given dose, amounts of BaP metabolites were 3-OHBaP > 4,5-diolBaP > > 9-OHBaP following intravenous and oral dosing, and 3-OHBaP > > 9-OHBaP > or = 4,5-diolBaP after cutaneous treatment. 9,10-diolBaP was barely detected. On the other hand, amounts of 3-OHBaP and 4,5-diolBaP excreted in urine over the 0-72 h period and for a given dose appeared in the following order: intravenous approximately oral > or = cutaneous. Amounts of 9-OHBaP excreted varied as follows: oral > or = cutaneous > intravenous. For all routes of administration, excretion of 4,5-diolBaP was almost complete over the 0-24 h period in contrast with 3-OHBaP and 9-OHBaP. Peak excretion of 3-OHBaP and 9-OHBaP was reached in the 0-24 h period following intravenous and oral treatment and in the 24-48 h period following cutaneous application. Overall, for a given administration route and dose, there were variations in the time profiles between metabolites. In general, there was nonetheless a good correlation between the BaP dose and urinary excretion of 3-OHBaP, 9-OHBaP, and 4,5-diolBaP. Furthermore, total urinary excretion of a specific metabolite, its time profile, and the relative proportion of the metabolites studied depended on the administration route. Data also suggest that a measure of the concentration ratio of the different metabolites could reflect the time and main route of exposure.
Bouchard
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M
Départment de médecine du travail et d'hygiène du milieu, Université de Montréal, QC, Canada.
Viau
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D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D001580:Benzopyrenes / Q000032:analysis; D004101:Dihydroxydihydrobenzopyrenes / Q000652:urine; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; D004785:Environmental Pollutants; C021337:9-hydroxybenzo(a)pyrene; C015813:4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene