A toxicokinetic study to elucidate 3-hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats.
The toxicokinetics of benzo(a)pyrene (BaP) and 3-hydroxybenzo(a)pyrene (3-OHBaP) were assessed in 36 male Sprague-Dawley rats injected intravenously with 40 micromol kg(1) of BaP to explain the reported atypical urinary excretion profile of 3-OHBaP. Blood, liver, kidney, lung, adipose tissue, skin, urine and feces were collected at t = 2, 4, 8, 16, 24, 33, 48, 72 h post-dosing. BaP and 3-OHBaP were measured by high-performance liquid chromatography/fluorescence. A biexponential elimination of BaP was observed in blood, liver, skin and kidney (t((1/2)) of 4.2-6.1 h and 12.3-14.9 h for initial and terminal phases, respectively), while a monoexponential elimination was found in adipose tissue and lung (t((1/2)) of 31.2 and 31.5 h, respectively). A biexponential elimination of 3-OHBaP was apparent in blood, liver and skin (t((1/2)) of 7.3-11.7 h and 15.6-17.8 h for initial and terminal phases, respectively), contrary to adipose tissue, lung and kidney. In adipose tissue and lung, a monophasic elimination of 3-OHBaP was observed (t((1/2)) of 27.0 h and 24.1 h, respectively). In kidney, 3-OHBaP kinetics showed a distinct pattern with an initial buildup during the first 8 h post-dosing followed by a gradual elimination (t((1/2)) of 15.6 h). In the 72-h post-treatment, 0.21 +/- 0.09% (mean +/- SD) of dose was excreted as 3-OHBaP in urine and 12.9 +/- 1.0% in feces while total BaP in feces represented 0.40 +/- 0.16% of dose. This study allowed the identification of the kidney as a retention compartment governing 3-OHBaP atypical urinary excretion.
Marie
Caroline
C
Department of Environmental and Occupational Health, Université de Montréal, Main Station, Montreal, Quebec, Canada. michele.bouchard@umontreal.ca
Bouchard
Michèle
M
Heredia-Ortiz
Roberto
R
Viau
Claude
C
Maître
Anne
A
D000818:Animals; D019540:Area Under Curve; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics* / Q000633:toxicity; D001580:Benzopyrenes / Q000032:analysis / Q000378:metabolism*; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001580:Benzopyrenes; D002273:Carcinogens; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene