Department of Environmental and Occupational Health, Université de Montréal, Main Station, Montreal, Quebec, Canada.
J Appl Toxicol. 2010 Jul;30(5):402-10. doi: 10.1002/jat.1511.
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.
苯并(a)芘（BaP）和 3-羟基苯并(a)芘（3-OHBaP）的毒代动力学在 36 只雄性 Sprague-Dawley 大鼠中进行评估，这些大鼠静脉注射 40 微摩尔/千克的 BaP，以解释报告的 3-OHBaP 非典型尿排泄模式。在给药后 2、4、8、16、24、33、48 和 72 小时收集血液、肝脏、肾脏、肺、脂肪组织、皮肤、尿液和粪便。通过高效液相色谱/荧光法测定 BaP 和 3-OHBaP。在血液、肝脏、皮肤和肾脏中观察到 BaP 的双指数消除（初始和终末相的 t((1/2))分别为 4.2-6.1 h 和 12.3-14.9 h），而在脂肪组织和肺中观察到单指数消除（t((1/2))分别为 31.2 和 31.5 h）。在血液、肝脏和皮肤中，3-OHBaP 的双指数消除明显（初始和终末相的 t((1/2))分别为 7.3-11.7 h 和 15.6-17.8 h），而脂肪组织、肺和肾脏则不然。在脂肪组织和肺中，观察到 3-OHBaP 的单相消除（t((1/2))分别为 27.0 h 和 24.1 h）。在肾脏中，3-OHBaP 的动力学表现出明显的模式，即在给药后 8 小时内初始积累，然后逐渐消除（t((1/2))为 15.6 h）。在治疗后 72 小时，尿液中以 3-OHBaP 形式排泄的剂量为 0.21 +/- 0.09%（平均值 +/- SD），粪便中排泄的剂量为 12.9 +/- 1.0%，而粪便中总 BaP 占剂量的 0.40 +/- 0.16%。这项研究确定了肾脏作为控制 3-OHBaP 非典型尿排泄的保留部位。
