Département de Santé Environnementale et Santé au Travail and Institut de Recherche en Santé Publique de l'Université de Montréal (IRSPUM), Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3C3J7.
Toxicol Sci. 2011 Aug;122(2):275-87. doi: 10.1093/toxsci/kfr135. Epub 2011 May 24.
Measurements of 3-hydroxybenzo(a)pyrene (3-OHBaP) in urine has been proposed for the biomonitoring of exposure to benzo(a)pyrene (BaP) in workers. To allow a better understanding of the toxicokinetics of BaP and its key biomarker, a multicompartment model was developed based on rat data previously obtained by this group. According to the model, iv injected BaP is rapidly distributed from blood to tissues (t₁/₂ = 3.65 h), with particular affinity for tissue lipid components and liver and lung proteins. BaP is then rapidly distributed to lungs, where significant tissue uptake occurs, followed by the skin, liver, and adipose tissues. Once in liver, BaP is readily metabolized, and 3-OHBaP is formed with a t₁/₂ of 3.32 h. Lung metabolism of BaP was also accounted for, but its contribution to the whole kinetics was found to be negligible. Once formed, 3-OHBaP is distributed from blood to the various organs almost as fast as the parent compound (t₁/₂ = 2.26 h). In kidneys, 3-OHBaP builds up as a result of the smaller rate of 3-OHBaP urinary excretion (t₁/₂ = 4.52 h) as compared with its transfer rate from blood to kidneys (t₁/₂ = 27.8 min). However, overall clearance of 3-OHBaP from the body is driven by its biliary transfer from liver to the gastrointestinal tract (t₁/₂ = 3.81 h). The model provides a great fit to independent sets of published data on 3-OHBaP urinary excretion time course (χ² = 0.019). This model proves useful in establishing the main biological determinants of the overall kinetics of these compounds.
尿液中 3-羟基苯并(a)芘（3-OHBaP）的测量已被提议用于监测工人接触苯并(a)芘（BaP）的情况。为了更好地了解 BaP 及其关键生物标志物的毒代动力学，本研究组基于之前获得的大鼠数据，建立了一个多室模型。根据该模型，静脉注射的 BaP 迅速从血液分布到组织（t₁/₂=3.65 小时），对组织脂质成分和肝脏及肺蛋白具有特殊亲和力。然后，BaP 迅速分布到肺部，在肺部发生显著的组织摄取，随后是皮肤、肝脏和脂肪组织。进入肝脏后，BaP 很容易被代谢，形成 3-OHBaP，其 t₁/₂为 3.32 小时。还考虑了 BaP 在肺部的代谢，但发现其对整个动力学的贡献可以忽略不计。一旦形成，3-OHBaP 从血液分布到各个器官的速度几乎与母体化合物一样快（t₁/₂=2.26 小时）。在肾脏中，由于 3-OHBaP 从血液向肾脏的转移速率（t₁/₂=27.8 分钟）与 3-OHBaP 尿排泄率（t₁/₂=4.52 小时）相比较小，3-OHBaP 会在肾脏中蓄积。然而，3-OHBaP 从体内的总体清除率是由其从肝脏到胃肠道的胆汁转移驱动的（t₁/₂=3.81 小时）。该模型与 3-OHBaP 尿排泄时间过程的独立发表数据集拟合良好（χ²=0.019）。该模型在确定这些化合物整体动力学的主要生物学决定因素方面非常有用。
