Sun J D, Wolff R K, Kanapilly G M, McClellan R O
Toxicol Appl Pharmacol. 1984 Mar 30;73(1):48-59. doi: 10.1016/0041-008x(84)90052-8.
Polycyclic aromatic hydrocarbons (PAHs) are a class of compounds considered to have human carcinogenic potential and have been found associated with many respirable, environmental particle pollutants. The effect of these ultrafine, insoluble, carrier particles on the lung retention and metabolic fate of inhaled PAHs was investigated with a radiolabeled model PAH, [3H]benzo(a)pyrene (3H-BaP). Fischer-344 rats were exposed (30 min) by nose-only inhalation to 3H-BaP adsorbed (approximately 0.1% by mass) onto diesel engine exhaust particles. These aerosols were generated in a dynamic aerosol generation system by vapor condensation methods. The total mass concentration of these aerosols was 4-6 micrograms/liter of air with a mass median diameter of 0.14 micron. Lung clearance of the inhaled particle-associated 3H radioactivity occurred in two phases. The initially rapid clearance of this inhaled radiolabel had a half-time of less than 1 hr. The second, long-term component of lung clearance had a half-time of 18 +/- 2 days and represented 50 +/- 2% of the 3H radioactivity that had initially deposited in lungs. In contrast, previous inhalation studies with a pure 3H-BaP aerosol showed that greater than 99% of the 3H radioactivity deposited in lungs was cleared within 2 hr after exposure (Sun et al., Toxicol. Appl. Pharmacol. 65, 231-244, 1982). By HPLC analysis, the majority of diesel soot-associated 3H radioactivity retained in lungs was BaP (65-76%) with smaller amounts of BaP-phenol (13-17%) and BaP-quinone (5-18%) metabolites also being detected. No other metabolites of BaP were detected in lungs of exposed rats. Tissue distribution and excretion patterns of 3H radioactivity were qualitatively similar to previous inhalation studies with 3H-BaP coated Ga2O3 aerosols (Sun et al., 1982). These findings suggest that inhaled PAHs may be retained in lungs for a greater period of time when these compounds are associated with diesel engine exhaust particles. In addition, these compounds retained in lungs can be metabolized in lungs. These results may have significant implications for the health risks that may be involved with human exposure to particle-associated organic pollutants.
多环芳烃(PAHs)是一类被认为具有人类致癌潜力的化合物,并且已发现其与许多可吸入的环境颗粒污染物有关。使用放射性标记的模型多环芳烃[³H]苯并(a)芘(³H-BaP)研究了这些超细、不溶性载体颗粒对吸入多环芳烃在肺部的滞留及代谢命运的影响。通过仅经鼻吸入,将吸附在柴油机排气颗粒上(质量分数约0.1%)的³H-BaP暴露于Fischer-344大鼠30分钟。这些气溶胶通过蒸汽冷凝法在动态气溶胶生成系统中产生。这些气溶胶的总质量浓度为4 - 6微克/升空气,质量中值直径为0.14微米。吸入的与颗粒相关的³H放射性在肺部的清除分为两个阶段。最初快速清除这种吸入的放射性标记物的半衰期小于1小时。肺部清除的第二个长期成分的半衰期为18±2天,占最初沉积在肺部的³H放射性的50±2%。相比之下,先前对纯³H-BaP气溶胶的吸入研究表明,暴露后2小时内,沉积在肺部的³H放射性中有超过99%被清除(Sun等人,《毒理学与应用药理学》65卷,231 - 244页,1982年)。通过高效液相色谱分析,肺部保留的与柴油机烟灰相关的³H放射性中,大部分是BaP(65 - 76%),还检测到少量的BaP - 酚(13 - 17%)和BaP - 醌(5 - 18%)代谢物。在暴露大鼠的肺部未检测到BaP的其他代谢物。³H放射性的组织分布和排泄模式在质量上与先前对涂有³H-BaP的Ga₂O₃气溶胶的吸入研究相似(Sun等人,1982年)。这些发现表明,当这些化合物与柴油机排气颗粒相关时,吸入的多环芳烃可能在肺部保留更长时间。此外,保留在肺部的这些化合物可在肺部代谢。这些结果可能对人类接触与颗粒相关的有机污染物所涉及的健康风险具有重要意义。