Medinsky M A, Kampcik S J
Toxicology. 1985 Jun 28;35(4):327-36. doi: 10.1016/0300-483x(85)90066-6.
Studies on the pulmonary retention of benzo[a]pyrene after inhalation have shown that clearance is biphasic, with one component clearing with a half-time greater than 1 day and another with a half-time less than 1 day. In the work reported here we demonstrated that the amount of benzo[a]pyrene instilled in the lungs can affect the rate at which the benzo[a]pyrene is cleared into the blood. Fischer-344 rats were given 16, 90 or 6400 ng of [14C]benzo[a]-pyrene/rat by intratracheal instillation. Rats were sacrificed at various times up to 7 days after instillation. Individual lung lobes and trachea were removed, digested, and analyzed by liquid scintillation spectrometry. At 24 h after instillation the amount of 14C covalently bound to lung macromolecules was determined in some rats. Benzo[a]pyrene equivalents remaining in the lungs was expressed as a percentage of the instilled dose as a function of time. A two-component negative exponential function was fit to the data. With increasing dose (16-6400 ng/rat), an increasing percent (89-99.76%) was cleared with a half-time less than 1 day and a decreasing percent (11.3-0.24%) was cleared with a half-time greater than 1 day, suggesting that the mechanism by which the slower clearances occurred had been saturated at higher doses. At 24 h after instillation, from 1 to 2 pmol of [14C]benzo[a]-pyrene equivalents/lung were covalently bound to lung macromolecules. There was no difference in the amount of covalently bound 14C over the range of instillation doses used, suggesting that a small amount of benzo[a]-pyrene equivalents was bound in the lungs regardless of the amount instilled. These results suggested that linear extrapolation from high dose studies to environmental concentrations might underestimate lung burdens of benzo[a]pyrene.
吸入苯并[a]芘后肺部滞留情况的研究表明，清除过程呈双相性，其中一个成分的清除半衰期大于1天，另一个成分的清除半衰期小于1天。在本文报道的研究中，我们证明了注入肺部的苯并[a]芘量会影响其清除进入血液的速率。通过气管内注入法给Fischer - 344大鼠每只注入16、90或6400纳克[14C]苯并[a]芘。在注入后长达7天的不同时间点处死大鼠。取出各个肺叶和气管，进行消化，并通过液体闪烁光谱法进行分析。在注入后24小时，测定了部分大鼠中与肺大分子共价结合的14C量。肺部残留的苯并[a]芘当量表示为注入剂量的百分比随时间的函数。对数据拟合了双成分负指数函数。随着剂量增加（16 - 6400纳克/只），清除半衰期小于1天的百分比增加（89 - 99.76%），清除半衰期大于1天的百分比降低（11.3 - 0.24%），这表明在较高剂量下，较慢清除发生的机制已达到饱和。注入后24小时，每肺有1至2皮摩尔的[14C]苯并[a]芘当量与肺大分子共价结合。在所使用的注入剂量范围内，共价结合的14C量没有差异，这表明无论注入量多少，肺部都会结合少量的苯并[a]芘当量。这些结果表明，从高剂量研究线性外推至环境浓度可能会低估苯并[a]芘的肺部负担。
