Bond J A, Baker S M, Bechtold W E
Toxicology. 1985 Sep;36(4):285-95. doi: 10.1016/0300-483x(85)90031-9.
Studies on the lung retention of polycyclic aromatic hydrocarbons (PAH) after inhalation have indicated that, in general, the PAH are rapidly cleared from the respiratory tract. Clearance of the PAH from the lungs is best described as bi-phasic, with the long-term component of the clearance curve having a half-time of greater than 24 h. The purpose of this study was to determine whether a relationship exists between the lipophilicity (as measured by the octanol/water partition coefficient, P) of various PAH and the short-term and long-term clearance half-times of PAH in rat lungs. Female F344/Crl rats were administered intratracheally 1 nmol of 14C-labelled anthracene (AN), benz[a]anthracene (BA), 1-nitropyrene (NP), 6-nitrobenzo[a]pyrene (6-NBP), or dibenzo[c,g]carbazole (DBC). At various times after instillation rats were sacrificed and the amount of 14C remaining in the lungs was determined. Octanol/water partition coefficients were experimentally determined for each of the PAH used. Clearance of 14C from rat lungs following instillation of the different PAH was biphasic. In all cases, greater than 85% of the initial dose instilled was cleared with a half-time of less than 1 h. The half-times for clearance of the residual 14C (1-15% of the dose) were 26, 30, 36, 53 and 63 h for AN, NP, 6-NBP, BA and DBC, respectively. The log of the octanol/water partition coefficients for the different PAH examined ranged from 4.1 (AN) to 6.05 (DBC). Plots of the octanol/water coefficients vs. the long-term clearance half-time for the PAH indicated a linear correlation (p less than 0.001; r2 = 0.96). The results from this study indicate that the greater the lipophilicity of the PAH, the slower the long-term clearance of a small fraction (1-15%) of PAH from rat lungs. These data suggest that predictions of long-term lung clearance can be made for PAH with log octanol/water partition coefficients between 4 and 6.
吸入多环芳烃（PAH）后肺内滞留情况的研究表明，一般而言，PAH会迅速从呼吸道清除。PAH从肺部的清除情况最好用双相清除来描述，清除曲线的长期成分半衰期大于24小时。本研究的目的是确定各种PAH的亲脂性（用正辛醇/水分配系数P衡量）与大鼠肺内PAH的短期和长期清除半衰期之间是否存在关系。给雌性F344/Crl大鼠气管内注入1纳摩尔的14C标记蒽（AN）、苯并[a]蒽（BA）、1-硝基芘（NP）、6-硝基苯并[a]芘（6-NBP）或二苯并[c,g]咔唑（DBC）。注入后不同时间处死大鼠，测定肺内剩余的14C量。对所用的每种PAH通过实验测定正辛醇/水分配系数。注入不同PAH后大鼠肺内14C的清除是双相的。在所有情况下，注入初始剂量的85%以上在不到1小时的半衰期内被清除。AN、NP、6-NBP、BA和DBC清除残余14C（剂量的1%-15%）的半衰期分别为26、30、36、53和63小时。所检测的不同PAH的正辛醇/水分配系数的对数值范围为4.1（AN）至6.05（DBC）。PAH的正辛醇/水系数与长期清除半衰期的关系图显示呈线性相关（p小于0.001；r2 = 0.96）。本研究结果表明，PAH的亲脂性越强，大鼠肺内一小部分（1%-15%）PAH的长期清除速度越慢。这些数据表明，对于正辛醇/水分配系数对数值在4至6之间的PAH，可以预测其长期肺清除情况。
