DISPOSITION AND METABOLISM OF [C-14] DIBENZO[C,G]CARBAZOLE AEROSOLS IN RATS AFTER INHALATION
DISPOSITION AND METABOLISM OF [C-14] DIBENZO[C,G]CARBAZOLE AEROSOLS IN RATS AFTER INHALATION
复制标题
DOI：
10.1016/0272-0590(86)90199-5
复制
发表时间：
1986-07-01
期刊：
影响因子：
--
通讯作者：
MCCLELLAN, RO
中科院分区：
文献类型：
--
作者：
BOND, JA;AYRES, PH;MCCLELLAN, RO
二苯并[c，g]咔唑（DBC）是一种含氮多环芳烃，已在烟草焦油，工业油和柴油发动机废气中检测到。DBC在仓鼠的呼吸道组织和小鼠的肺、肾和肝中具有致癌性。本研究的目的是确定吸入DBC后大鼠呼吸道沉积、组织分布、代谢和排泄。将大鼠仅鼻暴露于1.1或13 μ g [14 C]DBC/升空气60分钟。两种浓度的DBC的活性中值空气动力学直径范围为0.7至0.8 μ m。在暴露后不同时间采集尿液、粪便和选定组织。1.1和13 μ g/L暴露浓度的沉积分数相似，分别为13和16%。暴露于任一浓度的DBC后，14 C的主要排泄途径是粪便，约占消除的14 C总量的95%。粪便排泄的半衰期为20 ±。6小时（.hivin.x . ±. SE）。[14 C]DBC的胃肠道吸收为43%。放射性广泛分布于检查的所有组织中，呼吸道（肺、气管、喉和鼻甲）、上消化道（胃和小肠）、肝脏和肾上腺在暴露后1小时内含有最高浓度的[14 C]DBC当量。在检测的两种浓度的DBC下，14 C从组织中的清除都很迅速，大约60 - 98%的初始组织负荷被清除，半衰期范围为1 - 16小时。组织中剩余的2 - 40%被清除，半衰期范围为1.5 - 14天。在尿液和粪便中检测到几种代谢产物，似乎都不是葡糖苷酸或硫酸盐结合物。在尿液中检测到少量的[14 C]DBC，尽管数量小于[14 C]DBC初始呼吸道负荷的1%。这项研究的结果表明，DBC从肺部迅速吸收并转移到许多组织。在消除之前，主要在粪便中，DBC被广泛代谢。暴露浓度对吸入DBC的毒代动力学无影响。
Dibenzo[c,g]carbazole (DBC) is a nitrogen-containing polycyclic aromatic hydrocarbon that has been detected in tobacco tars, industrial oils, and diesel engine exhaust fumes. DBC is carcinogenic in respiratory tract tissue of hamsters and in lungs, kidneys, and livers of mice. The purpose of this research was to determine the respiratory tract deposition, distribution in tissues, metabolism, and excretion of DBC in rats after inhalation. Rats were exposed nose-only to 1.1 or 13 .mu.g [14C]DBC/liter air for 60 min. Activity median aerodynamic diameters for the two concentrations of DBC ranged from 0.7 to 0.8 .mu.m. Urine, feces, and selected tissues were collected for various times after exposure. The fractional deposition for the 1.1 and 13 .mu.g/liter exposure concentrations was similar, 13, and 16%, respectively. The dominant route of excretion of 14C following exposure to either concentration of DBC was the feces, accounting for approximately 95% of the total 14C eliminated. Half-time for fecal excretion was 20 .+-. 6 hr (.hivin.x .+-. SE). Gastrointestinal absorption of [14C]DBC was 43%. Radioactivity was widely distributed to all tissues examined, with the respiratory tract (lung, trachea, larynx, and nasal turbinates), upper gastrointestinal tract (stomach and small intestine), the liver, and the adrenals containing the highest concentrations of [14C]DBC equivalents within 1 hr after exposure. At both concentrations of DBC tested, clearance of 14C from tissues was rapid, with approximately 60 to 98% of the initial tissue burden being cleared with half-times ranging from 1 to 16 hr. The remaining 2 to 40% in the tissues was cleared with half-times that ranged from 1.5 to 14 days. Several metabolites were detected in the urine and feces, none of which appeared to be either glucuronide or sulfate conjugates. Small quantities of [14C]DBC were detected in the urine, although quantities were less than 1% of the initial respiratory tract burden of [14C]DBC. The results from this research indicate that DBC was rapidly absorbed from the lungs and translocated to many tissues. Prior to elimination, primarily in the feces, DBC was extensively metabolized. There appeared to be no effect of exposure concentration on the toxicokinetics of inhaled DBC.