Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc.
Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc.
复制标题
大鼠和小鼠重复吸入滑石粉 20 天后滑石粉沉积和影响。
DOI：
10.1016/s0013-9351(89)80069-6
复制
发表时间：
1989
影响因子：
8.3
通讯作者：
Brown,SC
中科院分区：
文献类型：
--
作者：
Pickrell,JA;Snipes,MB;Benson,JM;Hanson,RL;Jones,RK;Carpenter,RL;Thompson,JJ;Hobbs,CH;Brown,SC
使用20只F344/Crl大鼠和20只B6 C3 F1小鼠（10只雄性和10只雌性）暴露于三种浓度的无石棉滑石粉中的一种，每天6小时，每周5天，持续4周，研究了滑石粉的吸入暴露浓度与由此产生的肺负荷和组织学病变之间的关系。对照组使用相同的时间表暴露于过滤空气。评价滑石粉的肺滞留和肺病理学的发展。滑石粉气溶胶的质量中值空气动力学直径（MMAD）为3.0 μm，几何标准差（σg）为1.9。大鼠的平均暴露浓度为0、2.3、4.3和17 mg滑石粉/m3。吸入暴露20天后，大鼠的肺负荷平均为0、0.07、0.17和0.72 mg滑石粉/g肺;因此，每单位暴露浓度在肺中保留的量随浓度增加而增加。小鼠的平均暴露浓度为0、2.2、5.7和20.4 mg滑石粉/m3，导致肺负荷为0、0.10、0.29和1.0 mg滑石粉/g肺;因此，暴露浓度与肺中保留量之间的关系大致恒定。本研究的肺负荷用于预测啮齿类动物和人类长期暴露导致的肺负荷。在最后一次暴露日后24小时处死前，在大鼠或小鼠中未观察到临床体征。肺组织的组织学变化仅包括暴露于最高水平滑石粉20天的大鼠和小鼠组肺泡腔内含滑石粉的游离巨噬细胞的中度、弥漫性增加。模拟大鼠和小鼠长期滑石粉吸入暴露的模型预测，如果动物暴露于17 mg滑石粉/m3 2年，滑石粉的沉积和清除率未因持续暴露而改变，则肺负荷为2-3 mg滑石粉/g肺（湿重）。该建模的潜在局限性是，如果滑石粉的清除因持续暴露而延迟，则累积的滑石粉肺负荷将高于模拟模型预测的负荷。暴露于可吸入滑石粉气溶胶的人类预计会累积比暴露于相同气溶胶的啮齿动物高得多的肺负荷，因为人类具有较高的沉积分数和较慢的沉积滑石粉粉尘清除率。对于处于或接近滑石粉TLV的人体暴露量，预测平衡肺负荷为≤ 2 mg滑石粉/g肺。
The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F1mice (10 male and 10 female) exposed to one of three concentrations of asbestosfree talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 μm with a geometric standard deviation (σg) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2–3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated talc lung burdens would be higher than those projected by the simulation model. Humans exposed to aerosols of respirable talc are projected to accumulate much higher lung burdens than would occur in rodents exposed to the same aerosol, because humans have a higher estimated deposition fraction and slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of ⩾2 mg talc/g lung were predicted for human exposures at or near the TLV for talc.