Warheit D B, Snajdr S I, Hartsky M A, Frame S R
DuPont Haskell Laboratory, Newark, DE 19714, USA.
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1219-22. doi: 10.1289/ehp.97105s51219.
This study compared pulmonary effects of para-aramid respirable-sized, fiber-shaped particles (RFP) (p-aramid fibrils) and chrysotile asbestos fiber exposures in rats. Additional p-aramid inhalation studies were conducted in hamsters to compare species responses. The hamster results are preliminary. The parameters studied were clearance/biopersistence of inhaled p-aramid RFP or size-separated asbestos fibers as well as pulmonary cell proliferation and inflammation indices after 2-week inhalation exposures. Rats were exposed nose only to chrysotile asbestos fibers at concentrations of 459 and 782 fibers/ml or to p-aramid RFP at 419 or 772 fibrils/ml. Hamsters were exposed whole body to p-aramid RFP at concentrations of 358 and 659 fibrils/ml. Subsequently, animals were assessed immediately (time 0) as well as 5 days (10 days for hamsters), 1, 3, 6, and 12 months postexposure. Lung burdens for the p-aramid-exposed rats were 4.8 x 10(7) and 7.6 x 10(7) fibrils/lung, with similar numbers of chrysotile fibers > 5 microns recovered from the lungs of asbestos-exposed rats. In comparison, 1.4 x 10(6) fibrils/lung were recovered in the high-dose hamster group. Biopersistence studies in p-aramid-exposed rats and hamsters demonstrated an initial increase (relative to time 0) in retained p-aramid fibrils during the first month postexposure, which indicated breakage or shortening of inhaled fibrils. This result was associated with a progressive reduction, and increased residence time in the lung, in the mean lengths of the fibrils, which signified biodegradability of inhaled p-aramid fibrils in both species. In contrast, clearance of short chrysotile asbestos fibers was rapid, but clearance of the long chrysotile fibers was slow or insignificant, as evidenced by a progressive increase over time in the mean lengths of fibers recovered from the lungs of exposed rats. Two-week, high-dose exposures to p-aramid in both rats and hamsters produced transient increases in pulmonary inflammatory and cell proliferative responses. In contrast, inhalation of size-separated chrysotile asbestos fibers in rats produced persistent increases in cell labeling indices of airway, alveolar, and subpleural cells measured through a period of 1 to 3 months postexposure. These results suggest that inhaled p-aramid RFP are biodegradable in the lungs of exposed rats and hamsters. In contrast, exposures to chrysotile asbestos fibers in rats resulted in a selective pulmonary retention of long chrysotile fibers.
本研究比较了对位芳纶可吸入尺寸的纤维状颗粒（RFP）（对位芳纶原纤维）和温石棉纤维对大鼠肺部的影响。还对仓鼠进行了额外的对位芳纶吸入研究，以比较不同物种的反应。仓鼠的研究结果是初步的。所研究的参数包括吸入的对位芳纶RFP或按尺寸分离的石棉纤维的清除/生物持久性，以及吸入暴露2周后的肺细胞增殖和炎症指标。大鼠仅通过鼻腔暴露于浓度为459和782根纤维/毫升的温石棉纤维，或暴露于浓度为419或772根原纤维/毫升的对位芳纶RFP。仓鼠全身暴露于浓度为358和659根原纤维/毫升的对位芳纶RFP。随后，在暴露后立即（时间0）以及暴露后5天（仓鼠为10天）、1、3、6和12个月对动物进行评估。暴露于对位芳纶的大鼠肺部负荷为4.8×10⁷和7.6×10⁷根原纤维/肺，从暴露于石棉的大鼠肺部回收的长度大于5微米的温石棉纤维数量与之相似。相比之下，高剂量仓鼠组回收的原纤维为1.4×10⁶根/肺。对暴露于对位芳纶的大鼠和仓鼠进行的生物持久性研究表明，在暴露后的第一个月，肺部留存的对位芳纶原纤维最初有所增加（相对于时间0），这表明吸入的原纤维发生了断裂或缩短。这一结果与原纤维平均长度的逐渐减少以及在肺部停留时间的增加相关，这意味着吸入的对位芳纶原纤维在两种物种中都具有生物可降解性。相比之下，短温石棉纤维的清除很快，但长温石棉纤维的清除缓慢或不明显，从暴露大鼠肺部回收的纤维平均长度随时间逐渐增加就证明了这一点。在大鼠和仓鼠中，为期两周的高剂量对位芳纶暴露均导致肺部炎症和细胞增殖反应短暂增加。相比之下，大鼠吸入按尺寸分离的温石棉纤维后，在暴露后1至3个月的时间段内，气道、肺泡和胸膜下细胞的细胞标记指数持续增加。这些结果表明，吸入的对位芳纶RFP在暴露的大鼠和仓鼠肺部具有生物可降解性。相比之下，大鼠暴露于温石棉纤维导致肺部选择性留存长温石棉纤维。
