Hesterberg T W, Hart G A, Chevalier J, Miiller W C, Hamilton R D, Bauer J, Thevenaz P
Johns Manville Technical Center, Littleton, Colorado, USA.
Toxicol Appl Pharmacol. 1998 Nov;153(1):68-82. doi: 10.1006/taap.1998.8522.
The chronic inhalation effects in rats of X607 (a rapidly dissolving synthetic vitreous fiber) were compared with those previously reported for RCF1 (a refractory ceramic synthetic vitreous fiber) and chrysotile asbestos. Of primary concern was the importance of biopersistence as a mechanism of fiber toxicity. Fischer rats were exposed to fiber aerosol by nose-only inhalation for 6 h/day, 5 days/week for 2 years. X607 and RCF1 aerosols were similar in concentration (approximately 200 fibers/cc) and average dimensions (approximately 20 x 1 microns). Chrysotile aerosol was higher in concentration (10,600 fibers/cc) and an order of magnitude smaller in average dimensions. Lung fiber deposition after 6 h inhalation was greater for X607 than for RCF1. However, at later time points, fibers/lung (especially long fibers) were much lower for X607 than for RCF1, suggesting less biopersistence for X607. X607 was neither fibrogenic nor tumorigenic and induced only minimal lung cellularity that reversed after exposure was terminated. In contrast, RCF1 and chrysotile asbestos induced pulmonary fibrosis and thoracic neoplasms (chrysotile induced 32% more pulmonary neoplasms than RCF1). Lung deposition and fiber lengths did not explain the toxicologic differences between the three fibers. Fiber biodurability, including chemical and physical parameters, appears to be a major toxicologic determinant here. Chemical analysis of lung fibers revealed rapid leaching of X607 compared to RCF1. In in vitro dissolution tests, X607 underwent rapid dissolution (kdis = 990 ng/cm2/h) and transverse fragmentation, RCF1 dissolved slowly (kdis = 6 ng/cm2/h) and did not fragment, and chrysotile dissolution was negligible (< 0.1 ng/cm2/h).
将X607（一种快速溶解的合成玻璃纤维）对大鼠的慢性吸入影响与先前报道的RCF1（一种难熔陶瓷合成玻璃纤维）和温石棉的影响进行了比较。主要关注的是生物持久性作为纤维毒性机制的重要性。将Fischer大鼠通过仅鼻吸入暴露于纤维气溶胶中，每天6小时，每周5天，持续2年。X607和RCF1气溶胶的浓度（约200根纤维/立方厘米）和平均尺寸（约20×1微米）相似。温石棉气溶胶的浓度较高（10,600根纤维/立方厘米），平均尺寸小一个数量级。吸入6小时后，X607的肺纤维沉积比RCF1更多。然而，在随后的时间点，X607的纤维/肺（尤其是长纤维）比RCF1低得多，这表明X607的生物持久性较低。X607既不具有致纤维化性也不具有致瘤性，仅引起最小程度的肺细胞增多，在暴露终止后可逆转。相比之下，RCF1和温石棉会导致肺纤维化和胸内肿瘤（温石棉诱发的肺肿瘤比RCF1多32%）。肺沉积和纤维长度并不能解释这三种纤维之间的毒理学差异。包括化学和物理参数在内的纤维生物耐久性似乎是这里的主要毒理学决定因素。对肺纤维的化学分析显示，与RCF1相比，X607的浸出速度很快。在体外溶解试验中，X607迅速溶解（溶解常数kdis = 990纳克/平方厘米/小时）并发生横向破碎，RCF1溶解缓慢（kdis = 6纳克/平方厘米/小时）且不破碎，温石棉的溶解可忽略不计（< 0.1纳克/平方厘米/小时）。
