Calibration study on subchronic inhalation toxicity of man-made vitreous fibers in rats
Calibration study on subchronic inhalation toxicity of man-made vitreous fibers in rats
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DOI：
10.1080/08958370390229843
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发表时间：
2003-10-01
影响因子：
2.1
通讯作者：
Sintes, JMR
中科院分区：
文献类型：
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作者：
Bellmann, B;Muhle, H;Sintes, JMR
本实验研究了一种特殊用途玻璃微纤维（E-glass微纤维）、石棉纤维MMVF21和一种新型高温应用纤维（钙镁硅酸纤维，CMS）在Wistar大鼠体内3个月的生物效应。将大鼠每天6小时、每周5天，连续3个月暴露于e -玻璃微纤维和MMVF21的纤维气溶胶浓度分别为约15、50和150纤维/ml（纤维长度> 20 μ m）。对于CMS纤维，只使用最高暴露浓度。在暴露后3个月期间，研究恢复效果。在最高暴露浓度组中，e -玻璃微纤维的重量浓度为17.2 mg/m(3)， MMVF21为37 mg/m(3)， CMS纤维为49.5 mg/m(3)。暴露3个月后，e -玻璃超细纤维的肺滞留量大于20 μ m /肺为17 × 10(6)， MMVF21为5.7 × 10(6)， CMS为0.88 × 10(6)。恢复3个月后，与原始肺负荷相比，e -玻璃微纤维、MMVF21和CMS的长纤维组分浓度分别降至38.4%、63.9%和3.0%。测量的生物效应包括炎症和增殖潜力、组织病理学病变以及这些效应在3个月恢复期的持续性。通常，与MMVF21相比，e -玻璃微纤维观察到的效应更高。e-玻璃微纤维和MMVF21暴露对肺重量、测定生化参数和支气管肺泡灌洗液（BALF）中多形核白细胞（PMN）的增加、末细支气管上皮细胞增殖（brdu反应）和间质纤维化有明显的剂量依赖性影响。对致癌性e -玻璃微纤维的增殖试验结果表明，该试验对潜在致癌性具有重要的预测价值。令人惊讶的是，对于生物可溶性的CMS纤维，在本研究中检测到成纤维潜力。CMS暴露组的结果表明，影响可能主要是由非纤维颗粒的存在决定的，如果纤维制备中含有大量的非纤维颗粒，那么纤维化可能不是纤维样品致癌活性的预测因子。综上所述，本研究证明了颗粒成分对纤维粉尘污染的重要性。对于未来的亚慢性研究，建议延长治疗后的观察期。
This 3-mo inhalation study investigated the biological effects of a special-purpose glass microfiber (E-glass microfiber), the stone wool fiber MMVF21, and a new high-temperature application fiber (calcium-magnesium-silicate fiber, CMS) in Wistar rats. Rats were exposed 6 h/day, 5 days/wk for 3 mo to fiber aerosol concentrations of approximately 15, 50, and 150 fibers/ml ( fiber length > 20 mum) for E-glass microfiber and MMVF21. For the CMS fiber only the highest exposure concentration was used. During a 3-mo postexposure period, recovery effects were studied. In the highest exposure concentration groups, gravimetric concentrations were 17.2 mg/m(3) for E-glass microfiber, 37 mg/m(3) for MMVF21, and 49.5 mg/m(3) for the CMS fiber. After 3 mo of exposure, lung retention of fibers longer than 20 mum per lung was 17 x 10(6) for E-glass microfiber, 5.7 x 10(6) for MMVF21, and 0.88 x 10(6) for CMS. After 3 mo of recovery the concentration of the long fiber fraction was decreased to 38.4%, 63.9%, and 3.0% compared to original lung burden for the E-glass microfiber, MMVF21, and CMS, respectively. Biological effects measured included inflammatory and proliferative potential, histopathology lesions, and the persistence of these effects over a recovery period of 3 mo. Generally, observed effects were higher for E-glass microfiber when compared to MMVF21. The following clear dose-dependent effects on E-glass microfiber and MMVF21 exposure were observed as main findings of the study: increase in lung weight, in measured biochemical parameters and polymorphonuclear leukocytes (PMN) in the bronchoalveolar lavage fluid (BALF), in cell proliferation (BrdU-response) of terminal bronchiolar epithelium, and in interstitial fibrosis. The values observed in the proliferation assay on the carcinogenic E-glass microfiber indicate that this assay has an important predictive value with regards to potential carcinogenicity. Surprisingly, for the biosoluble CMS fiber, fibrogenic potential was detected in this study. The results of the CMS exposure group indicate that effects may be dominated by the presence of nonfibrous particles and that fibrosis may not be a predictor of carcinogenic activity of fiber samples, if the fiber preparation contains a significant fraction of nonfibrous particles. In summary, this study demonstrates the importance of fiber dust contamination by granular components. For future subchronic studies a longer posttreatment observation period would be advisable.