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费希尔344大鼠中按尺寸分离的玻璃纤维的慢性吸入毒性

Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats.

作者信息

Hesterberg T W, Miiller W C, McConnell E E, Chevalier J, Hadley J G, Bernstein D M, Thevenaz P, Anderson R

机构信息

Health, Safety, and Environment Department, Mountain Technical Center, Schuller International, Inc., Littleton, Colorado 80162-5005.

出版信息

Fundam Appl Toxicol. 1993 May;20(4):464-76. doi: 10.1006/faat.1993.1057.

DOI:10.1006/faat.1993.1057
PMID:8390950
Abstract

This study was initiated to determine the chronic biological effects in Fisher 344 rats of inhaled size-separated respirable fractions of fibrous glass (FG) having compositions representative of common building insulation wools. Rats were exposed using nose-only inhalation chambers, 6 hr/day, 5 days/week, for 24 months to three concentrations (3, 16, and 30 mg/m3) of two different compositions of FG (designated MMVF 10 and MMVF 11), or to filtered air (negative control). Fibrous glass findings were compared to those from a concurrent inhalation study of chrysotile asbestos and refractory ceramic fiber (RCF). The FGs used in this study were size selected to be largely respirable in the rat and the aerosol generation technique did not alter the dimensions of the fibers. Interim euthanizations took place at 3- to 6-month intervals to monitor progression of pulmonary changes. Fibers were recovered from digested lung tissue for determination of changes in fiber number and morphology. In animals exposed to 30 mg/m3 of MMVF 10 or MMVF 11, 4.2 +/- 0.9 x 10(5) and 6.4 +/- 3.1 x 10(5) fibers/mg dry lung tissue, respectively, were recovered after 24 months of exposure. Exposure to chrysotile asbestos (10 mg/m3) and to a lesser extent RCF (30 mg/m3) resulted in pulmonary fibrosis as well as mesothelioma and significant increases in lung tumors. FG exposure was associated with a nonspecific inflammatory response (macrophage response) in the lungs that did not appear to progress after 6-12 months of exposure. These cellular changes are reversible and are similar to the effects observed after inhalation of an inert dust. No lung fibrosis was observed in the FG-exposed animals. Further, FG exposure resulted in no mesotheliomas and no statistically significant increase in lung tumor incidence when compared to that of the negative control group. These findings, along with previous inhalation studies, suggest that respirable fibrous glass does not represent a significant hazard for fibrotic or neoplastic lung disease in humans.

摘要

开展本研究是为了确定吸入具有普通建筑隔热棉代表性成分的不同粒径可吸入性纤维玻璃(FG)对费希尔344大鼠的慢性生物学效应。使用仅鼻吸入式染毒舱,让大鼠每天暴露6小时,每周暴露5天,持续24个月,暴露于两种不同成分(分别指定为MMVF 10和MMVF 11)的FG的三种浓度(3、16和30 mg/m³)下,或暴露于过滤空气(阴性对照)中。将纤维玻璃的研究结果与同期进行的温石棉和难熔陶瓷纤维(RCF)吸入研究结果进行比较。本研究中使用的FG经过粒径筛选,在大鼠体内基本具有可吸入性,且气溶胶生成技术未改变纤维尺寸。每隔3至6个月进行一次中期安乐死,以监测肺部变化的进展。从消化后的肺组织中回收纤维,以确定纤维数量和形态的变化。在暴露于30 mg/m³的MMVF 10或MMVF 11的动物中,暴露24个月后,每毫克干肺组织分别回收了4.2±0.9×10⁵和6.4±3.1×10⁵根纤维。暴露于温石棉(10 mg/m³)以及在较小程度上暴露于RCF(30 mg/m³)会导致肺纤维化、间皮瘤以及肺肿瘤显著增加。FG暴露与肺部非特异性炎症反应(巨噬细胞反应)相关,在暴露6至12个月后似乎没有进展。这些细胞变化是可逆的,与吸入惰性粉尘后观察到的效应相似。在暴露于FG的动物中未观察到肺纤维化。此外,与阴性对照组相比,FG暴露未导致间皮瘤,且肺肿瘤发生率没有统计学上的显著增加。这些发现以及之前的吸入研究表明,可吸入性纤维玻璃对人类的纤维化或肿瘤性肺部疾病不构成重大危害。

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