Searl A, Buchanan D, Cullen R T, Jones A D, Miller B G, Soutar C A
Institute of Occupational Medicine, Edinburgh, UK.
Ann Occup Hyg. 1999 Apr;43(3):143-53.
The study objectives were to assess the ability of intratracheal injection methods to discriminate between nine fibre types in respect of pulmonary biopersistence, and to provide approximate estimates of relative biopersistence and durability for a study of general relationships with biological and toxicological responses. The test fibres included six samples of size-selected fibre types specially prepared for research purposes, two commercially available fibres, and amosite. A 1 mg dose of each fibre type was administered to rats by intratracheal injection. The relative biopersistence of fibres in different size categories was assessed from the changes in mean lung burden, as determined by electron microscopy, at 3 days and 1, 6 and 12 months after injection. The ability of the test materials to resist dissolution was measured in a parallel series of simple in vitro acellular experiments at two pHs and in a continuous flow dissolution test. The observed differences in the persistence of fibres of differing length recovered from rat lungs were consistent with the current hypothesis that short fibres are cleared by cellular processes and long fibres by dissolution and disintegration. Differences in persistence of long (> 20 microns) fibres were correlated with measured rates of dissolution in vitro. Differences in persistence among those fibre types also studied by others workers were consistent with their findings after inhalation and intratracheal injection. Overall, the differences in the biopersistences of the test fibres following intratracheal injection were sufficient to enable an examination of the relationship of biopersistence with other biological and toxicological responses. Biopersistence was influenced by both fibre dimensions and solubility.
本研究的目的是评估气管内注射法区分九种纤维类型在肺部生物持久性方面的能力,并为研究与生物学和毒理学反应的一般关系提供相对生物持久性和耐久性的近似估计。测试纤维包括六个为研究目的专门制备的尺寸选择纤维类型的样品、两种市售纤维和铁石棉。通过气管内注射给大鼠施用1mg每种纤维类型的剂量。根据注射后3天以及1、6和12个月时通过电子显微镜测定的平均肺负荷变化,评估不同尺寸类别的纤维的相对生物持久性。在两个pH值下的一系列平行简单体外无细胞实验以及连续流动溶解试验中测量测试材料抵抗溶解的能力。从大鼠肺中回收的不同长度纤维的持久性观察到的差异与当前的假设一致,即短纤维通过细胞过程清除,长纤维通过溶解和崩解清除。长(>20微米)纤维持久性的差异与体外测量的溶解速率相关。其他研究人员也研究的那些纤维类型之间的持久性差异与他们吸入和气管内注射后的发现一致。总体而言,气管内注射后测试纤维的生物持久性差异足以检验生物持久性与其他生物学和毒理学反应的关系。生物持久性受纤维尺寸和溶解度两者的影响。