Collier C G, Morris K J, Launder K A, Humphreys J A, Morgan A, Eastes W, Townsend S
Biomedical Research, AEA Technology, Didcot, Oxon, United Kingdom.
Regul Toxicol Pharmacol. 1994 Dec;20(3 Pt 2):S89-103.
Potential carcinogenicity of fibers is believed to be determined by three factors: the dose, dimensions and durability of the fibers concerned. Currently there is considerable debate on the appropriateness of using results from intraperitoneal (i.p.) injection studies to predict the potential carcinogenicity of airborne fibers following inhalation. For ip results to have any significance to potential inhalation hazards, there should be some relation between the biopersistence, dose, and dose distribution of fibers in the serosal cavity and in the lung. Preliminary results on the durability of one experimental glass fiber in the peritoneal cavity suggest differences in dissolution when compared with durability in the lung. In the lung, the diameters of the long fibers (> 20 microns) were observed to decline at a rate consistent with their exposure to a neutral pH environment. The diameter of shorter fibers declined much more slowly, consistent with exposure to a more acidic environment such as is found in the phagolysosomes of alveolar macrophages. In the peritoneal cavity all fibers, regardless of length, dissolved at the same rate as short fibers in the lung. The effect of dose on the distribution of fibers in the peritoneal cavity was investigated using similar experimental glass fibers and compared with that of a powder made from ground fibers. For both materials at doses up to 1.5 mg, material was taken up by the peritoneal organs roughly in proportion to their surface area. This uptake was complete 1-2 days after injection. At higher doses, the majority of the material in excess of this 1.5 mg formed clumps of fibers (nodules) which were either free in the peritoneal cavity or loosely bound to peritoneal organs. These nodules displayed classic foreign body reactions with an associated granulomatous inflammatory response. The findings on both durability in the peritoneal cavity and the presence of two distinct populations of material following i.p. injection have implications for the justification of the use of i.p. injections to assess potential carcinogenicity of fibers following inhalation.
相关纤维的剂量、尺寸和耐久性。目前，关于使用腹腔内（i.p.）注射研究结果来预测吸入后空气中纤维的潜在致癌性是否合适存在相当大的争议。要使腹腔内注射结果对潜在吸入危害有任何意义，浆膜腔和肺中纤维的生物持久性、剂量和剂量分布之间应该存在某种关系。一种实验性玻璃纤维在腹腔内耐久性的初步结果表明，与在肺中的耐久性相比，其溶解情况存在差异。在肺中，观察到长纤维（>20微米）的直径以与其暴露于中性pH环境一致的速率下降。较短纤维的直径下降得慢得多，这与暴露于更酸性环境（如肺泡巨噬细胞吞噬溶酶体中发现的环境）一致。在腹腔内，所有纤维，无论长度如何，溶解速率与肺中的短纤维相同。使用类似的实验性玻璃纤维研究了剂量对纤维在腹腔内分布的影响，并与由磨碎纤维制成的粉末的影响进行了比较。对于两种材料，在剂量高达1.5毫克时，材料被腹腔器官摄取的量大致与其表面积成比例。这种摄取在注射后1 - 2天完成。在更高剂量下，超过1.5毫克的大部分材料形成纤维团块（结节），这些结节要么在腹腔内游离，要么松散地附着在腹腔器官上。这些结节表现出典型的异物反应以及相关的肉芽肿性炎症反应。关于腹腔内耐久性以及腹腔内注射后存在两种不同物质群体的研究结果，对于使用腹腔内注射来评估吸入后纤维潜在致癌性的合理性具有启示意义。
