THE SIZES, SHAPES, AND MINERALOGY OF ASBESTOS STRUCTURES THAT INDUCE LUNG-TUMORS OR MESOTHELIOMA IN AF/HAN RATS FOLLOWING INHALATION
THE SIZES, SHAPES, AND MINERALOGY OF ASBESTOS STRUCTURES THAT INDUCE LUNG-TUMORS OR MESOTHELIOMA IN AF/HAN RATS FOLLOWING INHALATION
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DOI：
10.1111/j.1539-6924.1995.tb00312.x
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发表时间：
1995-04-01
期刊：
影响因子：
3.8
通讯作者：
JONES, AD
中科院分区：
文献类型：
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作者：
BERMAN, DW;CRUMP, KS;JONES, AD
在吸入研究中，AF/HAN大鼠暴露于9种不同类型的石棉粉尘（在13个单独的实验中），数据被用于统计分析，以确定石棉暴露的测量（表示为具有确定大小，形状和矿化学的结构的浓度）是否可以确定，令人满意地预测实验中观察到的肺肿瘤或间皮瘤发病率。由于原始研究中石棉结构表征的局限性，从原始粉尘的样品中开发了新的暴露措施，这些样品是通过直接转移技术通过透射电子显微镜重新生成和分析的。该分析提供了每个单独结构的矿物学（即温石棉、亚铁石、青橄榄石或透闪石）、类型（即纤维、束、簇或基质）、尺寸（长度和宽度）和复杂性（即簇或基质中可识别成分的数量）的详细信息。虽然与肿瘤发病率相关性最高的测量是长度大于或等于20 μ m的结构的浓度，但没有发现单变量暴露测量能够充分描述吸入研究中观察到的肺肿瘤反应。暴露的多变量测量被确定，可以充分描述肺肿瘤反应。导致肺癌风险的结构似乎是长（大于或等于5微米）薄（0.4微米）的纤维和束，可能是长而非常厚（大于或等于5微米）的复杂簇和基质。效力似乎随着长度的增加而增加，长度超过40微米的结构的效力大约是长度在5到40微米之间的结构的500倍。长度小于5微米的结构似乎对肺癌的风险没有任何贡献。该分析未发现温石棉和角闪石在诱导肺肿瘤方面的效力有差异。然而，矿物学在诱导间皮瘤中似乎很重要，温石棉的作用不如角闪石。
Data from inhalation studies in which AF/HAN rats were exposed to nine different types of asbestos dusts (in 13 separate experiments) are employed in a statistical analysis to determine if a measure of asbestos exposure (expressed as concentrations of structures with defined sizes, shapes and mineralogy) can be identified that satisfactorily predicts the observed lung tumor or mesothelioma incidence in the experiments. Due to limitations in the characterization of asbestos structures in the original studies, new exposure measures were developed from samples of the original dusts that were re-generated and analyzed by transmission electron microscopy using a direct transfer technique. This analysis provided detailed information on the mineralogy (i.e., chrysotile, amosite, crocidolite or tremolite), type (i.e., fiber, bundle, cluster, or matrix), size (length and width) and complexity (i.e., number of identifiable components of a cluster or matrix) of each individual structure.No univariate measure of exposure was found to provide an adequate description of the lung tumor responses observed among the inhalation studies, although the measure most highly correlated with tumor incidence is the concentration of structures greater-than-or-equal-to 20 mum in length. Multivariate measures of exposure were identified that do adequately describe the lung tumor responses. Structures contributing to lung tumor risk appear to be long (greater-than-or-equal-to 5 mum) thin (0.4 mum) fibers and bundles, with a possible contribution by long and very thick (greater-than-or-equal-to5 mum) complex clusters and matrices. Potency appears to increase with increasing length, with structures longer than 40 mum being about 500 times more potent than structures between 5 and 40 mum in length. Structures < 5 mum in length do not appear to make any contribution to lung tumor risk. This analysis did not find a difference in the potency of chrysotile and amphibole toward the induction of lung tumors. However, mineralogy appears to be important in the induction of mesothelioma with chrysotile being less potent than amphibole.