Berman D W, Crump K S, Chatfield E J, Davis J M, Jones A D
ICF Kaiser Engineers, Oakland, California, USA.
Risk Anal. 1995 Apr;15(2):181-95. doi: 10.1111/j.1539-6924.1995.tb00312.x.
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 > or = 20 microns 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 (> or = 5 microns) thin (0.4 microns) fibers and bundles, with a possible contribution by long and very thick (> or = 5 microns) complex clusters and matrices. Potency appears to increase with increasing length, with structures longer than 40 microns being about 500 times more potent than structures between 5 and 40 microns in length. Structures < 5 microns 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.
在吸入研究中，AF/HAN大鼠暴露于九种不同类型的石棉粉尘（共13个独立实验），其数据用于统计分析，以确定是否能找到一种石棉暴露量度（以具有特定大小、形状和矿物学特征的结构浓度表示），该量度能令人满意地预测实验中观察到的肺癌或间皮瘤发病率。由于原始研究中石棉结构表征存在局限性，通过使用直接转移技术对重新生成的原始粉尘样本进行透射电子显微镜分析，制定了新的暴露量度。该分析提供了每个单独结构的矿物学（即温石棉、铁石棉、青石棉或透闪石）、类型（即纤维、束、簇或基质）、大小（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。尽管与肿瘤发病率相关性最高的量度是长度大于或等于20微米的结构浓度，但未发现单一暴露量度能充分描述吸入研究中观察到的肺癌反应。已确定多元暴露量度能充分描述肺癌反应。导致肺癌风险的结构似乎是长（大于或等于5微米）细（0.4微米）的纤维和束，长且非常厚（大于或等于5微米）的复杂簇和基质可能也有作用。效力似乎随长度增加而增强，长度超过40微米的结构的效力约为长度在5至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风险没有任何影响。该分析未发现温石棉和闪石诱发肺癌的效力有差异。然而，矿物学在间皮瘤的诱发中似乎很重要，温石棉的效力低于闪石。
