Turim J, Brown R C
Sciences International, Inc., 1800 Diagonal Road, Alexandria, VA 22314, USA.
Inhal Toxicol. 2003 Sep 15;15(11):1103-18. doi: 10.1080/08958370390228556.
Refractory ceramic fibers (RCFs) are man-made vitreous fibers commonly used in insulation applications above 1000 degrees C. Although they have been subjected to considerable toxicologic evaluation, only the pooled results from two rat inhalation studies provide data that may be suitable for performing a numerical risk assessment. Even in these inhalation studies, good evidence exists that the maximum tolerated dose (MTD) was exceeded and that pulmonary overload occurred, a condition that will cause tumors whatever the dust responsible. Indeed, a significant yield of tumors was only obtained at the highest dose tested. If these results are omitted, there is no statistically significant evidence of carcinogenicity within the RCF results. Although there is little evidence that overload-related tumors are relevant to human risk, we adopted a conservative approach to obtain the estimates of risk regardless of overload, using a biologically based model, the two-stage clonal expansion model, as well as various statistical models, including the benchmark dose model. We argue that the data favor the use of a biologically based model, which gives the best fit when the highest dose RCF exposures are omitted. Continuing with this model, we show that available data from the RCF experiment, less outliers, coupled with results from other experiments with man-made mineral fibers (MMVFs), demonstrate that all MMVFs are potentially carcinogenic, with any risk mediated by the fibers' biopersistence. Application of this "all MMVF data set" model yields a maximum likely estimate for RCF excess unit risk of 4.6 x 10(-5) (95% upper confidence limit = 9.2 x 10(-5) per fiber/ml). This implies that the risk from occupational exposure to RCFs at 1 fiber/ml for a typical working lifetime would not exceed 10(-4).
难熔陶瓷纤维（RCFs）是一种人造玻璃纤维，常用于1000摄氏度以上的隔热应用。尽管它们已经接受了大量的毒理学评估，但只有两项大鼠吸入研究的汇总结果提供了可能适用于进行数值风险评估的数据。即使在这些吸入研究中，也有充分的证据表明超过了最大耐受剂量（MTD）并且发生了肺部过载，无论何种粉尘导致这种情况，都会引发肿瘤。事实上，仅在测试的最高剂量下才获得了显著的肿瘤发生率。如果省略这些结果，在RCF的结果中就没有统计学上显著的致癌证据。尽管几乎没有证据表明与过载相关的肿瘤与人类风险相关，但我们采用了一种保守的方法来获得无论过载情况如何的风险估计，使用基于生物学的模型、两阶段克隆扩增模型以及各种统计模型，包括基准剂量模型。我们认为数据支持使用基于生物学的模型，当省略最高剂量的RCF暴露时，该模型拟合效果最佳。继续使用该模型，我们表明来自RCF实验的可用数据（去除异常值），再加上其他人造矿物纤维（MMVFs）实验的结果，表明所有MMVFs都具有潜在致癌性，任何风险都由纤维的生物持久性介导。应用这个“所有MMVF数据集”模型得出RCF额外单位风险的最大可能估计值为4.6×10^(-5)（95%上置信限 = 每纤维/毫升9.2×10^(-5)）。这意味着在典型的工作寿命期间，职业接触每毫升1根纤维的RCF所带来的风险不会超过10^(-4)。
