Maxim L D, Mast R W, Utell M J, Yu C P, Boymel P M, Zoitos B K, Cason J E
Everest Consulting Associates, Inc., Cranbury, New Jersey 08512, USA.
Regul Toxicol Pharmacol. 1999 Aug;30(1):54-74. doi: 10.1006/rtph.1999.1314.
Isofrax and Insulfrax are two new synthetic vitreous fibers (SVFs) developed for high-temperature insulation (1800-2300 degrees F) applications. In an attempt to significantly reduce or eliminate the potential of adverse health effects, these two fibers were specifically designed to have high solubility and, thus, low in vivo biodurability. In this paper, we review the effects of chemical composition on biodurability, in vitro fiber dissolution rates (K(dis)), and the relevance and relationship of K(dis) to pulmonary fibrosis and lung tumors in chronic rat inhalation studies. We also examine the correlations between K(dis) and weighted in vivo half-life (t(0.5)) of long fibers (>20 microm) and their relation to pulmonary effects in chronic rat inhalation bioassays. Predictions for outcomes of inhalation bioassays and development of nonsignificant risk levels of exposure are provided. Additionally, justification for the use of inhalation versus noninhalation animal data is provided as is a brief review of human health effects of SVFs. We conclude, inter alia, that Isofrax and Insulfrax have low biodurability, would not be expected to produce either pulmonary fibrosis or lung tumors in a well-designed animal inhalation bioassay, have weighted half-lives beneath the threshold established by the European Union for classification as a carcinogen, and based on epidemiological data for SVFs would not be expected to result in incremental cancer in human cohorts. Finally, it is estimated that approximately 90% of workplace exposure concentrations of these materials would be beneath 1 f/cc. At a concentration of 1 f/cc, neither fiber would be expected to result in an incremental working lifetime cancer risk greater than 10(-5).
异弗rax和因苏尔弗rax是两种新开发的用于高温隔热（1800 - 2300华氏度）应用的合成玻璃纤维（SVF）。为了显著降低或消除潜在的健康不良影响，这两种纤维经过特殊设计，具有高溶解性，因此体内生物耐久性较低。在本文中，我们回顾了化学成分对生物耐久性、体外纤维溶解速率（K(dis)）的影响，以及在慢性大鼠吸入研究中K(dis)与肺纤维化和肺肿瘤的相关性及关系。我们还研究了长纤维（>20微米）的K(dis)与体内加权半衰期（t(0.5)）之间的相关性及其在慢性大鼠吸入生物测定中与肺部效应的关系。提供了吸入生物测定结果的预测以及非显著暴露风险水平的制定。此外，还提供了使用吸入与非吸入动物数据的理由以及对合成玻璃纤维对人类健康影响的简要综述。我们特别得出结论，异弗rax和因苏尔弗rax具有低生物耐久性，在精心设计的动物吸入生物测定中预计不会产生肺纤维化或肺肿瘤，加权半衰期低于欧盟确定的致癌物分类阈值，并且根据合成玻璃纤维的流行病学数据，预计不会在人类群体中导致额外的癌症。最后，据估计，这些材料在工作场所的暴露浓度约90%将低于1根/立方厘米。在浓度为1根/立方厘米时，预计这两种纤维都不会导致工作寿命期间的额外癌症风险大于10^(-5)。
