Scientific Consultancy - Animal Welfare, 85579 Neubiberg, Germany.
Department of Material Physics and Analytics, BASF SE, Advanced Materials Research, 67056 Ludwigshafen, Germany.
Chem Res Toxicol. 2021 Mar 15;34(3):780-792. doi: 10.1021/acs.chemrestox.0c00401. Epub 2021 Jan 19.
The hazard potential, including carcinogenicity, of inhaled man-made vitreous fibers (MMVFs) is correlated with their biodurability in the lung, as prerequisite for biopersistence. Abiotic dissolution testing serves to predict biodurability. We re-analyzed the International Agency for Research on Cancer Monograph on MMVFs and found that the correlation between biopersistence and abiotic dissolution presented therein confounded different simulant fluids and further confounded evaluation of leaching vs structural elements. These are critical choices for abiotic dissolution testing, as are binder removal and the rate of the flow that removes ions during testing. Therefore, we experimentally demonstrated how fluid composition and binder affect abiotic dissolution of a representative stone wool MMVF. We compared six simulant fluids (all pH 4.5, reflecting the environment of alveolar macrophage lysosomes) that differed in organic acids, which have a critical role in their ability to modulate the formation of Si-rich gels on the fiber surfaces. Removing the binder accelerates the average dissolution rate by +104% (max. + 273%) across the fluids by suppression of gel formation. Apart from the high-citrate fluid that predicted a 10-fold faster dissolution than is observed , none of the five other fluids resulted in dissolution rates above 400 ng/cm/h, the limit associated with the exoneration from classification for carcinogenicity in the literature. These findings were confirmed with and without binder. For corroboration, five more stone wool MMVFs were assessed with and without binder in one specific fluid. Again, the presence of the binder caused gel formation and reduced dissolution rates. To enhance the reliability and robustness of abiotic predictions of biodurability, we recommend replacing the critically influential citric acid in pH 4.5 fluids with other organic acids. Also, future studies should consider structural transformations of the fibers, including changes in fiber length, fiber composition, and reprecipitation of gel layers.
吸入性人造玻璃纤维（MMVF）的危害潜力，包括致癌性，与其在肺部中的生物持久性相关，这是生物持久性的前提。非生物溶解测试可用于预测生物耐久性。我们重新分析了国际癌症研究机构关于 MMVF 的专论，发现其中生物持久性和非生物溶解之间的相关性混淆了不同的模拟液，并进一步混淆了浸出与结构元素的评估。这些对于非生物溶解测试是关键的选择，就像去除粘合剂以及在测试过程中去除离子的流速一样。因此，我们通过实验证明了流体成分和粘合剂如何影响代表性的石棉 MMVF 的非生物溶解。我们比较了六种模拟液（均为 pH4.5，反映了肺泡巨噬细胞溶酶体的环境），它们在有机酸方面存在差异，有机酸在调节纤维表面形成富硅凝胶的能力方面起着关键作用。去除粘合剂通过抑制凝胶形成，将平均溶解速率提高了+104%（最高+273%）。除了高柠檬酸流体预测的溶解速度比观察到的快 10 倍之外，其余五种流体的溶解速度均未超过 400ng/cm/h，这是文献中致癌性分类豁免的限制。这些发现得到了有和没有粘合剂的证实。为了佐证，在一种特定的流体中，又有五种石棉 MMVF 进行了有和没有粘合剂的评估。同样，粘合剂的存在导致凝胶形成并降低了溶解速率。为了提高非生物预测生物持久性的可靠性和稳健性，我们建议用其他有机酸替代 pH4.5 流体中具有关键影响的柠檬酸。此外，未来的研究还应考虑纤维的结构转变，包括纤维长度、纤维成分和凝胶层的再沉淀的变化。
