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基于化学成分和维度的不同矿物纤维的间皮瘤效力因素的经验模型。

Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality.

机构信息

a Chemistry and Industrial Hygiene, Inc. , Wheat Ridge , CO , USA.

出版信息

Inhal Toxicol. 2019 Apr;31(5):180-191. doi: 10.1080/08958378.2019.1640320. Epub 2019 Jul 22.

DOI:10.1080/08958378.2019.1640320
PMID:31328588
Abstract

The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Mesothelioma potency factors () for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO, total Fe oxides or total equivalent Fe as FeO, and MgO. Modeled potency factors increase as the aspect ratio, SiO, and total Fe oxide (or FeO) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999,  < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.

摘要

各种矿物纤维类型产生间皮瘤的效力先前已在众多队列中进行了评估,但不同纤维类型的效力差异尚未得到解释。本研究旨在开发一种经验模型,该模型可以根据纤维的化学成分和维度,基于各种纤维类型的化学组成和维度,重建间皮瘤效力因素。获得了典型的化学成分和维度指标(纵横比),并将其与霍奇森和达顿方法估计的间皮瘤效力因素相结合,用于魁北克温石棉、南非青石棉、南非和澳大利亚透闪石、俄罗斯阳起石、利比角闪石和土耳其直闪石。利用向前逐步对数-对数回归方法确定输入参数的最佳组合。利用选定队列中纤维的中位数纵横比以及 SiO2、总 Fe 氧化物或总等效 Fe 作为 FeO 和 MgO 的等效分数,有效地重建了间皮瘤效力因素()。模型化的效力因素随着纵横比、SiO2 和总 Fe 氧化物(或 FeO)含量的增加而增加,而随着 MgO 含量的减少而减少。达到了高达 0.999、<0.01 的相关系数。这些模型还为其他纤维类型的间皮瘤效力提供了合理的估计,包括玻利维亚青石棉、俄罗斯温石棉、氟镁闪石等。尽管采用了经验方法,但所提出的模型通过阐明重要的促成物理化学因素,为间皮瘤机制的靶向研究提供了起点。这些模型具有探索性和初步性质,但有可能有助于引入纤维状矿物质毒理学的定量构效关系方法。

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