Natural mineral fibers: conducting inhalation toxicology studies—part B: development of a nose-only exposure system for repeat-exposure <i>in vivo</i> study of Libby amphibole aerosol

Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent <i>in vivo</i> rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m³. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.

接触石棉与恶性及非恶性呼吸系统疾病密切相关。为强化纤维类物质风险评估的科学依据，美国国家环境卫生科学研究所（National Institute of Environmental Health Sciences, NIEHS）启动了一系列研究，旨在解答吸入暴露后天然石棉及相关矿物纤维的毒理学基础问题。此前已开发并验证了一套原型仅鼻暴露染毒系统。本研究将该原型系统升级为大型染毒系统，用于后续以利比角闪石（Libby amphibole, LA）2007作为模式纤维的体内（in vivo）啮齿动物吸入染毒研究。该暴露系统包含6个暴露转盘，可独立向每个转盘输送稳定的LA 2007气溶胶，目标浓度分别为0（对照组）、0.1、0.3、1、3或10 mg/m³。本研究采用单台气溶胶发生器为所有转盘提供气溶胶，以确保各暴露环境的化学与物理特性保持一致，仅气溶胶浓度为各转盘间的唯一核心变量。对暴露端口采集的气溶胶样本开展的透射电子显微镜（Transmission Electron Microscopy, TEM）联用能量色散光谱法（Energy Dispersive Spectrometry, EDS）及选区电子衍射（Selected Area Electron Diffraction, SAED）分析结果显示，各暴露转盘的纤维尺寸、化学成分及矿物学特征均保持一致，且与原始LA 2007样品的特性相当。本研究开发的暴露系统已就绪，可用于开展大鼠LA 2007的仅鼻吸入染毒毒性研究。该暴露系统预计还可应用于其他受关注天然矿物纤维的吸入毒性评估。