Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.
Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.
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DOI：
10.1089/aivt.2018.0004
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发表时间：
2018-06-01
影响因子：
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通讯作者：
Hayden, Patrick J
中科院分区：
文献类型：
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作者：
Jackson, George R Jr;Maione, Anna G;Hayden, Patrick J
导言：了解潜在的急性吸入毒性对于确定化学品和消费品的安全使用非常重要。目前在世界各国政府监管系统内接受的吸入毒性测试和分类程序主要依赖于在动物中进行的测试。目前工作的目标是开发和预验证一种非动物（体外）试验，用于使用EpiAirway体外人体气道模型确定急性吸入毒性，作为目前公认的动物试验的潜在替代方案。材料与方法：体外试验方法将EpiAirway组织暴露于试验化学品3小时，然后测量组织活力作为试验终点。59种化学品涵盖了广泛的毒性类别，化学结构和物理特性进行了评估。利用体外毒性数据建立预测模型，将化学品分为与目前接受的全球统一制度（GHS）和环境保护署（EPA）制度相对应的类别。结果如下：EpiAirway预测模型识别了基于大鼠的体内GHS急性吸入毒性1-2类和EPA急性吸入毒性I-II类化学物质，对于GHS和EPA急性吸入毒性系统，灵敏度为100%，特异性分别为43.1%和50.0%。EpiAirway预测模型识别GHS特异性靶器官毒性-单次暴露（STOT-SE）1类人类毒物的灵敏度和特异性分别为75.0%和56.5%。腐蚀性和亲电性和氧化反应性似乎是大多数剧毒化学品的主要毒性机制。结论：这些结果表明，EpiAirway试验是目前公认的急性吸入毒性动物试验的一种有前途的替代方法。
Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation toxicity using the EpiAirway in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.