Faber Samantha C, McCullough Shaun D
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina.
Appl In Vitro Toxicol. 2018 Jun 1;4(2):115-128. doi: 10.1089/aivt.2018.0002.
With 7 million deaths reported annually from air pollution alone, it is evident that adverse effects of inhaled toxicant exposures remain a major public health concern in the 21st century. Assessment and characterization of the impacts of air pollutants on human health stems from epidemiological and clinical studies, which have linked both outdoor and indoor air contaminant exposure to adverse pulmonary and cardiovascular health outcomes. Studies in animal models support epidemiological findings and have been critical in identifying systemic effects of environmental chemicals on cognitive abilities, liver disease, and metabolic dysfunction following inhalation exposure. Likewise, traditional monoculture systems have aided in identifying biomarkers of susceptibility to inhaled toxicants and served as a screening platform for safety assessment of pulmonary toxicants. Despite their contributions, and classic models have not been able to accurately represent the heterogeneity of the human population and account for interindividual variability in response to inhaled toxicants and susceptibility to the adverse health effects. Development of new technologies that can investigate genetic predisposition, are cost and time efficient, and are ethically sound, will enhance elucidation of mechanisms of inhalation toxicity, and aid in the development of novel pharmaceuticals and/or safety evaluation. This review will describe the classic and novel cell-based inhalation toxicity models and how these emerging technologies can be incorporated into regulatory or nonregulatory testing to address interindividual variability and improve overall human health.
仅空气污染每年就导致700万人死亡，显然，吸入有毒物质暴露的不良影响在21世纪仍然是一个主要的公共卫生问题。空气污染物对人类健康影响的评估和特征描述源于流行病学和临床研究，这些研究将室外和室内空气污染物暴露与不良的肺部和心血管健康结果联系起来。动物模型研究支持了流行病学研究结果，并且在确定吸入暴露后环境化学物质对认知能力、肝脏疾病和代谢功能障碍的全身影响方面起到了关键作用。同样，传统的单一培养系统有助于识别对吸入有毒物质易感性的生物标志物，并作为肺部有毒物质安全性评估的筛选平台。尽管它们做出了贡献，但经典模型仍无法准确代表人类群体的异质性，也无法解释个体对吸入有毒物质的反应差异以及对不良健康影响的易感性。开发能够研究遗传易感性、具有成本效益和时间效益且符合伦理道德的新技术，将有助于阐明吸入毒性机制，并有助于开发新型药物和/或进行安全性评估。本综述将描述基于细胞的经典和新型吸入毒性模型，以及如何将这些新兴技术纳入监管或非监管测试，以解决个体差异问题并改善整体人类健康。
