Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.

中文翻译：

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内源性并不总是意味着无害：通过吸入对铁毒性的范围界定。

环境空气污染是全球疾病负担的主要风险因素。颗粒物（PM）引起的毒性的一种可能途径是通过铁（Fe），这是大气中最丰富的金属。综述的目的是考虑吸入性接触后Fe介导的毒性的复杂性，重点是作为过渡金属的Fe的化学和表面反应性，以及通过活性氧（ROS）产生的毒性的可能途径以及对尺寸的考虑，PM的形态和来源。对4个数据库进行的广泛搜索确定了2189篇期刊文章和报告，这些文章检查了过去10年中通过吸入对铁的暴露情况。这些按标题顺序分析，摘要和全文，以鉴定87篇有关吸入或滴入呼吸系统的含铁PM毒性的发表结果的文章。其余87篇论文进行了综述，以总结涉及吸入或滴注后含PM或Fe或铁氧化物的体外，体内和流行病学研究的研究。这些调查的主要发现已汇总并制成表格。流行病学研究表明，接触氧化铁与癌症，心血管疾病和几种呼吸道疾病的发病率增加相关。发现铁PM在体外和体内均可引起炎症作用，并在吸入后易位至包括大脑在内的较远位置。通过吸入产生含PM的铁介导的毒性的潜在途径是通过产生ROS，导致脂质过氧化以及DNA和蛋白质氧化。我们的建议包括扩大流行病学，体内和体外研究，整合本综述中概述的研究改进，例如颗粒制备方法，细胞系类型和动物模型，以加深我们对这些方法之间复杂的生物学相互作用的了解粒子。