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述评:评估肺癌风险的大鼠慢性吸入研究可能比其名声更好。

Commentary: the chronic inhalation study in rats for assessing lung cancer risk may be better than its reputation.

机构信息

National Research Centre for the Working Environment, Copenhagen, Denmark.

出版信息

Part Fibre Toxicol. 2019 Nov 21;16(1):44. doi: 10.1186/s12989-019-0330-4.

Abstract

Recently, Borm and Driscoll published a commentary discussing grouping of Poorly Soluble particles of Low Toxicity (PSLTs) and the use of rats as an animal model for human hazard assessment of PSLTs (Particle and Fibre Toxicology (2019) 16(1):11). The commentary was based on the scientific opinion of several international experts on these topics. The general conclusion from the authors was a cautious approach towards using chronic inhalation studies in rats for human hazard assessment of PSLTs. This was based on evidence of inhibition of particle clearance leading to overload in the rats after high dose exposure, and a suggested over reactivity of rat lung cancer responses compared to human risk.As a response to the commentary, we here discuss evidence from the scientific literature showing that a) diesel exhaust particles, carbon black nanoparticles and TiO nanoparticles have similar carcinogenic potential in rats, and induce lung cancer at air concentrations below the air concentrations that inhibit particle clearance in rats, and b) chronic inhalation studies of diesel exhaust particles are less sensitive than epidemiological studies, leading to higher risk estimates for lung cancer. Thus, evidence suggests that the chronic inhalation study in rats can be used for assessing lung cancer risk insoluble nanomaterials.

摘要

最近,Borm 和 Driscoll 发表了一篇评论,讨论了低毒性难溶性颗粒(PSLTs)的分组以及将大鼠用作评估 PSLTs 对人类危害的动物模型的问题(Particle and Fibre Toxicology(2019)16(1):11)。该评论基于几位国际专家在这些主题上的科学意见。作者的总体结论是,在使用大鼠进行慢性吸入研究以评估 PSLTs 对人类的危害时,应采取谨慎的方法。这是基于高剂量暴露后导致大鼠颗粒清除抑制和过载的证据,以及与人类风险相比,大鼠肺癌反应的过度反应。作为对评论的回应,我们在这里讨论了来自科学文献的证据,表明:a)柴油机排气颗粒、碳纳米黑颗粒和 TiO 纳米颗粒在大鼠中有相似的致癌潜力,并在低于抑制大鼠颗粒清除的空气浓度下诱导肺癌;b)柴油机排气颗粒的慢性吸入研究不如流行病学研究敏感,导致肺癌风险估计值更高。因此,有证据表明,大鼠慢性吸入研究可用于评估难溶性纳米材料的肺癌风险。

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