Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2018-03-13 , DOI: 10.1016/j.fct.2018.02.058 Bjoern Titz , Ulrike Kogel , Florian Martin , Walter K. Schlage , Yang Xiang , Catherine Nury , Sophie Dijon , Karine Baumer , Dariusz Peric , David Bornand , Remi Dulize , Blaine Phillips , Patrice Leroy , Gregory Vuillaume , Stefan Lebrun , Ashraf Elamin , Emmanuel Guedj , Keyur Trivedi , Nikolai V. Ivanov , Patrick Vanscheeuwijck , Manuel C. Peitsch , Julia Hoeng
Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. Here, we report the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Transcriptomics, proteomics, and lipidomics analyses complemented the standard endpoints. In the respiratory nasal epithelium, CS induced an adaptive tissue and inflammatory response, which was much weaker after CHTP1.2 aerosol exposure, mostly limited to the highest CHTP1.2 concentration (at twice the 3R4F CS concentration: 50 vs. 23 μg nicotine/L), in female rats. In the lungs, the effects of CS exposure included inflammatory and cellular stress responses, which were absent or much lower after CHTP1.2 aerosol exposure. Outside of the respiratory tract, CS and CHTP1.2 aerosol induced effects that were previously associated with exposure to any nicotine-containing aerosol, e.g., lower lipid concentrations in serum. Overall, this systems toxicology analysis complements and confirms the results from classical toxicological endpoints and further suggests potentially reduced respiratory health risks of CHTP1.2.
中文翻译:
一项为期90天的OECD TG 413大鼠吸入研究(具有系统毒理学终点)表明,与香烟烟雾相比,碳加热的1.2版碳烟产品(CHTP1.2)的气雾剂的暴露效应降低。二。系统毒理学评估
改良风险烟草产品(MRTP)具有降低与吸烟有关的健康风险的潜力。碳加热烟草产品1.2(CHTP1.2)是一种潜在的MRTP,它使用压缩碳热源通过加热烟草来产生气溶胶。在这里,我们报告了一项为期90天的大鼠吸入研究(经合组织测试指南413)的系统毒理学部门的结果,以评估CHTP1.2气雾剂与香烟烟雾(CS)的影响。转录组学,蛋白质组学和脂质组学分析补充了标准终点。在呼吸道鼻上皮中,CS诱导了适应性组织和炎症反应,在CHTP1.2气雾剂暴露后,这种反应要弱得多,主要限于最高CHTP1.2浓度(两倍于3R4F CS浓度:50 vs. 23μg尼古丁/ L),在雌性大鼠中。在肺里 CS暴露的影响包括炎性反应和细胞应激反应,在CHTP1.2气溶胶暴露后这些反应不存在或更低。在呼吸道之外,CS和CHTP1.2气雾剂诱发的效应以前与暴露于任何含尼古丁的气溶胶有关,例如,血清中较低的脂质浓度。总体而言,该系统毒理学分析补充并证实了经典毒理学终点的结果,并进一步暗示了CHTP1.2可能降低呼吸道健康风险。