A Newly Developed Aerosol Exposure Apparatus for Heated Tobacco Products for In Vivo Experiments Can Deliver Both Particles and Gas Phase With High Recovery and Depicts the Time-Dependent Variation in Nicotine Metabolites in Mouse Urine
A Newly Developed Aerosol Exposure Apparatus for Heated Tobacco Products for In Vivo Experiments Can Deliver Both Particles and Gas Phase With High Recovery and Depicts the Time-Dependent Variation in Nicotine Metabolites in Mouse Urine
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DOI：
10.1093/ntr/ntab123
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发表时间：
2021-06-10
影响因子：
4.7
通讯作者：
Ishii, Kazuyuki
中科院分区：
文献类型：
--
作者：
Sawa, Marie;Ushiyama, Akira;Ishii, Kazuyuki
简介：没有标准化的气溶胶暴露装置来输送加热的烟草制品（HTPs）用于体内实验。因此，我们开发了一种新的HTPs气溶胶暴露装置的小鼠，并证明，尼古丁和其他化学物质的HTPs气溶胶所产生的装置可以传递到小鼠复制human smoke.Aims和方法：尼古丁，焦油，和一氧化碳（CO）的量IQOS（万宝路常规热棒）气溶胶产生的两种类型的设备进行了测定。将C57 BL/6N小鼠暴露于IQOS气雾剂，然后测定尿尼古丁代谢产物。此外，监测小鼠的皮肤表面温度以确认尼古丁的血管收缩作用。HTPs新型空气推入式吸入装置（APIA）的IQOS气雾剂中的化学品量与分析型蒸汽烟机（LM4E）相当（尼古丁中1.60 +/-0.08 [APIA] vs. 1.46 +/-0.07 mg/支[LM4E]，CO中0.55 +/-0.04 [APIA] vs. 0.45 +/-0.01 mg/支[LM4E]）。通过APIA将小鼠暴露于IQOS气雾剂后，测定尿尼古丁代谢物水平;暴露后1小时可替宁和3-羟基可替宁（3-HC）的峰值分别为6.82 μ g/mg肌酐，暴露后2小时为32.9 μ g/mg肌酐。皮肤表面温度下降，并在30分钟时低于（33.5摄氏度+/-0.5摄氏度）比前曝光（37.6摄氏度+/-0.8摄氏度）。结论：新的装置HTPs气溶胶暴露于小鼠表现出良好的性能，在收集的气溶胶的化学分析和尿中尼古丁代谢物的波动。
Introduction: There is no standardized aerosol exposure apparatus to deliver heated tobacco products (HTPs) for in vivo experiments. Therefore, we developed a novel HTPs aerosol exposure apparatus for mice and demonstrated that nicotine and other chemicals in HTPs aerosol generated by the apparatus can be delivered to mice which replicate human smoke.Aims and Methods: The amounts of nicotine, tar, and carbon monoxide (CO) in IQOS (Marlboro Regular HeatSticks) aerosol generated by two types of apparatuses were determined. C57BL/6N mice were exposed to IQOS aerosol, followed by determination of the urinary nicotine metabolites. Further, the skin surface temperature of mice was monitored to confirm the vasoconstriction action of nicotine.Results: The amount of chemicals in IQOS aerosol by the novel air push-in inhalation apparatus for HTPs (APIA) was equivalent to that of the analytical vaping machine (LM4E) (1.60 +/- 0.08 [APIA] vs. 1.46 +/- 0.07 mg/stick [LM4E] in nicotine and 0.55 +/- 0.04 [APIA] vs. 0.45 +/- 0.01 mg/stick [LM4E] in CO). After mice were exposed to IQOS aerosol by APIA, the urinary nicotine metabolite levels were determined; peak values in cotinine and 3-hydroxycotinine (3-HC) were 6.82 mu g/mg creatinine at 1 hour after exposure and 32.9 mu g/mg creatinine at 2 hours after exposure, respectively. The skin surface temperature decreased and was lower (33.5 degrees C +/- 0.5 degrees C) at 30 minutes than before exposure (37.6 degrees C +/- 0.8 degrees C).Conclusions: The new apparatus for HTPs aerosol exposure to mice showed good performances in terms of both chemical analysis of collected aerosol and fluctuations in the urinary nicotine metabolites.