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An E-cigarette Aerosol Generation, Animal Exposure and Toxicants Quantification System to Characterize in vivo Nicotine Kinetics in Arterial and Venous Blood

Jushan Zhang, Mo Xue*, Rong Pan, Yujie Zhu, Zhongyang Zhang, Haoxiang Cheng, Johan L M Bjorkegren, Jia Chen6, Zhiqiang Shi*, Ke Hao*

The increasing e-cigarette use worldwide presents an urgent need to characterize their nicotine delivery property, brain stimulation and potential long-term health effects. We constructed an end-to-end system enabling combustible- cigarette (c-cigarette) and e-cigarette aerosol generation, animal exposure, and effect assessment. The system consists of (1) a 10-channel aerosol generator resembling human smoking/vaping scenarios, (2) nose-only and whole- body exposure chambers suitable for long or short-duration studies, (3) a lab protocol for animal exposure and collecting arterial and venous blood <1 minute after the exposure, and (4) chromatograph and mass spectrometry to quantify nicotine concentrations in aerosol and biospecimens. We applied the system in a proof-of-principle study characterizing in vivo nicotine delivery after e-cigarette aerosol inhalation. Groups of Sprague-Dawley rats were exposed to e-cigarette aerosols for 1, 2 and 4 minutes, respectively. Arterial and venous blood samples were collected immediately after the exposure. We also directly compared nose-only and whole-body exposure approaches. After nose-only e-cigarette aerosol exposure, the nicotine concentration in arterial blood was substantially higher (11.32 ng/ mL in average) than in veins. Similar arterio-venous concentration difference was observed in whole-body exposure experiments. In summary, we described a complete system ideal for e- and c-cigarette in vivo nicotine kinetics and long-term health research. Our findings highlight arterial blood as the suitable bio-specimen for e-cigarette nicotine delivery studies.