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Food Chem Toxicol. 2017 Nov;109(Pt 1):315-332. doi: 10.1016/j.fct.2017.09.001. Epub 2017 Sep 5.

Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints.

Author information

1
Philip Morris International Research Laboratories Pte. Ltd. (part of Philip Morris International Group of Companies), 50 Science Park Road, Singapore 117406, Singapore.
2
Philip Morris International Research and Development (part of Philip Morris International Group of Companies), Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland.
3
Biology Consultant, Max-Baermann-Str. 21, 51429 Bergisch Gladbach, Germany.
4
Philip Morris International Research and Development (part of Philip Morris International Group of Companies), Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland. Electronic address: Patrick.vanscheeuwijck@pmi.com.

Abstract

While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared with vehicle exposure, the PG/VG aerosols showed only very limited biological effects with no signs of toxicity. Addition of nicotine to the PG/VG aerosols resulted in effects in line with nicotine effects observed in previous studies, including up-regulation of xenobiotic enzymes (Cyp1a1/Fmo3) in the lung and metabolic effects, such as reduced serum lipid concentrations and expression changes of hepatic metabolic enzymes. No toxicologically relevant effects of PG/VG aerosols (up to 1.520  mg PG/L + 1.890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.6 mg/kg/day. This study demonstrates how complementary systems toxicology analyses can reveal, even in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.

KEYWORDS:

Electronic cigarette; Glycerin; Inhalation toxicity; Nicotine; Organization for Economic Cooperation and Development (OECD) 413 guideline; Propylene glycol; Systems toxicology

PMID:
28882640
DOI:
10.1016/j.fct.2017.09.001
[Indexed for MEDLINE]
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