E-MTAB-5910 - Toxicity of the main electronic cigarette components, propylene glycol, glycerin and nicotine in Sprague Dawley rats in a 90-day OECD inhalation study complemented with molecular endpoints (RNE)
Last updated on 31 October 2017, released on 3 November 2017
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 1.520mg PG/L + 1.890mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.7mg/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.
transcription profiling by array, disease state design, in Vivo
Toxicity of the main electronic cigarette components, propylene glycol, glycerin and nicotine in Sprague Dawley rats in a 90-day OECD inhalation study complemented with molecular endpoints (RNE). Phillips B, Titz B, Kogel U, Sharma D, Leroy P, Xiang Y, Vuillaume G, Lebrun S, Sciuscio D, Ho J, Nury C, Guedj E, Elamin A, Esposito M, Krishnan S, Schlage WK, Veljkovic E, Ivanov NV, Martin F, Peitsch MC, Hoeng J, Vanscheeuwijck P. , PMID:28882640