PXD005958

PXD005958 is an original dataset announced via ProteomeXchange.

Title	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 [LIVER DATA]
Description	The main constituents of electronic cigarette liquids are nicotine, propylene glycol (PG), and vegetable glycerin (VG), together with distilled water and flavors. To assess the toxicity of PG/VG mixtures with and without nicotine as basic components of liquids used in e-cigarettes, a 90-day rat inhalation study according to the Organization for Economic Co-operation and Development test guideline 413 was conducted. Sprague-Dawley (SD) rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, or nebulized vehicle (saline), or three concentrations of PG/VG (0.174 mg PG/l + 0.210 mg VG/l; 0.520 mg PG/l + 0.630 mg VG/l; 1.520 mg PG/l + 1.890 mg VG/l) – with (test item) and without (reference item) 23 µg nicotine/L. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared to vehicle exposure, the tested PG/VG aerosols showed only very limited biological effects with no signs of toxicity, both for the standard toxicological endpoints (e.g., histopathology, clinical chemistry) and the systems toxicological analyses (transcriptomics, proteomics, and lipidomics). The addition of nicotine to the PG/VG aerosols (23 µg/l) resulted in effects in line with nicotine effects in previous studies. These included up-regulation of xenobiotic enzymes (Cyp1a1 and Fmo3) in the lung and metabolic effects, e.g., reduction in serum lipid concentrations and changes in the expression of metabolic enzymes in the liver. Signs of a generalized stress response to nicotine exposure such as decreased thymus weights were observed; and likely, a subset of the observed metabolic alterations was interlinked with this generalized stress response. Under the conditions of this 90-day SD rat inhalation study, no toxicologically relevant effects of PG/VG aerosols (up to 1.520 mg PG/l + 1.890 mg VG/l) were observed, and the no observed adverse effect level (NOAEL) for PG/VG/nicotine was determined to be 438/544/6.7 mg/kg/day. Further the study demonstrated how complementary systems toxicology analyses can reveal, also in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.
HostingRepository	PRIDE
AnnounceDate	2017-09-13
AnnouncementXML	Submission_2017-09-13_04:25:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bjoern Titz
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	methylthiolated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-23 03:06:04	ID requested
⏵ 1	2017-09-13 04:25:05	announced

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, 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. Food Chem Toxicol, 109(Pt 1):315-332(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: rat, electronic cigarette, lung

Julia Hoeng
contact affiliation	Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland (part of Philip Morris International group of companies)
contact email	julia.hoeng@pmi.com
lab head
Bjoern Titz
contact affiliation	Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
contact email	bjorn.titz@pmi.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005958
     1. Label: PRIDE project
     2. Name: 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 [LIVER DATA]