Evaluation of toxicity of aerosols from flavored e-liquids in Sprague-Dawley rats in a 90-day OECD inhalation study, complemented by transcriptomics analysis.
Animals
Biomarkers
/ blood
Consumer Product Safety
E-Cigarette Vapor
/ toxicity
Electronic Nicotine Delivery Systems
Female
Flavoring Agents
/ toxicity
Gene Expression Profiling
Inhalation Exposure
Liver
/ drug effects
Male
Rats, Sprague-Dawley
Respiratory System
/ drug effects
Risk Assessment
Time Factors
Toxicity Tests
Transcriptome
/ drug effects
Vaping
/ adverse effects
E-liquid
Flavor
Inhalation toxicology
OECD
System toxicology
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
15
02
2020
accepted:
22
04
2020
pubmed:
6
5
2020
medline:
13
7
2021
entrez:
6
5
2020
Statut:
ppublish
Résumé
The use of flavoring substances is an important element in the development of reduced-risk products for adult smokers to increase product acceptance and encourage switching from cigarettes. In a first step towards characterizing the sub-chronic inhalation toxicity of neat flavoring substances, a study was conducted using a mixture of the substances in a base solution of e-liquid, where the standard toxicological endpoints of the nebulized aerosols were supplemented with transcriptomics analysis. The flavor mixture was produced by grouping 178 flavors into 26 distinct chemical groups based on structural similarities and potential metabolic and biological effects. Flavoring substances predicted to show the highest toxicological effect from each group were selected as the flavor group representatives (FGR). Following Organization for Economic Cooperation and Development Testing Guideline 413, rats were exposed to three concentrations of the FGR mixture in an e-liquid composed of nicotine (23 µg/L), propylene glycol (1520 µg/L), and vegetable glycerin (1890 µg/L), while non-flavored and no-nicotine mixtures were included as references to identify potential additive or synergistic effects between nicotine and the flavoring substances. The results indicated that the inhalation of an e-liquid containing the mixture of FGRs caused very minimal local and systemic toxic effects. In particular, there were no remarkable clinical (in-life) observations in flavored e-liquid-exposed rats. The biological effects related to exposure to the mixture of neat FGRs were limited and mainly nicotine-mediated, including changes in hematological and blood chemistry parameters and organ weight. These results indicate no significant additive biological changes following inhalation exposure to the nebulized FGR mixture above the nicotine effects measured in this sub-chronic inhalation study. In a subsequent study, e-liquids with FGR mixtures will be aerosolized by thermal treatment and assessed for toxicity.
Identifiants
pubmed: 32367274
doi: 10.1007/s00204-020-02759-6
pii: 10.1007/s00204-020-02759-6
pmc: PMC7303093
doi:
Substances chimiques
Biomarkers
0
E-Cigarette Vapor
0
Flavoring Agents
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2179-2206Références
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