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Title: Systems toxicological assessment of a mentholated heat-not-burn modified risk tobacco product in a 90-day OECD 413 rat inhalation study demonstrates reduced exposure effects and provides mechanistic insights      
dateReleased:
10-03-2016
description:
Toward the reduction of smoking-related health risks potential reduced risk products (pRRPs) are being developed. The Tobacco Heating System (THS) 2.2 is a recently developed pRRP, which relies on the heat-not-burn principle. We present results from the systems-toxicology arm of a 90-day Organization for Economic Co-operation and Development test guideline 413 inhalation study for the assessment of a mentholated version of THS2.2 (THS2.2M). Sprague-Dawley rats were nose-only exposed, 6?h/day, 5 days/week to filtered air, three concentrations of THS2.2M aerosol (15μg/l, 23μg/l, 50μg/l nicotine), cigarette smoke (CS) from the reference cigarette 3R4F (23μg/l nicotine), or CS from reference cigarettes with two different menthol concentrations (23μg/l nicotine; 1.2 and 2.4 mg menthol/cigarette). Reversibility of the exposure effects was assessed in a subset of the groups following 42 days of filtered air exposure. Standard toxicology endpoints were complemented by transcriptomics and quantitative proteomics analyses of nasal epithelium and lung tissue and by lipidomics analysis of lung tissue. The adaptive response of the nasal epithelium to CS exposure included squamous cell metaplasia and an inflammatory response, with high correspondence between the molecular and histopathological results. In contrast to CS exposure, the adaptive tissue and molecular changes to THS2.2M aerosol exposure were much reduced and mostly limited to the highest THS2.2M concentration in female rats. In the lung, CS exposure induced an inflammatory response, triggered cellular stress responses (e.g., oxidative stress and xenobiotic metabolism), and affected sphingolipid metabolism. These responses were not observed or much lower upon THS2.2M aerosol exposure. All in all, this system toxicology analysis complements and reconfirms the classical toxicological endpoints and further suggests a potentially reduced risk of THS2.2M.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-4493
refinement:
raw
keywords:
functional genomics
dateModified:
08-05-2016
availability:
available
types:
gene expression
name:
Rattus norvegicus
ID:
A-AFFY-43
name:
Affymetrix GeneChip Rat Genome 230 2.0 [Rat230_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-4493/E-MTAB-4493.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-4493/E-MTAB-4493.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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