Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Evaluation of the Tobacco Heating System 2.2. Part 3: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects for modified risk tobacco product, THS 2.2      
dateReleased:
10-03-2016
description:
The objective of the study was to characterize the toxicity due to sub-chronic inhalation of test atmospheres from the heat not burn modified risk tobacco product (MRTP) - Tobacco Heating System version 2.2 (THS2.2) and to compare it to the toxicity inherent to the inhalation of mainstream smoke (MS) from the Reference Cigarette 3R4F (University_of_Kentucky, 2003). The 90-day nose-only inhalation study on Sprague-Dawley rats was performed according to the Organization for Economic Co-operation and Development (OECD) Test Guideline 413 (OECD, 2009), with special emphasis on histopathology of the respiratory tract, lung inflammation and additional systems toxicology-based assessment using transcriptomics. Animals were exposed to mainstream smoke from 3R4F reference cigarettes or THS2.2 mainstream aerosol at 3 target nicotine concentrations. The exposure regimen consisted of 6 hours a day, 5 days per week for 13 weeks, followed by 42 days recovery period. Exposure-related changes such as increased blood neutrophil count, decreased blood lymphocyte count, increased activity of alkaline phosphatase in serum and decreased cholesterol and glucose in serum were observed in 3R4F and THS2.2 exposed animals. Reduction in respiratory minute volume was significantly less pronounced in THS2.2 as compared to 3R4F-exposed groups. Histopathological findings in the respiratory tract including epithelial cell hyperplasia, squamous metaplasia, atrophy and accumulation of pigmented alveolar macrophages were significantly lower in THS2.2 than in 3R4F exposed groups. The degree of lung inflammation as indicated by accumulation of immune cells and pro-inflammatory and chemotactic cytokines in bronchioalveolar lavage fluid were significantly lower in THS2.2 as compared to 3R4F exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent gene expression changes following 3R4F exposure that were much less pronounced in the THS2.2-exposed groups. In summary, the data indicates that the aerosol from THS2.2 did not cause additional toxicity as compared to the smoke from the 3R4F conventional cigarette. The toxicity on respiratory tract organs in THS2.2 exposed animals was much lower than in the rats exposed to 3R4F reference cigarette. Overall, the changes observed following exposure to THS2.2 can be considered mild and are very similar to previously published effects caused by nicotine only exposure at similar test atmosphere concentrations.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-4492
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-4492/E-MTAB-4492.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-4492/E-MTAB-4492.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

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.