Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Safety assessment of inhaled xylitol in mice and healthy volunteers
Author:
Durairaj L, Launspach J, Watt JL, Businga TR, Kline JN, Thorne PS and Zabner J
Year:
2004
Bibliographic source:
Respiratory Research 2004, 5:13

Materials and methods

Principles of method if other than guideline:
The safety and tolerability of aerosolized iso-osmotic test substance was tested in mice
GLP compliance:
no
Test type:
other: The safety and tolerability of aerosolized iso-osmotic test substance was tested in mice
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: not reported

Test animals

Species:
mouse
Strain:
other: C57Bl/6
Sex:
not specified

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: water
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
150 min
Concentrations:
5% solution in water
No. of animals per sex per dose:
6
Control animals:
yes

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
other: NOEC
Effect level:
5 other: %
Based on:
test mat.
Exp. duration:
150 min

Any other information on results incl. tables

In naïve mice, methacholine responsiveness was unchanged after exposures to the test substance compared to inhaled saline (p = 0.49). There was no significant increase in enhanced respiratory pause in antigen-challenged mice after test substance exposure (p = 0.38). There was no change in airway cellular response after test substance exposure in naïve and antigen-challenged mice.

Applicant's summary and conclusion

Conclusions:
Inhalation of aerosolized iso-osmotic test substance was well-tolerated by naïve and atopic mice
Executive summary:

This was a prospective cohort study of C57B1/6 mice in an animal laboratory at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline (control) or the test substance (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and test substance exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Mice were evaluated for bronchial hyperreactivity to inhaled methacholine (using the Buxco whole body plethysmography system) before and after the exposures; other mice were monitored periodically during exposure by whole body plethysmography. All mice underwent whole lung lavage the next day for cell count and differential.

In naïve mice, methacholine responsiveness was unchanged after exposures to the test substance compared to inhaled saline (p = 0.49). There was no significant increase in enhanced respiratory pause in antigen-challenged mice after test substance exposure (p = 0.38). There was no change in airway cellular response after test substance exposure in naïve and antigen-challenged mice.

Inhalation of aerosolized iso-osmotic test substance was well-tolerated by naïve and atopic mice