Xylitol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Xylitol

EC Number:

201-788-0

EC Name:

Xylitol

Cas Number:

87-99-0

Molecular formula:

C5H12O5

IUPAC Name:

(2R,3r,4S)-pentane-1,2,3,4,5-pentol

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:

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

Remarks on result:

other:

Remarks:

No significant increase in enhanced respiratory pause and no change in airway cellular response. Inhalation of aerosolized iso-osmotic test substance was well-tolerated by naïve and atopic mice.

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