Xylitol

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

supporting study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

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

Reason / purpose for cross-reference:

reference to same study

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

Species:

mouse

Strain:

other: C57Bl/6

Sex:

not specified

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

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.

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.

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

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, 5:13

Materials and methods

Study type:

other: The safety and tolerability of aerosolized iso-osmotic test substance was tested in humans

Principles of method if other than guideline:

The safety and tolerability of aerosolized iso-osmotic test substance was tested in humans.

GLP compliance:

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

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

- Purity: not reported

Method

Details on study design:

- Subjects: Human (male/female)
- Aerosol nose only
- Vehicle: water
- Analytical verification of test atmosphere concentrations performed
- Duration of exposure: 49 minutes
- Volume: 1,5, and 10 mL of 5% solution in water
- 10 subjects received 1-10 mL sequentially; 11 subjects received only 10 mL

Results and discussion

Results:

LOEC (male/female) = 10 mL based on test material (49-minute exp. duration)

Any other information on results incl. tables

In normal volunteers, there was no change in Forced Expiratory Volume in 1 second (FEV1) after test substance exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 mL test substance exposure, which promptly resolved after exposure completion. Bronchoalveolar lavage (BAL) cytokine levels were below the detection limits after xylitol exposure in normal volunteers.

Applicant's summary and conclusion

Conclusions:

Inhalation of aerosolized iso-osmotic test substance was well-tolerated by healthy human volunteers.

Executive summary:

This was a prospective cohort study of healthy human volunteers at the clinical research center of a university hospital. Normal human volunteers underwent exposures to aerosolized saline (10 mL) and the test substance, with spirometry performed at baseline and after inhalation of 1, 5, and 10 mL. Serum osmolality and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized test substance exposure for levels of inflammatory markers.

In normal volunteers, there was no change in Forced Expiratory Volume in 1 second (FEV1) after test substance exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 mL test substance exposure, which promptly resolved after exposure completion. Bronchoalveolar lavage (BAL) cytokine levels were below the detection limits after xylitol exposure in normal volunteers. Inhalation of aerosolized iso-osmotic the test substance was well-tolerated by healthy human volunteers.