Registration Dossier

Administrative data

Endpoint:
health surveillance data
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

Study type:
other:
Endpoint addressed:
acute toxicity: inhalation
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

Reference
Name:
Unnamed
Type:
Constituent
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
- Control animals were used

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. Bronchoaveolar 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.