Erythritol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Safety assessment of inhaled xylitol in mice and healthy volunteers

Author:

Lakshmi Durairaj, Janice Launspach, Janet L Watt, Thomas R Businga, Joel N Kline, Peter S Thorne and Joseph Zabner

Year:

2004

Bibliographic source:

Respiratory Research 2004, 5 :13 doi:10.1186/1465-9921-5-1

Report date:

2004

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Test of the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers

GLP compliance:

not specified

Test type:

other: in vivo and clinical study by inhalation

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:

D-erythro-pentitol

Specific details on test material used for the study:

purity not specified, 5% solution in water and NaCl

Test animals

Species:

mouse

Strain:

C57BL

Sex:

not specified

Details on test animals or test system and environmental conditions:

Clinical study as well: ten subjects who underwent graded exposure to aerosolized xylitol as a part of the pilot study. Mean age was 29.1 yrs, and equal numbers of males and females were studied

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: water saline salution

Mass median aerodynamic diameter (MMAD):

ca. 0.82 µm

Geometric standard deviation (GSD):

ca. 1.46

Details on inhalation exposure:

150 minutes

Duration of exposure:

ca. 150 min

Concentrations:

5% in saline solution

No. of animals per sex per dose:

6

Control animals:

yes

Results and discussion

Effect levels

Key result

Sex:

not specified

Dose descriptor:

other: NOEC

Effect level:

ca. 5 other: %

Based on:

test mat. (dissolved fraction)

Exp. duration:

150 min

Mortality:

no

Clinical signs:

other: no

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

Interpretation of results:

GHS criteria not met

Conclusions:

Aerosolized xylitol was well tolerated by naïve and hypersensitive in mice with no significant effects on the airway physiology or composition of airway inflammatory cells. Results were further confirmed in healthy human volunteers.

Executive summary:

Aerosolized xylitol was well tolerated by naïve and hypersensitive  in mice   with   no   significant   effects   on   the   airway physiology or composition of airway inflammatory cells. Results were further confirmed in healthy human volunteers.