Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
Xylitol was not genetically active in bacterial or animal cells in vitro or in animals in vivo.
Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
no positive controls
GLP compliance:
not specified
Type of assay:
micronucleus assay
Species:
mouse
Strain:
other: Fullinsdorf albino (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
Three males (average weight about 38 g) and three females (average weight about 33 g)
Route of administration:
oral: gavage
Vehicle:
dissolved in PBS
Duration of treatment / exposure:
treated twice, 30 and 6 hours before sacrifice
Frequency of treatment:
two times
Post exposure period:
treated twice, 30 and 6 hours before sacrifice
Remarks:
Doses / Concentrations:
0, 1820, 3280 and 5333 mg/kg/body weight
Basis:
actual ingested
No. of animals per sex per dose:
3 males and 3 females per dose group
Control animals:
not specified
Positive control(s):
no data
Tissues and cell types examined:
Smears of the bone marrow of both femora were prepared and stained as described by. 4000 erythrocytes per animal were checked for micronuclei.
Statistics:
The statistical analysis was performed by means of the Student-t-test.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
not specified

After two fold application of the test substance (doses up to 5333 mg/kg) no significant increase of micronuclei containing erythrocytes could be shown in the bone marrow of Füllinsdorf Albino mice of either sex.

Conclusions:
Interpretation of results (migrated information): negative

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
The test substance caused no observable mutagenic effect in the system studied.
Executive summary:

The micronucleus test in the mouse was carried out to assess potential mutagenic activity of the tests substance. Three male and three female mice were used per dosage group. They were treated twice, 30 and 6 hours before sacrifice, with up to 5333 mg/kg of the test substance dissolved in PBS. Erythrocytes were checked for micronuclei.

After twofold applications, no significant increase of micronuclei containing erythrocytes could be shown in the bone marrow of Füllinsdorf Albino mice of either sex. Therefore, the test substance causes neither chromosome breaks nor mitotic non-disjunction in the bone marrow of the mouse.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

The test substance was concluded to be negative in the Ames test with the Salmonella typhimurium strains TA 1535, TA 1537, and TA 1538. No indications of mutagenicity were observed at any dose level in either TA 1535 or 1537 when tested up to 125 mg/plate (i.e., 125,000 ug/plate) in the absence or presence of S9. In strain TA 1538, a statistically significant not reproducible approximately twofold increase in the number of revertants was observed at 125 mg/plate, but considered to be an artefact and not indicative of a positive mutagenicity result. The assay was conducted prior of the 1997 adaptation of the OECD 471, and was conducted with up to a 25-fold higher top dose concentration than recommended by OECD. It was also conducted with a battery of tester strains that included only TA 1535 and TA 1537 of the currently recommended five tester strains. However, strains TA 98 and TA 1538, and TA 100 and TA 1535 are isogenic. Considering this, and the high dose levels used, it is highly unlikely that the use of strains TA 98 and TA 100 would have changed the outcome of the assay. Furthermore, the assay did not include an E.coli WP2 or S. typhimurium TA 102 tester strain. These strains are known to specifically detect certain oxidizing mutagens, cross-linking agents and hydrazines other Salmonella tester strains may not be sensitive to. Based on the physico-chemical characteristics of the test substance, the inclusion of any of these strains would not have changed the outcome of the Ames assay. In addition, there was no indication of in vitro or in vivo mutagenicity for any other genetic toxicology endpoint.


Justification for selection of genetic toxicity endpoint
In addition to the study selected above, an Ames assay and mouse lymphoma assay are pertinent to the hazard conclusion for this endpoint.

Justification for classification or non-classification

The test substance did not produce mutagenicity in vitro or clastogenicity when evaluated in vitro and in laboratory animals. Based on an assessment of the robust genetic toxicity data for this substance, the substance does not need to be classified for germ-cell mutagenicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.