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Key value for chemical safety assessment

Genetic toxicity in vivo

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
not specified
GLP compliance:
yes
Type of assay:
micronucleus assay
Species:
mouse
Strain:
other: OF-1 albino mice
Sex:
male/female
Details on test animals and environmental conditions:
Weight: male/female 25g
Supplier: from a SPF colny IFFA-CREDO, L'Arbresie France
Quarantine period of 1 week, the animals were allowed a libitum access to food (Aliment Rats-Souris Charles River, produced by U.A.R, Villemoisson/Orge France) and drinking water.
Animals were housed 5 of the same sex per cage in Makrolon type III cages.
Route of administration:
oral: gavage
Vehicle:
deionised water
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Control
Dose / conc.:
1 500 mg/kg bw/day (nominal)
Remarks:
Doses / Concentrations:
1500 mg/kg bw
No. of animals per sex per dose:
5 mice / sex / Group
Control animals:
yes, concurrent vehicle
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
At low magnification of the microscope no neticeable differences in bone marros nucleated cells were observed between tested animals and negative control.
In the positive control group (Thio-TEPA) decreased numbers of nucleated bone marrow cells were noted.

There was no statistically significant increase in the number of micronucleated polychromatic erythrocytes in animals exposed to 500 mg/kg of the tested substance compared to negative controls. In animals treated with positive control there was a statistically significant increased number of micronucleated cells.
The ration of polychromatic to normochromatic erythrocytes was markedly decreased in mice treated with positive control. There is no difference between animals treated with the tested substance and the negative control for this ratio.
Conclusions:
In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test article did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse. Therefore the tested substance is considered to be non-mutagenic in this micronucleus assay.
Executive summary:

The tested substance is considered to be non-mutagenic in this micronucleus assay.

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

Additional information

Both in vitro and in vivo mutagenicity tests are available for the tested substance.

The results of the in vitro ames and in vitro chromosome aberration test, made are both negative.

In addiction also the in vivo micronucleus (bone marrow) test showed negative results.

Based on these tests, the tested substance could be considered as not mutagenic.


Short description of key information:
Not mutagenic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

This hazard class is primarily concerned with substances that may cause mutations in the germ cells of humans that can be transmitted to the progeny. However, the results from mutagenicity or genotoxicity tests in vitro and in mammalian somatic and germ cells in vivo are also considered in classifying substances and mixtures within this hazard class.

For the purpose of classification for germ cell mutagenicity, substances are classified if there is at least positive evidence obtained from experiments in mammals and/or in some cases from in vitro experiments, obtained from:

- somatic cell mutagenicity tests in vivo, in mammals; or

- other in vivo somatic cell genotoxicity tests which are supported by positive results from in vitro mutagenicity assays.

The presented results from in vivo and the in vitro tests are negative, therefore it is concluded that the tested substance is not genotoxic with or without metabolic activation.