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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
Negative with and without metabolic activation (Ames test); positive without metabolic activation, negative with metabolic activation (Chinese hamster ovary sister chromatid exchange test); positive without metabolic activation, ambiguous with metabolic activation (chromosome aberration test); weakly positive (Basc test); negative (mouse micronucleus test).
Link to relevant study records
Reference
Endpoint:
in vivo mammalian germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
equivalent or similar to
Guideline:
other: Schmid W (1976) The micronucleus test for cytogenetic analysis. In Chemical Mutagens. Edited by Hollaender A. Vol. 4. p 31. Plenum Press, New York.
GLP compliance:
not specified
Type of assay:
micronucleus assay
Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 10 wk to 14 wk
- Weight at study initiation: No data
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
Route of administration:
intraperitoneal
Vehicle:
- Vehicle used: olive oil
- Justification for choice of solvent/vehicle:
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal):
Duration of treatment / exposure:
30 hr
Frequency of treatment:
Treated only once
Remarks:
Doses / Concentrations:
1856 mg/kg bw
Basis:
no data
Remarks:
Doses / Concentrations:
1237 mg/kg bw
Basis:
no data
Remarks:
Doses / Concentrations:
619 mg/kg bw
Basis:
no data
No. of animals per sex per dose:
4
Control animals:
yes
Positive control(s):
No data
Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION:
- Mice were killed and bone marrow smears were prepared 30 hr after treatment.
- The smears were stained according to the method of Schmid (1976).
Statistics:
Statistical significance was determined according to the methods of Kastenbaum & Bowman (1970) Tables for determining the statistical significance of mutation frequencies. Mutation Research 9: 527

Results on mouse bone marrow:

Dose (mg/kg body weight) Surviving:treated mice Mean No. of micronucleated polychromatic erythrocytes (PE)/1000 PE
1856 4:4 1.7
1237 4:4 1.7
619 4:4 1.3
0 (control) 4:4 1.9

No significant difference between the control and treated groups.

Conclusions:
Interpretation of results (migrated information): negative
Wild et al. found that the test material was not genotoxic up to a concentration of 1856 mg/kg body weight in a mouse micronucleus test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

A variety of studies have been performed on the genotoxicity of the substance. Wild et al. (1982) conducted an Ames test, a Basc (Drosophila melanogaster) test, and a mouse micronucleus test on the substance. Galloway et al. (1987) performed a chromosome aberration test and a sister chromatid exchange test.

The mouse micronucleus test by Wild et al. (1982) differs from the current guidelines particularly only a single time point of 30 hours was employed. At the time the study was performed 3 time points were common; 24, 48 and 72 hours. The Ames test lacks testing on E. coli when compared to the current guidelines.

As a consequence of (1) the negative mouse micronucleus test (Wild et al. 1982) (2) the negative Ames test both with and without metabolic activation (Wild et al. 1982), (3) the negative chromosome aberration test with metabolic activation (Galloway et al. 1987), and (4) the negative sister chromatid exchange test (Galloway et al. 1987), the test material can be considered negative for genetic toxicity.

In coming to this conclusion, two results have to be discounted: (1) The Basc test (Wild et al. 1982) was weakly positive but used as a model organism a species of fruit fly, Drosophila melanogaster, that is not especially analogous to humans. This is also not a standard test required by Regulation (EC) No. 1907/2006, but was available in the scientific literature. (2) The chromosome aberration test without metabolic activation was ambiguous (Galloway et al. 1987), but was negative with metabolic activation and metabolic activation can reasonably be expected in vivo.

Genetic toxicity is a concern for toxicology in part because genotoxic substances are often mutagenic, which often leads to carcinogenicity. The availability of a long-term in vivo study that found no neoplastic histopathological effects (Dunnington et al. 1981) supports the finding that the test material is not genotoxic.

As a consequence of the findings of the chromosome aberration test performed by Galloway et al. (1987), an in vitro gene mutation study in mammalian cells was not performed.


Justification for selection of genetic toxicity endpoint
In vivo study.

Justification for classification or non-classification