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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study meets the criteria for Klimisch code 1

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
S9 araclor incuded rat liver
Test concentrations with justification for top dose:
10, 20,40,80,120,160 ug/ml
Vehicle / solvent:
tetrahydrofuran for test material
acetone for positive control
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium


DURATION
- Exposure duration: 16 and 40 hours


SPINDLE INHIBITOR (cytogenetic assays): Colcemid
STAIN (for cytogenetic assays): Giemsa stain


NUMBER OF REPLICATIONS: 2


NUMBER OF CELLS EVALUATED: 200 metaphase cells (100 per culture) each containing 19-23 chromosomes


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:

Evaluation criteria:
cells with aberrant chromosomes.
Statistics:
Fisher exact test.

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitate and/or cloudines were present with and without metabolic activation at concentrations of 39 µg/ml and greater.


RANGE-FINDING/SCREENING STUDIES: There was an 81% reduction in cell survival at 160 µg/ml, without metabolic activation, compared with control.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In the initial 16h harvest there were statistically significant increses with dose in the % of aberrant cells for both activated and no activated evaluations. These trends were not reproducible in the repeat 16h harvest and were therefore not considered biologically significant.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The test material was not clatogenic under the conditions of this study.
Executive summary:

In a mammalian cell cytogenetics assay [chromosome aberration], CHO cell cultures were exposed to a petroleum derived calcium salt derivative at concentrations of 0, 10, 20, 40, 80, 120 and 160 µg/ml with and without S9 metabolic activation.

 

Positive controls induced the appropriate response.  There was no evidence of chromosome aberrations induced over background.

 

This study is classified as acceptable.  This study satisfies the requirement for Test Guideline OECD 473 for in vitro cytogenetic mutagenicity data.