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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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study performed following appropriate testing guidelines, GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Versatic 10
- Physical state: clear liquid

Method

Target gene:
chromosome aberration
Species / strain
Species / strain / cell type:
lymphocytes:
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 system - no further details
Test concentrations with justification for top dose:
Test #1
2500, 1250, 625, 500 micrograms/ml

Test #2
1000, 800, 700, 600, 500, 400, 300, 200, 100 micrograms/ml
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Remarks:
DMSO
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
Migrated to IUCLID6: mitomycin C used in the absence of S9 metabolic activation system
Details on test system and experimental conditions:
METHOD OF APPLICATION: in culture


DURATION
- Preincubation period: 3 hours
- Exposure duration: 24 hours

SPINDLE INHIBITOR (cytogenetic assays): colcemid
STAIN (for cytogenetic assays): Giemsa


NUMBER OF REPLICATIONS: two slides from each duplicate culture


NUMBER OF CELLS EVALUATED: At least 1000


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
Evaluation criteria:
For each selected treatment 200 well-spread metaphases containing 46 centromeres were analyzed by microscopic examination for a wide range of structural chromose and chromatid aberrations (gaps, breaks, fragments, dicentrics, rings, interchanges, intrachanges, and other anomalies such as interstital deletions and multiple aberrations.
Statistics:
Fisher's exact probability test

Results and discussion

Test results
Species / strain:
lymphocytes:
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
no statistical increases in the number of cells with chromosomal aberrations
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
only at the highest concentrations tested
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Versatic 10 does not induce chromosome aberrations.
Executive summary:

The test substance Versatic 10 (neodecanoic acid) was examined for its potential to induce structural chromosome aberrations in cultured human lymphocytes in both the absence and presence of a metabolic activation system (S9 mix), in compliance with OECD guideline 473. 

 

Two independent chromosome aberration tests were conducted in both the absence and presence of S9. In the absence of S9, cells were exposed to the test substance continuously for 24 or 48 hours. In the presence of the S9, cells were exposed to the test substance for 3 hours and harvested at 24 or 48 hours later. The choice for the highest concentrations scored was based on toxicity. The test substance was dissolved in DMSO.

 

In neither chromosome aberration assay, Versatic 10 did not induce a statistically significant increase in the percentage of cells with structural chromosome aberrations at any of the concentrations and time points analyzed. The positive controls gave appropriate responses.

 

It is concluded that Versatic 10 is not clastogenic under the conditions used in this study.