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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:
1998-01-12 to 1998-05-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it followed OECD guideline 473 recommendations and was GLP compliant. The study is well documented and is scientifically sound.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

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
Details on test material:
- Name of test material (as cited in study report): C20-C24 branched and linear
- Substance type: Alkenes, C20-24
- Physical state: Liquid
- Lot/batch No.: C1829-50A
- Storage condition of test material: Room temperature

Method

Species / strain
Species / strain / cell type:
other: human lymphocytes
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: no
- Periodically checked for karyotype stability: no
- Periodically "cleansed" against high spontaneous background: no
Metabolic activation:
with and without
Metabolic activation system:
S-9
Test concentrations with justification for top dose:
0, 312.5, 625, 1250, 2500, or 5000 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: None reported
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: ethylmethanesulphonate and cyclophosphamide
Details on test system and experimental conditions:
METHOD OF APPLICATION: In medium


DURATION
- Exposure duration: 4 or 20 hours
- Expression time (cells in growth medium): 20 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 18 hours
SPINDLE INHIBITOR (cytogenetic assays): Demecolcine
STAIN (for cytogenetic assays): 5% Gurrs Giemsa R66 for 5 minutes

NUMBER OF REPLICATIONS: Two experiments with two replicates each.


NUMBER OF CELLS EVALUATED:Two hundred cells (one hundred from each replicate)


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

OTHER EXAMINATIONS:
- Determination of polyploidy: yes

Evaluation criteria:
A positive response is recorded when the p value calculated from the statistical analysis of the frequency of cells with aberrations is less than 0.05 when compared to its concurrent control and that there is a dose-related increase in the frequency of cells with aberrations which is reproducible.

Statistics:
Fischer's exact test

Results and discussion

Test results
Species / strain:
other: human lymphocytes
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
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

Under the conditions of this study, C20-C24 alkenes, branched and linear are considered to be non-clastogenic to human lymphocytes in vitro.
Executive summary:

In a mammalian cell cytogenetics assay (chromosome aberration), human lymphocytes (duplicate cultures) were tested for chromosome aberration at dose levels of 0, 312.5, 625, 1250, 2500, or 5000 µg/mL in the presence and absence of metabolic activation. Two independent experiments were conducted with different exposure and harvest times: Experiment 1) 4 hour exposure followed by 16-hours for a total of 20 hour harvest time, ±S9; and Experiment 2) 20 -hour exposure, -S9, or 4-hour exposure,+S9, followed by 16-hours for a total of 20 hour harvest time. Additionally, vehicle (acetone) and positive controls were also utilized in the study design.

 

Treatment with the test material did not result in any statistically significant increase in the frequency of cells with chromosome aberrations. The number of cells with chromosome aberrations in the vehicle control was found to be within the normal range, and the positive controls responded appropriately.

 

Under the conditions of this study, C20-C24 alkenes, branched and linear are considered to be non-clastogenic to human lymphocytesin vitro

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it followed OECD guideline 473 recommendations and was conducted according to GLP.