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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:
experimental study
Adequacy of study:
key study
Study period:
From 5 to 24 June 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP: yes-Guideline not available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Please refer to the executive summary for description of the method.
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): compound 38502
- Storage condition of test material: room temperature
- Other: received on May 26, 1983
The test article was measured and dissolved in DMSO to appropriate concentrations, immediatly before use. Approximately 10 to 20 minutes were taken between the time the test article was sulubilized and the final treatment of cells.

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
- Originally obtained from American Type Culture Collection, Rockville, Maryland
- Properly maintained: yes (cryopreserved)
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S-9 containing 2.4 mg/ml of NADP, 4.5 mg/ml of isocitric acid and 15 µl of Aroclor induced rat liver homogenate/ml.
Test concentrations with justification for top dose:
The test article was tested at six decreasing dose levels from 130.0 nl/ml to 29.99 nl/ml in the activated and non-activated systems.
Vehicle / solvent:
Solvent: DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
triethylenemelamine
cyclophosphamide
Details on test system and experimental conditions:
DURATION
Cells were treated with test substance without S9 for 12 hours, with S9 for 2 hours.

NUMBER OF CELLS EVALUATED: 100

DETERMINATION OF CYTOTOXICITY
- Method: rate of surival cells
Statistics:
Percentage of cells with aberration.

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
The relative cell survival (RCS): 0% at 200 nl/ml, RCS 87% at 60 nl/ml in activated system - 0% at 200 nl/ml and 103 at 60 nl/ml in the nonactivated system.
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: CHO-K1
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Results of chromosome aberration assay-14 hours with activation
 Test article concentration  Number of cells analyzed  Number of aberrations per cell  % of cells with aberration
 130.00 nl/ml  Cells were dead  -  -
 110.07 nl/ml  Cells were dead  -  -
 90.25 nl/ml  100  0  0
 70.40 nl/ml  100  0.02  2
 49.98 nl/ml  100  0.03  2
 29.98 nl/ml  100  0.04  4
 Negative control  100  0.01  1
 Positive control 50 µg/ml  100  1.07  59
 Solvent control  100  0.01  1

Results of chromosome aberration assay-14 hours without activation

 Test article concentration  Number of cells analyzed  Number of aberrations per cells  % of cells with aberration
 80.00 nl/ml  Cells were dead  -  -
 70.00 nl/ml  100  0.02  2
 59.97 nl/ml  100  0.02  2
 49.97 nl/ml  100  0.01  1
 39.98 nl/ml  100  0.04  4
 29.98 nl/ml  100  0.03  2
 Negative control  100  0.04  3
 Positive control 1.0 µg/ml  100  1.34  65
 Solvent control  100  0.06  4

Results of chromosome aberration assay-24 hours with activation

 Test article concentration  Number of cells analyzed  Number of aberrations per cell  % of cells with aberration
 130.00 nl/ml  Cells were dead  -  -
 110.07 nl/ml  Cells were dead  -  -
 90.25 nl/ml  100  0.01  1
 70.40 nl/ml  100  0.05  4
 49.98 nl/ml  100  0.03  3
 29.98 nl/ml  100  0.05  5
 Negative control  100  0.04  4
 Positive control 50 µg/ml  100  2.98  81
 Solvent control  100  0.03  3

Results of chormosome aberration assay-24 hours without activation

 Test article concentration  Number of cells analyzed  Number of aberrations per cell  % of cells with aberration
 80.00 nl/ml  Cells were dead  -  -
 70.00 nl/ml  100  0.02  2
 59.97 nl/ml  100  0  0
 49.97 nl/ml  100  0.01  1
 39.98 nl/ml  100  0.01  1
 29.98 nl/ml  100  0.01  1
 Negative control  100  0.02  2
 Positive control 1.0 µg/ml  100  1.17  47
 Solvent control  100  0.03  3

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Compared to the cells with chromosome aberrations in the solvent control, none of the test doses showed a significant increase in the frequency of cells with chromosome aberrations in the activated and nonactivated system.
In this study no indication of a dose response was observed.
In this study the positive controls caused a significant increase in the number of cells with chromosome aberrations.
Executive summary:

The test item was tested in the chromosome aberration assay using Chinese hamstar ovary cells, with and without metabolic activation. The treated cells were harvested at 14 hours and 24 hours following the initiation of chemical treatment and scored for chromosome aberration. The results indicate that under the test condition, the test article did not cause a significant increase in the frequencies of chromosome abertration in the Chinese hamster ovary cells with and without rat S9 activation.