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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline 473: GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007

Materials and methods

Test guideline
Qualifier:
according to guideline
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

Constituent 1
Reference substance name:
isodecanol
IUPAC Name:
isodecanol
Constituent 2
Constituent 3
Reference substance name:
Alcohols, C9-11-branched and linear, C10-rich
EC Number:
298-696-6
EC Name:
Alcohols, C9-11-branched and linear, C10-rich
Cas Number:
93821-11-5
IUPAC Name:
C9-11, C10-rich branched alkyl alcohol
Details on test material:
- Name of test material (as cited in study report): Isodecanol Test results for CAS number 93821 -11 -5 are reported as the source substance. This is the previous CAS number for the Alcohols C9 -C11 -iso, C10 rich: isodecanol (Exxal 10) before harmonization of the CAS numbers. CAS number 68526 -85 -2 and 93821 -11 -5 refer to the same substance (i. e. Exxal 10).
- Substance type: colorless liquid
- Physical state: liquid
- Analytical purity: >99% wt total alcohol
- Lot/batch No.: 60917T1602
- Stability under test conditions:
- Storage condition of test material: ambient temperature, protected from light
- Specific gravity: 0.836-0.840 kg/l at 20C

Method

Target gene:
Not applicable
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
- Type and identity of media: Ham’s F-12 with Glutamax-I supplemented with heat-inactivated fetal calf serum (10%), penicillin (100 IU/ml) and streptomycin (100 ug/ml)
- Properly maintained: yes
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 fraction of Aroclor induced male rat liver
Test concentrations with justification for top dose:
Test 1 (5, 10, 20, 30, 40, 80, or 160 ug/ml)

Test 2 (5, 10, 20, 30, 40, 50, 60, 70, 80, 100 ug/ml)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Substrate soluble
- Stock solution – 50 mg/ml
Controls
Negative solvent / vehicle controls:
yes
Remarks:
DMSO alone
Positive controls:
yes
Positive control substance:
other: mitomycin C (without S9) or cyclophosphamide (with S9)
Details on test system and experimental conditions:
METHOD OF APPLICATION:
- Cells were seeded in sterile, screw-capped tissue culture flasks (surface area 25 cm2; 120,000 cells per flask). Test substance was added to the flask with or without S9 fraction.

DURATION
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 14 hours

NUMBER OF REPLICATIONS:
- 2 replicate flasks

NUMBER OF CELLS EVALUATED:
- At least 1000 nuclei

STAIN
- Giemsa

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
Evaluation criteria:
The study was considered valid if the positive controls give a statistically significant increase in the number of aberrant cells and the negative controls are within the historical range.

A response is considered to be positive if a concentration-related increase or a reproducible increase in the number of cells with structural chromosomal aberrations is observed.

A response is considered to be equivocal if the percentage of cells with structural chromosomal aberrations is statistically higher than that of the negative control.

A test substance is considered clastogenic if a concentration-related increase in the percentage of cells with structural chromosomal aberrations over the concurrent control frequencies is observed, or if a single positive test point is observed in both tests at approximately the same dose level.

A test substance is considered to be negative in the chromosomal aberrations test if it produces neither a dose-related increase in the number of structural chromosomal aberrations nor a reproducible positive response at any of the test points.
Statistics:
Data were analyzed by the Fisher’s exact probability test (two-sided) to determine significant differences between treated and control cultures.

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:
Test #1 (80 and 160 ug/ml) Test #2 (80 and 100 ug/ml)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Test #1 - The test substance did not induce a statistically significant increase in the number of aberrant cells at any of the dose levels tested; with or without metabolic activation.

Test #2 - The test substance did not induce a statistically significant increase in the number of aberrant cells at any of the dose levels tested; with or without metabolic activation. The mitotic indices of 50 and 60 ug/ml were clearly reduced to 38% and 52%, respectively of that of the concurrent control.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative

The mammalian chromosomal aberration test to assess the genotoxicity of isodecanol was negative.
Executive summary:

Isodecanol was examined for its potential to induce structural chromosomal aberrations in Chinese Hamster Ovary (CHO) cells, in both the presence and absence of an S9 metabolic activation system.  Two separate chromosomal aberration tests were performed and only differed by the maximum dose tested.  The doses were: Test 1 (5, 10, 20, 30, 40, 80, or 160 ug/ml), Test 2 (5, 10, 20, 30, 40, 50, 60, 70, 80, 100 ug/ml).  Isodecanol did not induce a statistically significant increase in the number of cells with structural chromosomal aberrations at any of the doses chosen with or without metabolic activation; significant cytotoxicity was noted above 80 ug/ml.  Under the conditions in this study, isodecanol was cytotoxic but not a clastogenic agent for CHO cells.  

The mammalian chromosomal aberration test to assess the genotoxicity of isodecanol was negative.