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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. Read-across to the registered substance is considered scientifically justified.

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)
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): Sasol(TM) 23 Alcohol C10-16 alcohols Type B (also known as Compound 33A)
- Substance type: UVCB substance
- Physical state: liquid
- Lot number: KPT/SAS/DA/2/98

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
Test 1: 0.1 - 500 µg/ml; Test 2: with S9 1 -50 µg/ml, without S9 0.5 - 20 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: none given in report. Standard solvent
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with activation
Details on test system and experimental conditions:
ACTIVATION: 1 ml Aroclor induced rat liver S9 mix, NADP as cofactor
METHOD OF APPLICATION: in medium

DURATION

Exposure duration: Test 1: +S9 3 hours, -S9 18 hours, Test 2: +S9 3 hours; -S9  18 or 32 hours 
- Expression time (cells in growth medium): 18 hours
- Fixation time (start of exposure up to fixation or harvest of cells): Test 1 18 hours; Test 2 18 or 32 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemid (fianl concentration 0.1 mM)

TAIN (for cytogenetic assays): Giesma

NUMBER OF REPLICATIONS: Duplicate cultures, independent repeat assay

NUMBER OF CELLS EVALUATED: 100 per culture

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; other: observation of culture

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes
- Other: intersticial deletions
Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS: The test is considered positive if the  aberration frequency of at least one concentration is significantly above  concurrent control frequencies.
Statistics:
Fisher's exact probability test (two-sided)

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:
+S9 40 µg/ml; -S9 15 µg/ml
Additional information on results:
GENOTOXIC EFFECTS: - With and without metabolic activation:  
There were  no statistically significant increase in total numbers of chromosome aberrations at any dose level tested
There was no increase in the incidence of  polyploids or endoreduplicates.
PRECIPITATION CONCENTRATION: 125 ug/ml. 
MITOTIC INDEX: The mitotic index was measured on 1000 cells  and was  always >40% of control levels and usually >50% for the dose levels which   were scored for chromosome aberrations. 
STATISTICAL RESULTS: Fischers exact probability test (two-sided) did not  indicate any significant difference between test and control groups.
Remarks on result:
other: strain/cell type: Chinese hamster ovary cells (CHO K-1 line)
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Chromosome aberration assay: Test 1

Treatment time 18 hrs

Treatment

Activation

Concentration µg/ml

Number of cells

Total - gaps

Total + gaps

Negative control DMSO

-MA

0

200

0

4

Test substance

 

 

-MA

2.5

200

0

6

-MA

5

200

0

6

-MA

10

200

2

8

Positive control Mitomycin C

-MA

0.025

200

48

48

Treatment time 3 hrs

Treatment

Concentration µg /ml

Number of cells

Total - gaps

Total + gaps

Negative control DMSO

+MA

0

200

0

2

Test substance

 

 

+MA

10

200

1

6

+MA

20

200

1

5

+MA

30

200

1

5

Positive control Cyclophosphamide

+MA

3.75

200

48

48

Chromosome aberration assay: Test 2

Treatment

-MA

Concentration 

µg /ml

Number of cells

Total - gaps

Total + gaps

Treatment time 18 hrs

Negative control DMSO

-MA

0

200

1

5

Test substance

 

 

-MA

5

200

2

8

-MA

7.5

200

0

5

-MA

10

200

1

4

Positive control Mitomycin C

-MA

0.025

200

54

54

Treatment time 3 hrs, incubation 18 hours

Treatment

Concentration

µg /ml

Number of cells

Total - gaps

Total + gaps

Negative control DMSO

+MA

0

200

0

8

Test substance

 

 

+MA

10

200

1

2

+MA

20

200

1

7

+MA

30

200

1

7

Positive control Cyclophosphamide

+MA

3.75

200

105

105

Treatment time 32 hrs

Treatment

Concentration

µg /ml

Number of cells

Total - gaps

Total + gaps

Negative control DMSO

-MA

0

200

0

8

Test substance

-MA

10

200

0

7

Treatment time 3 hrs, incubation 32 hours

Treatment

Concentration 

µg /ml

Number of cells

Total - gaps

Total + gaps

Negative control DMSO

+MA

0

200

2

3

Test substance

+MA

30

200

0

5

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without activation

C12 AND 13 ALCOHOLS; LINEAR AND MONOBRANCHED, TYPE 2 (also known as Compound 33A) has been tested in a valid study according to OECD TG 473 and under GLP in CHO K1 cells. The test substance did not increase the incidence of chromosome aberrations in Chinese hamster ovary cells at dose levels up to cytotoxic concentrations in the presence or absence of metabolic activation. The result of the repeat experiment confirmed that of the intial assay. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this test.