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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)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
lymphocytes:
Details on mammalian cell type (if applicable):
Cultures of human lymphocytes are primary cell cultures recommended by international regulations for the mammalian chromosome aberration test; they have a stable karyotype with 46 chromosomes and an average cell cycle time of 13-14 hours.Cultures of human lymphocytes were prepared from whole blood pooled from healthy males donors.
Additional strain / cell type characteristics:
not applicable
Test concentrations with justification for top dose:
Mitotic index analysis:Test 1 (3-hour treatment without activation): 0, 500, 1000, 1500, 2000, 2500, 2750, 3000, 3250, 3500, 3750 and 4000 µg/mL Test 1 (3-hour treatment with activation): 0, 625, 1250, 2500, 3500, 4000, 4500 and 5000 µg/mL Test 2 (20-hr without activation ): 0, 500, 1000, 1250, 1500, 1750, 2000, 2500, 3000, 3500, 4000, 4500 and 5000 µg/mL Test 2 (3-hour treatment with activation):0, 625, 1250, 2500, 3500, 4000, 4500 and 5000 µg/mL Metaphase analysisTest 1 (3-hour treatment without activation): 0, 1000, 2000, 3250 and 3500 µg/mL, Test 1 (3-hour treatment with activation): 0, 1250, 2500 and 5000 µg/mL, Test 2 (20-hour without activation ): 0, 1500, 2000 and 2500 µg/mL, Test 2 (3-hour treatment with activation):0, 1250, 2500 and 4500 µg/mL,

Results and discussion

Test results
Key result
Species / strain:
lymphocytes:
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/ cell type tested Migrated from field 'test system'

Any other information on results incl. tables

Table 7.6.1.1 Metaphase analysis in Test 1

Substance concentration

(µg/mL)

Cells with aberrations excluding gaps

Cells with aberrations including gaps

Relative cell count

Individual values per 100 cells observed (%)

Mean (%)

Individual values per 100 cells observed (%)

Mean (%)

Method without S9 mix / 3 h. time exposure

0

(culture medium)

0

0

0.0

0

0

0.0

100

1000

0

0

0.0

1

0

0.5

115

2000

0

1

0.5

0

1

0.5

109

3250

1

1

1.0

1

3

2.0

91

3500

2

 

2.0

2

 

2.0

25

0.1

(Mitomycin C)

10

12

11.0***

11

13

12.0***

-

Method with S9 mix / 3 h. time exposure

0

(Culture medium)

0

0

0.0

1

0

0.5

100

1250

0

1

0.5

1

2

1.5

110

2500

1

2

1.5

4

3

3.5

100

5000

0

0

0.0

1

3

2.0

70

6

(Cyclophosphamide))

15

16

15.5***

23

20

21.5***

-

***P<0.001; **P<0.01; otherwise P>0.01

Table7.6.1.2 Metaphase analysis in Test 2

Substance concentration

(µg/mL)

Cells with aberrations excluding gaps

Cells with aberrations including gaps

Relative cell count

Individual values per 100 cells observed (%)

Mean (%)

Individual values per 100 cells observed (%)

Mean (%)

Method without S9 mix / 3 h. time exposure

0

(Culture medium)

2

2

2.0

5

5

5.0

100

1500

2

2

2.0

3

2

2.5

79

2000

2

1

1.5

4

2

3.0

56

2500

1

2

1.5

2

4

3.0

45

0.1

(Mitomycin C)

19

21

20.0***

28

24

26.0***

-

Method with S9 mix / 20 h. time exposure

0

(Culture medium)

1

0

0.5

1

1

1.0

100

1250

2

0

1.0

3

1

2.0

100

2500

2

0

1.0

4

1

2.5

95

4500

2

1

1.5

2

2

2.0

58

6

(Cyclophosphamide))

13

11

12.0***

19

14

16.5***

-

***P<0.001; **P<0.01; otherwise P>0.01

Applicant's summary and conclusion