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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
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Principles of method if other than guideline:
The test was performed according to the NTP protocol for Chinese Hamster Ovary Cell Cytogenetics (CA test). This protocol has been published (Galloway et al., 1985; PMID 3967632)
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrakis(diethyldithiocarbamato-S,S')tellurium
EC Number:
244-121-9
EC Name:
Tetrakis(diethyldithiocarbamato-S,S')tellurium
Cas Number:
20941-65-5
Molecular formula:
C20H40N4S8Te
IUPAC Name:
tetrakis(diethyldithiocarbamato-S,S')tellurium
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Name as cited in report: Ethyl Tellurac
- Source of test material: Radian Corporation

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Remarks:
CHO-W-B1
Details on mammalian cell type (if applicable):
CELLS USED
- Methods for maintenance in cell culture: 5% CO2, maximum 37°C

MEDIA USED
- Type and identity of media: McCoy's 5A medium supplemented with fetal calf serum (10%), L-glutamine (2mM), and antibiotics (100 units/mL penicillin and 100 µg/mL streptomycin)
Cytokinesis block (if used):
Colcemid
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced male Sprague-Dawley rat liver S9
Test concentrations with justification for top dose:
JUSTIFICATION
The dose levels were determined from the information on cell cycling and toxicity obtained in a CA test.

DOSES
- without S9: 0.032, 0.1, 0.15, 0.32 µg/mL
- with S9: 0.1, 0.32, 1.0, 15.0 µg/mL
Vehicle / solvent:
- Vehicle used: DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
mitomycin C
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 8-15 hours (without S9) or 2 hours (with S9). Incubation time without S9 was determined from the information on cell cycling form the SCE test: if cell cycle delay was anticipated in the CA test, the incubation period was extended to permit accumulation of sufficient cells in first metaphase for analysis
- Expression time (cells in growth medium): 10 hours (only following incubation with S9)
- Fixation time (start of exposure up to fixation or harvest of cells): 14 hours

SPINDLE INHIBITOR:
Colcemid, added during the final 2-3 hours of incubation

STAIN:
Giemsa

NUMBER OF REPLICATIONS:
1

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:
Two to three hours after addition of colcemid, cells were collected by mitotic shake-off and treated for up to 3 min at room temperature with hypotonic KCl (75 mM). Cells were then washed twice with fixative (3:1, methanol:glacial acetic acid, v/v), dropped onto slides, and air-dried

NUMBER OF CELLS EVALUATED:
100
Statistics:
Statistical analyses were performed to compare exposed cells to vehicle controls.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Remarks:
CHO-W-B1
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
Chinese hamster Ovary (CHO)
Remarks:
CHO-W-B1
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

Table 1. Overview results without S9 mix

 

Dose

µg/mL

Total Aberrations

Complex Aberrations

Simple Aberrations

Other Aberrations

No. of Abs

Abs Per Cell

% Cells with abs

No. of Abs

Abs Per Cell

% Cells with abs

No. of Abs

Abs Per Cell

% Cells with abs

No. of Abs

Abs Per Cell

% Cells with abs

Dimethyl Sulfoxide

0         

3

0.03

3

0

0

0

3

0.03

3

0

0

0

Test chemical

 0.032     

10

0.1

8

2

0.02

2

8

0.08

6

0

0

0

Test chemical

 0.1       

26

0.26

19

0

0

0

26

0.26

19

0

0

0

Test chemical

 0.32      

15

0.15

11

2

0.02

2

13

0.13

9

0

0

0

Positive control: Mitomycin-C

 0.15      

42

0.42

29

14

0.14

11

28

0.28

22

0

0

0

Trend:

2.57

0.904

2.379

 

Probability:

0.005

0.183

0.009

 

Table 2. Overview results with S9 mix

 

Dose

µg/mL

Total Aberrations

Complex Aberrations

Simple Aberrations

Other Aberrations

No. of Abs

Abs Per Cell

% Cells with abs

No. of Abs

Abs Per Cell

% Cells with abs

No. of Abs

Abs Per Cell

% Cells with abs

No. of Abs

Abs Per Cell

% Cells with abs

Dimethyl Sulfoxide

0

4

0.04

4

1

0.01

1

3

0.03

3

0

0

0

Test chemical

0.1

4

0.04

3

1

0.01

1

3

0.03

2

0

0

0

Test chemical

0.32

6

0.06

6

2

0.02

2

4

0.04

4

0

0

0

Test chemical

1

6

0.06

6

2

0.02

2

4

0.04

4

0

0

0

Positive control: Mitomycin-C

0.15

19

0.38

30

7

0.14

14

12

0.24

20

0

0

0

Trend:

0.948

0.737

0.632

 

Probability:

0.172

0.231

0.264

 

Applicant's summary and conclusion