Tetrakis(diethyldithiocarbamato-S,S')tellurium

Genetic toxicity: in vitro

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

Test material information

Constituent 1

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:

N2,N2,N6,N6,N6,N6,N9,N9-octaethyl-1λ³,3,5λ³,5λ³,7,7,8λ³,10-octathia-4λ⁸-telluradispiro[3.3⁴.3⁴.3⁴]trideca-1,5,5,8-tetraene-2,6,6,9-tetramine

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 results

Test results 1

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

Test results 2

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