Sodium diethyldithiocarbamate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Materials and methods

Principles of method if other than guideline:

Method; Other: Salmonella preincubation assay (modification of the standard plate incorporation assay)
Method; Other: Ames BN, McCann J, Yamasaki E (1975): Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutat Res 31:347-364.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium diethyldithiocarbamate

EC Number:

205-710-6

EC Name:

Sodium diethyldithiocarbamate

Cas Number:

148-18-5

Molecular formula:

C5H11NS2.Na

IUPAC Name:

sodium (diethylcarbamothioyl)sulfanide

Method

Target gene:

his

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

rat liver S-9, Aroclor 1254-induced or hamster liver S-9, Aroclor 1254-induced

Test concentrations with justification for top dose:

0.0, 33.0, 100.0, 333.0, 1000.0, 3333.0 and 10000.0 µg/plate

Vehicle / solvent:

- Solvent used: DMSO

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

for TA 1535 and TA 100

Controls 2

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine

Remarks:

for TA98

Controls 3

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

for TA97 and TA 1537

Controls 4

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

for all strains with hamster and rat liver metabolic activation systems

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes at 37°C followed by 48 hours at 37°C

NUMBER OF REPLICATIONS: 3

Evaluation criteria:

The criteria used for data evaluation were as follows: 1) mutagenic response: a dose-related, reproducible increase in the number of revertants over background, even if the increase was less than twofold; 2) nonmutagenic response: when no increase in the number of revertants was elicited by the chemical; 3) questionable response: when there was an absence of a clear-cut dose-related increase in revertants; when the dose-related increases in the number of revertants were not reproducible; or when the response was of insufficient magnitude to support a determination of mutagenicity.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
initially tested with strain TA100 in the presence and the absence of the metabolic activation systems, over a wide dose range

Any other information on results incl. tables

Dose	TA 100						TA 1535
	NA		10% HLI		10%RLI		NA		10% HLI		10%RLI
µg/plate	MEAN	SEM	MEAN	SEM	MEAN	SEM	MEAN	SEM	MEAN	SEM	MEAN	SEM
0.0 (DMSO)	96	1.5	104	3.0	97	4.2	8	1.2	8	1.3	13	0.3
33.0	75	2.6	94	4.7	82	5.9
100.0	80	1.5	83	1.9	85	3.2	11	1.2	15	1.9	12	3.8
333.0	83	5.6	85	12.5	81	1.2	8	1.5	9	1.8	15	1.7
1000.0	65	12.1	102	5.8	97	7.0	7	1.7	10	2.7	10	1.5
3333.0	0	0.0	2	1.5	1	1.0	5	1.5	7	0.9	7	2.4
10000.0							0	0.0	1	0.9	0	0.5
POS	384	20.4	2285	33.2	2285	35.2	117	8.4	131	29.6	37	6.6

 

Dose	TA 1537						TA 98
	NA		10% HLI		10%RLI		NA		10% HLI		10%RLI
µg/plate	MEAN	SEM	MEAN	SEM	MEAN	SEM	MEAN	SEM	MEAN	SEM	MEAN	SEM
0.0 (DMSO)	10	1.3	3	0.3	7	1.2	11	1.2	12	2.6	16	3.1
33.0
100.0	1	0.3	3	0.6	6	0.3	12	1.9	12	2.0	15	2.6
333.0	1	0.6	3	0.3	3	2.8	7	1.9	17	2.3	18	1.5
1000.0	1	0.6	2	0.9	2	0.7	8	1.2	15	5.2	14	4.2
3333.0	0	0.3	1	0.9	2	0.3	7	1.8	11	2.5	10	1.8
10000.0	0	0.0	1	0.3	1	0.3	0	0.0	10	1.5	8	1.5
POS	28	3.8	89	8.5	130	15.5	92	10.2	883	25.4	127	13.3

Abbreviations:

POS: positive control; NA, not activated; RLI, rat liver S-9, Aroclor 1254-induced; HLI, hamster liver S-9, Aroclor 1254-induced

Applicant's summary and conclusion

Conclusions:

No increased number of revertants was found, indicating that the substance SDEC is not mutagenic in Ames test.

Executive summary:

In a Salmonella preincubation assay, according to Ames et al. (1975), strains TA1535, TA 1537, TA 98 and TA 100 of S. typhimurium were exposed to SDEC at of 0.0, 33.0, 100.0, 333.0, 1000.0, 3333.0 and 10000.0 µg/plate, with and without metabolic activation. The test substance was tested up to the required limit concentrations (up to 5000 µg/plate). The compound did not induce any significant increase in the observed numbers of revertant colonies in any of the tester strains used, neither in the presence or absence of metabolism (S9). The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background. In conclusion, the test substance SDEC is not-mutagenic in the Ames test.