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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
Key study: Test method equivalent or similar to OECD Guideline 471. The test item was found to be positive in the base-change-type strains (E.coli WP2 hcr and Salmonella typhimurium TA1535 and TA100). Sodium dimethyldithiocarbamate is considered to be genotoxic in vitro. Supporting study: No details on test method. Only results were reported. Sodium dimethyldithiocarbamate was found to be mutagen for TA 100.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test method equivalent or similar to OECD Guideline 471.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA1538, TA 98, TA 100 and E. coli WP2 hcr.
Metabolic activation:
with and without
Metabolic activation system:
S9 mix.
Test concentrations with justification for top dose:
Up to 5000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO.
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
Positive controls:
yes
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation).
To 2 ml of the top agar were added 0.1 ml of one of bacterial suspensions in phosphate buffer (1/15 M), 0.1 ml of the solution of the test item and, when required, 0.5 ml of the S9 mix (0.3 ml of S9 fraction/ml S9 mix). The contents were poured onto the surface of a minimal agar plate with modified Vogel-Bonner E medium. Plates were incubated at 37 ºC for 2 days, after which the number of revertant colonies on each plate was counted.
Species / strain:
S. typhimurium, other: S. typhimurium TA 1537, TA 1538 and TA98.
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
other: S. typhimurium TA 1535 and E.coli WP2 hcr.
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
(weakly positive)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
The test item was positive in the base-change-type strains (E.coli WP2 hcr and Salmonella typhimurium TA1535 and TA100), but negative in the frameshift-type strains (TA 1537, TA 1538 and TA 98). The response in S. typhimurium TA 1535 and E.coli WP2 hcr was defined to be weakly positive as the number of revertants did not reach the criteria for a positive result but showed a dose-resposne relationship.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
positive

The test item was found to be positive in the base-change-type strains (E.coli WP2 hcr and Salmonella typhimurium TA1535 and TA100). Sodium dimethyldithiocarbamate is considered to be genotoxic in vitro.
Executive summary:

Sodium dimethyldithiocarbamate was tested for mutagenicity in a bacterial reversion-assay system with 5 strains (TA 100, TA 98, TA 1535, TA 1537 and TA 1538) of Salmonella typhimurium and a strain (WP2 hcr) of Escherichia coli, following a method equivalent or similar to the OECD Guideline 471. The experiment was carried out in the presence and the absence of metabolic activation (S9 mix). The test item was dissolved in DMSO and was tested at concentrations up to 5000 µg/plate. The test item was found to be positive in the base-change-type strains (E.coli WP2 hcr and Salmonella typhimurium TA1535 and TA100), but negative in the frameshift-type strains (TA 1537, TA 1538 and TA 98). From the results of the present study, the test substance is considered to be genotoxic in vitro.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vitro:

Key study: Sodium dimethyldithiocarbamate was tested for mutagenicity in a bacterial reversion-assay system with 5 strains (TA 100, TA 98, TA 1535, TA 1537 and TA 1538) of Salmonella typhimurium and a strain (WP2 hcr) of Escherichia coli, following a method equivalent or similar to the OECD Guideline 471. The experiment was carried out in the presence and the absence of metabolic activation (S9 mix). The test item was dissolved in DMSO and was tested at concentrations up to 5000 µg/plate. The test item was found to be positive in the base-change-type strains (E.coli WP2 hcr and Salmonella typhimurium TA1535 and TA100), but negative in the frameshift-type strains (TA 1537, TA 1538 and TA 98). From the results of the present study, the test substance is considered to be genotoxic in vitro.

Supporting study: The mutagenicity of sodium dimethyldithiocarbamate was tested using E. coli WP2 hcr, S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, and TA 100. The test substance was found to be mutagen for TA 100. However, it was not mutagenic for the frameshift strains (TA 1537, TA 1538, and TA 98).

The results of these studies showed positive evidence of the mutagenicity potential of sodium dimethyldithiocarbamate. Although these in vitro studies are not sufficient for classification, may offer supporting information in the event of in vivo mutagenicity data.


Justification for selection of genetic toxicity endpoint
Only one reliable study available.

Justification for classification or non-classification

Only in vitro mutagenicity studies are available for sodium dimethyldithiocarbamate. There are no studies of exposed humans and no genotoxicity tests performed in vivo. Thus, there are no data available that would justify classification for germ cell mutagenicity according to CLP criteria.