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EC number: 205-710-6 | CAS number: 148-18-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Sodium diethyldithiocarbamate (SDEC) was negative in Ames test with Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100, chromosome aberration assay with CHO cells and sister chromatid exchange assay with CHO cells. The results of an in vitro mouse lymphoma assay were positive, although irregular dose-responses were obtained. No in vivo genotoxicity studies were available for assessment. However, based on the negative results of carcinogenicity study with rats and mice, the substance is considered to be non-genotoxic. It shall be mentioned that the form of the test material was not specified, but tests were performed up to cytotoxic concentrations.
Link to relevant study records
- 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
- 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
- Target gene:
- his
- 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
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- for TA 1535 and TA 100
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylenediamine
- Remarks:
- for TA98
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- for TA97 and TA 1537
- 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.
- 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 - 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.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- 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
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- The experimental procedure used was based upon those described by McGregor et al. (Environ. Mol. Mutagen. 1988, 15, 85-154; Environ. Mol. Mutagen. 1988,11, 91-118; Environ. Mol. Mutagen. 1987, 9, 143-160).
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian cell gene mutation tests using the thymidine kinase gene
- Target gene:
- thymidine kinase locus (tk)
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- without
- Metabolic activation system:
- rat S9
- Test concentrations with justification for top dose:
- Without S9: 1st experiment 0, 0.3125, 0.625, 1.25, 2.5, 5 and 10 μg/mL; 2nd experiment 0, 0.5, 1, 2, 3 and 4 μg/mL; 3rd experiment 0, 0.063, 0.125, 0.25, 0.5 and 1 μg/mL; 0, 0.031, 0.063, 0.0125, 0.25, 0.5 and 1 μg/mL
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: -S9: ethyl methanesulfonate (250 μg/mL), methyl methanesulphonate (15-20 μg/mL); + S9: 3-methylcholanthrene (2.5 μg/mL).
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 4 hr
- Expression time (cells in growth medium): 2 days
NUMBER OF REPLICATIONS: vehicle control, four cultures; positive control, two cultures; at least five test compound concentrations, two cultures per concentration.
NUMBER OF CELLS EVALUATED: 3 x 10e6
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency. The highest concentration used in preliminary toxicity test was 5 mg/ml, unless indicated otherwise by poor substance solubility.Four trial
OTHER
- Test compound concentrations were primarily two-fold dilutions from the highest testable concentration, as estimated from the toxicity test. - Evaluation criteria:
- A response was considered positive when the dose-related trend and the response at one of the tree highest acceptable doses were statistically significant. A test was considered positive when, out of three trials, a positive trial was reproducible.
- Statistics:
- Dose trend test (Barlow et al., 1972) and a variance analysis of pair-wise comparisons of each dose against the vehicle control.
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Four trials were performed in the absence of S9 mix, all of which were judged to be positive and manifested irregular dose-related responses. In the 1st and 2nd trials survival was greated and the induced mutant fraction lowest at 1-2 μg/mL; survival was lower and mutant fractions were higher at both lower and higher concentrations. In the two subsequent trials, 1 μg/mL was the highest dose tested, but lower doses were both more toxic and more mutagenic, at least from 0.063 μg/mL upwards. The mutagenic responses were essentially reproducible and mirrored the survival trend.
- Conclusions:
- The test material SDEC showed a positive response in this in vitro mouse lymphoma assay performed with mouse lymphoma L5178Y cells.
- Executive summary:
In an vitro mouse lymphoma assay performed according to the procedure similar to OECD guideline 476, the ability of SDEC to cause genotoxicity was tested in mouse lymphoma L5178Y cells. The form of the test substance was not specified. In total 4 experiments were performed without metabolic activation, using the following test concentrations: 1st experiment 0, 0.3125, 0.625, 1.25, 2.5, 5 and 10 μg/mL; 2nd experiment 0, 0.5, 1, 2, 3 and 4 μg/mL; 3rd experiment 0, 0.063, 0.125, 0.25, 0.5 and 1 μg/mL; 4th experiment 0, 0.031, 0.063, 0.0125, 0.25, 0.5 and 1 μg/mL. All of the trials were judged to be positive and manifested irregular dose-related responses. In the 1st and 2nd trials survival was greater and the induced mutant fraction lowest at 1-2 μg/mL; survival was lower and mutant fractions were higher at both lower and higher concentrations. In the two subsequent trials, 1 μg/mL was the highest dose tested, but lower doses were both more toxic and more mutagenic, at least from 0.063 μg/mL upwards. The mutagenic responses were essentially reproducible and mirrored the survival trend.
- 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:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Principles of method if other than guideline:
- Tested using a standard protocol: Galloway SM, Bloom AD, Resnick MA, Margolin BH, Nakamura F, Archer P, Zeiger E (1985): Development of a standard protocol for in vitro cytogenetic testing with Chinese hamster ovary cells: Comparison of results for 22 compounds in two laboratories. Environ Mutagen 7:1-51.
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- - Source : Dr. Sheila Galloway (Litton Bionetics, Kensington, MD)
- Type and identity of media: McCoy's 5A (modified) medium (KC Biological, Lenexa, KS)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Growth and treatment conditions: Galloway SM, Bloom AD, Resnick MA, Margolin BH, Nakamura F, Archer P, Zeiger E (1985): Development of a standard protocol for in vitro cytogenetic testing with Chinese hamster ovary cells: Comparison of results for 22 compounds in two laboratories. Environ Mutagen 7:1-51. - Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced S9 rat liver microsomal fraction (Microbiological Associates, Kensington, MD)
- Test concentrations with justification for top dose:
- Without metabolic activation, 1st experiment: 0.0; 0.1; 0.3 and 1.0 µg/mL;
With metabolic activation: 0.0; 15.2; 50.7 and 152 µg/mL - Vehicle / solvent:
- - Solvent used: water
- Stock solutions were prepared at 500 mg/mL, or at the limit of solubility, and diluted 1:100 in medium to obtain a high test concentration of 5 mg/mL - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
Without metabolic activation:
DURATION
- Exposure duration: 8 hours
- Fixation time (start of exposure up to fixation or harvest of cells): After 8 hours of exposure, cells are washed to remove the test chemical, and treated with colcemid (10E-6 M) for 2-2.5 hr before cell harvest.
With metabolic activation:
DURATION
- Exposure duration: 2 hours
- Incubation period: incubated at 37°C with medium for 8 hr.
- Fixation time (start of exposure up to fixation or harvest of cells): After incubation, colcemid was added and the cells were harvested 2 hr later.
STAIN (for cytogenetic assays): slides were stained in 5% Giemsa for 5 min
NUMBER OF REPLICATIONS: one
NUMBER OF CELLS EVALUATED: One hundred cells were scored for each of three concentrations
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index
OTHER EXAMINATIONS:
Cells were analyzed for the following categories of chromosomal aberrations: "Simple,"defined as chromatid gap, break, fragment, and deletion, chromosome gap and break, double minutes; "complex" rearrangements such as interstitial deletion, triradial, quadriradial, ring, dicentric chromosome; and "other," defined as pulverized chromosome, polyploid cell, or endoreduplicated cell. Chromatid and chromosome gaps were recorded but were not used for evaluation. The frequency of polyploid or endoreduplicated cells was only noted when it seemed excessive; however, these categories were never included in the totals for statistical analysis. - Statistics:
- The statistical procedures for evaluation of test data are described in Galloway SM. Armstrong MA, Reuben C, Colman S, Brown C, Cannon AD. Bloom AD, Nakamura F, Ahmed M, Duk S, Rimpo J, Margolin BH, Resnick MA, Anderson B, Zeiger E (1987): Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: Evaluations of 108 chemicals. Environ Mol Mutagen l0(Suppl 10):1-175.
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- The test substance SDEC did not induce chromosomal damage in this in vitro genotoxicity test with CHO cells, in the presence and absence of metabolic activation.
- Executive summary:
In the present study, the ability of sodium diethyldithiocarbamate (SDEC) to induce chromosome aberrations and sister chromatid exchange in Chinese hamster ovary (CHO) cells was tested. In the first study, the following test concentrations have been used: without metabolic activation, 0.0; 0.1; 0.3 and 1.0 µg/mL; with metabolic activation (rat liver S9 fraction), 0.0; 15.2; 50.7 and 152.0 µg/mL. It is not clear which form of the substance was tested, although the purity is stated to exceed 99%. The substance was tested up to cytotoxic concentrations. Under the conditions of this test, SDEC does not induce chromosomal aberrations.
Referenceopen allclose all
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
Results of 4 trials with sodium diethyldithiocarbamate without S9 mix.
Concentration μg/ml | CE | RTG | MC | MF | AVE MF |
0 (vehicle control) | 74 87 75 100 | 106 95 83 117 | 97 130 127 108 | 43 50 56 36 |
46 |
0.3125 | 67 74 | 53 57 | 240 238 | 119 107 |
113 |
0.625 | 77 61 | 71 61 | 257 196 | 111 107 |
109 |
1.25 | 76 75 | 67 82 | 175 134 | 76 60 |
68 |
2.5 | 74 59 | 54 48 | 84 141 | 38 79 |
58 |
5 | 37 37 | 4 4 | 282 347 | 252 315 |
284 |
10 | Lethal Lethal |
|
|
|
|
EMC 250 μg/mL | 60 64 | 67 64 | 558 464 | 311 243 |
277 |
MMS 20 μg/mL | 31 37 | 19 27 | 342 352 | 370 314 |
342 |
Concentration μg/ml | CE | RTG | MC | MF | AVE MF |
0 (vehicle control) | 83 84 85 88 | 82 99 115 105 | 117 90 86 92 | 47 36 34 35 |
38 |
0. 5 | 66 67 | 25 29 | 339 281 | 172 140 |
156 |
1 | 51 58 | 39 60 | 153 201 | 99 98 |
99 |
2 | 58 49 | 36 32 | 291 208 | 168 143 |
155 |
3 | 53 45 | 10 8 | 521 539 | 328 401 |
364 |
4 | Lethal Lethal |
|
|
|
|
MMS 15 μg/mL | 7r 13 | 3 5 | 88 101 | 409 266 |
|
r = Rejected when 50% > CE > 120% or RTG < 1%
Concentration μg/ml | CE | RTG | MC | MF | AVE MF |
0 (vehicle control) | 80 53 70 82 | 113 88 106 92 | 91 83 107 129 | 38 53 51 52 |
48 |
0.063 | 34 40 | 14 19 | 104 196 | 103 163 |
133 |
0.125 | 44 37 | 22 21 | 230 172 | 173 154 |
163 |
0.25 | 46 40 | 35 29 | 210 203 | 152 169 |
161 |
0.5 | 50 53 | 41 40 | 214 300 | 142 188 |
165 |
1 | 64 49 | 51 78 | 184 109 | 96 74 |
85 |
MMS 20 μg/mL | 24 20 | 18 14 | 413 242 | 582 414 |
498 |
Concentration μg/ml | CE | RTG | MC | MF | AVE MF |
0 (vehicle control) | 62 67 69 58 | 94 93 107 106 | 71 64 84 91 | 38 32 40 52 |
41 |
0.011 | 46 54 | 25 51 | 124 163 | 90 100 |
95 |
0.063 | 40 48 | 11 13 | 194 326 | 163 228 |
195 |
0.125 | 39 47 | 11 12 | 213 265 | 182 188 |
183 |
0.25 | 73 56 | 18 14 | 299 213 | 137 126 |
126 |
0.5 | 65 54 | 28 22 | 239 211 | 122 131 |
126 |
1 | 62 58 | 31 26 | 184 178 | 99 103 |
101 |
MMS 15 μg/mL | 21 16 | 18 13 | 128 149 | 206 271 |
239 |
CE = cloning efficiency; RTG = relative total growth (calculated as total suspension growth x CE); MF = mutant fraction (calculated as 200 x mutant colonies per plate / total clones per plate); MC = mutant colony count; AVE MF = group average mutant fraction; underline = P < 5%
Table 1. Results of chromosome aberration test with sodium diethyldithiocarbamate in the absence of metabolic activation.
Dose (μg/mL) | Cells | Percentage cells with aberrations | ||
Total | Simple | Complex | ||
0.0 | 100 | 3.00 | 3.00 | 0.00 |
0.1 | 100 | 1.00 | 1.00 | 0.00 |
0.3 | 100 | 4.00 | 4.00 | 0.00 |
1.0 | 100 | 0.00 | 0.00 | 0.00 |
Positive control (MMC) 5.000 | 50 | 72.00 | 46.00 | 48.00 |
Table 2. Results of chromosome aberration test with sodium diethyldithiocarbamate with metabolic activation.
Dose (μg/mL) | Cells | Percentage cells with aberrations | ||
Total | Simple | Complex | ||
0.0 | 100 | 2.00 | 2.00 | 0.00 |
15.2 | 100 | 6.00 | 5.00 | 1.00 |
50.7 | 100 | 4.00 | 3.00 | 1.00 |
152 | 100 | 4.00 | 4.00 | 0.00 |
Positive control (CP) 50.0000 | 50 | 42.00 | 24.00 | 30.00 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Several in vitro tests with sodium diethyldithiocarbamate (SDEC) were available for assessment. Its ability to induce gene mutation in bacteria was studied by Mortelmans et al., 1985, in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at dose levels of 0.0, 33.0, 100.0, 333.0, 1000.0, 3333.0 and 10000.0 µg/plate, with and without metabolic activation. The study unfortunately does not specify which form of the substance (anhydrous, trihydrate or aqueous solution) was tested, although the purity is stated to be 99%; nevertheless, as the substance is manufactured and marketed solely as 26% aqueous solution, it is considered to be acceptable to use the results of this study for risk characterization. No increased number of revertants was found, indicating that the substance is not mutagenic in Ames test.
Loveday et al., 1989, studied the ability of sodium diethyldithiocarbamate (SDEC) to induce chromosome aberrations and sister chromatid exchange in Chinese hamster ovary (CHO) cells. In the first study, the following test concentrations have been used: without metabolic activation, 0.0; 0.1; 0.3 and 1.0 µg/mL; with metabolic activation, 0.0; 15.2; 50.7 and 152.0 µg/mL. Also in this case, it is not clear which form of the substance was tested, although the purity is stated to exceed 99%. The substance was tested to its toxic level and the results were negative.
In the sister chromatid exchange assay, two experiments without and one with metabolic activation were performed, using the following concentrations: without metabolic activation, 1st experiment: 0.0; 0.05; 0.075 and 0.1 µg/mL; second experiment 0.0, 0.075, 0.1 and 0.15 µg/mL; with metabolic activation: 0.0; 0.318; 0.9540 and 3.1800 µg/mL. The initial experiment without S9 yielded a positive response at the highest dose tested, when an extended harvest time (30 hr instead of 26 hr) was used. However, this response was not reproducible, and the chemical was judged negative.
Also an in vitro mouse lymphoma assay (McGregor et al., 1991) was available for assessment, performed according to the procedure similar to OECD guideline 476. Also in this case the form of the substance was not specified. In total 4 experiments were performed without metabolic activation, using the following test concentrations: 1st experiment 0, 0.3125, 0.625, 1.25, 2.5, 5 and 10 μg/mL; 2nd experiment 0, 0.5, 1, 2, 3 and 4 μg/mL; 3rd experiment 0, 0.063, 0.125, 0.25, 0.5 and 1 μg/mL; 4th experiment 0, 0.031, 0.063, 0.0125, 0.25, 0.5 and 1 μg/mL. All of the trials were judged to be positive and manifested irregular dose-related responses. In the 1st and 2nd trials survival was greater and the induced mutant fraction lowest at 1-2 μg/mL; survival was lower and mutant fractions were higher at both lower and higher concentrations. In the two subsequent trials, 1 μg/mL was the highest dose tested, but lower doses were both more toxic and more mutagenic, at least from 0.063 μg/ml upwards. The mutagenic responses were essentially reproducible and mirrored the survival trend.
Usually, when positive results are observed in the in vitro studies, the performance of in vivo studies needs to be considered by the registrant in accordance with Column 2 of REACH Annex VIII. No in vivo genotoxicity studies with sodium diethyldithiocarbamate (SDEC) were available. However, a reliable negative carcinogenicity study with two species, rats and mice, was available (see Section 7.7 for further details), suggesting that the substance does not induce genetic damage in vivo. Therefore, based on the overall evidence, sodium diethyldithiocarbamate (SDEC) is concluded to be non-genotoxic.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
Based on the results of the negative carcinogenicity study with rats and mice, classification of sodium diethyldithiocarbamate (SDEC) in its manufactured and marketed form (as 26% aqueous solution) for genotoxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. These results are also considered to be applicable to the anhydrous substance.
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