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EC number: 205-238-0 | CAS number: 136-30-1
- 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
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- 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 dibutyldithiocarbamate (SDBC) in its manufactured form (as 47.5% aqueous solution) was not mutagenic in Ames test with and without metabolic activation up to dose levels of 5000 µg per plate (2375 µg per plate for pure substance). No data on its ability to induce gene mutations and chromosome aberrations in mammalian cells were available; however, based on the read-across with its structural analogues sodium dimethyldithiocarbamate (SDMC), and sodium diethyldithiocarbamate (SDEC) which are not genotoxic (based on in vivo studies), SDBC is concluded to have no genotoxic potential.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- DNA base pairs
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- derived from rat liver (S-9 mix)
- Test concentrations with justification for top dose:
- 50, 158, 500, 1580 and 5000 µg per plate (for 47.5% aqueous solution of the substance), corresponding to 23.75, 75.05, 237.5, 750.5 and 2375 µg per plate for pure (anhydrous) substance
- Vehicle / solvent:
- - Solvent used: distilled water
- Negative solvent / vehicle controls:
- yes
- Remarks:
- with and without S-9
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Incubation period: 2 days
NUMBER OF REPLICATIONS: Triplicate
DETERMINATION OF CYTOTOXICITY
- Method: examination for the presence of a background lawn of non-revertant colonies - Evaluation criteria:
- No data
- Statistics:
- No data
- Key result
- 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
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- CYTOTOXICITY:
The lowest level of SDBC causing visible thinning of the background lawn of non-revertant cells was 5000 µg/plate. This was therefore selected as the top exposure level for use in the main assays. - Conclusions:
- Negative in the Ames test.
- Executive summary:
The ability of sodium dibutyldithiocarbamate (SDBC) in its manufactured form (as 47.5% aqueous solution) to induce gene mutations in bacteria was studied in Ames test with Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at test concentrations 50, 158, 500, 1580 and 5000 µg per plate (corresponding to 23.75, 75.05, 237.5, 750.5 and 2375 µg per plate for pure (anhydrous) substance), in the presence and absence of metabolic activation (Life Science Research Ltd, 1990). The study was performed in accordance with OECD Guideline 471 and EPA OTS 798.5265 and under GLP. The lowest level of SDBC causing visible thinning of the background lawn of non-revertant cells was 5000 µg/plate. The substance did not induce a statistically significant increase in the number of revertants in any strain, both with and without metabolic activation, indicating that sodium dibutyldithiocarbamate (SDBC) is not mutagenic in Ames test.
Reference
Summary of the revertant colony means:
Plate N° |
Addition (µg) |
S-9mix: + present; - absent |
Revertant colony means |
||||||||
TA98 (Test 1) |
TA98 (Test 2) |
TA100 (Test 1) |
TA100 (Test 2) |
TA1535 (Test 1) |
TA1535 (Test 2) |
TA1537 (Test 1) |
TA1537 (Test 2) |
||||
1 |
None; sterility check |
|
+ |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
SDBC sterility check |
5000 |
- |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
SDBC |
5000 |
+ |
14 |
24 |
29 |
28 |
6 |
7 |
8 |
6 |
4 |
SDBC |
1580 |
+ |
28 |
33 |
70 |
55 |
14 |
12 |
7 |
7 |
5 |
SDBC |
500 |
+ |
34 |
32 |
108 |
109 |
15 |
13 |
7 |
7 |
6 |
SDBC |
158 |
+ |
38 |
32 |
111 |
108 |
15 |
13 |
7 |
6 |
7 |
SDBC |
50 |
+ |
36 |
33 |
113 |
111 |
14 |
14 |
7 |
7 |
8 |
Distilled water |
|
+ |
37 |
32 |
110 |
110 |
13 |
13 |
8 |
7 |
9 |
SDBC |
5000 |
- |
18 |
29 |
109 |
109 |
13 |
12 |
5 |
8 |
10 |
SDBC |
1580 |
- |
29 |
34 |
109 |
111 |
14 |
14 |
8 |
7 |
11 |
SDBC |
500 |
- |
33 |
35 |
112 |
111 |
15 |
15 |
8 |
6 |
12 |
SDBC |
158 |
- |
34 |
31 |
112 |
111 |
14 |
15 |
7 |
8 |
13 |
SDBC |
50 |
- |
33 |
34 |
112 |
111 |
14 |
16 |
7 |
7 |
14 |
Distilled water |
|
- |
36 |
31 |
110 |
111 |
14 |
16 |
8 |
8 |
15 |
Benzo(a)pyrene |
|
- |
31 |
26 |
104 |
102 |
12 |
16 |
6 |
6 |
16 |
Benzo(a)pyrene |
|
+ |
260 |
393 |
590 |
470 |
846 |
494 |
218 |
171 |
17 |
2-Nitrofluorene |
|
- |
440 |
909 |
531 |
673 |
644 |
416 |
167 |
146 |
18 |
None; 10E-6 dilution of bacterial culture only |
|
- |
115 |
113 |
115 |
113 |
114 |
116 |
114 |
113 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Link to relevant study records
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- unscheduled DNA synthesis
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, UK
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 161-198 g - Route of administration:
- oral: gavage
- Vehicle:
- purified water
- Duration of treatment / exposure:
- one application of 10 mL/kg bw
- Frequency of treatment:
- n.a.
- Post exposure period:
- 2-4 h, 12-14 h
- Remarks:
- Doses / Concentrations:
400, 1000 mg/kg bw
Basis:
other: concentration in vehicle: 40, 100 mg /mL - No. of animals per sex per dose:
- 4
- Control animals:
- yes
- Positive control(s):
- 2-4 h preparation interval: 2-Acetylaminofluorene (2-AAF), 75 mg/kg bw, in corn oil,
12-14 h preparation interval: Dimethylnitrosamine (DMN), 10 mg/kg bw, in water - Tissues and cell types examined:
- - Tissue: Liver
- Type of cells: Hepatocytes - Details of tissue and slide preparation:
- - Number of animals: 4 per dose (hepatocytes were prepared from 3)
- Number of cells: 4.5×105 cells per slide - Evaluation criteria:
- - Parameters: 3H-incorporation (silver grain formation)
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- One animal (2-4h, 400 mg/kg SDDC) had a cell viability of 44%. Because of slide analysis that was considered to have no effect on the test system.
- Conclusions:
- It was concluded that SDMC does not induce UDS detectable to the liver of rats under the experimental conditions employed in the present test.
- Executive summary:
In the present in vivo genotoxicity study, SDMC (41.4% w/w aqueous solution) was tested for its ability to induce unscheduled DNA synthesis (UDS) in the livers of orally dosed male rats. The test was performed according to OECD 476 and under GLP. To determine if there were any substantial inter-sex differences in toxicity both male and female animals were tested in an initial toxicity range-finder experiment. Groups of four male rats (Han Wistar (Crl:WI (GlxIBRL/Han) BR) were treated once with the vehicle (purified water), SDDC (at 400 mg/kg or 1000 mg/kg) or the required positive control, by oral gavage, at a dose volume of 10 mL/kg. The positive controls used were 75 mg/kg 2-acetamidofluorene (2-AAF) suspended in com oil (Experiment 2) and 10 mg/kg dimethylnitrosamine (DMN) dissolved in purified water (Experiment 1). No clinical signs of toxicity were observed in Experiment 1 (2-4 hours) or Experiment 2 (12-14 hours). Approximately 2-4 hours (Experiment 1) or 12-14 hours (Experiment 2) after dosing, animals were sacrificed and their livers perfused with collagenase to provide a primary culture of hepatocytes. Cultures were made from three animals in each dose group and were treated with [3H] thymidine. Six slides from each animal were prepared with fixed hepatocytes and of these, three were dipped in photographic emulsion to prepare autoradiograms. Slides were examined microscopically after development of the emulsion and staining, and the net grain count (NNG), the number of grains present in the nucleus minus the mean number of grains in three equivalent areas of cytoplasm, was determined for each of two of the three slides, each animal and dose group. Negative (vehicle) control animals gave a group mean NNG value of less than zero with only 1% cells in repair. Group mean NNG values were increased by 2-AAF and DMN treatment to more than 10.9 and more than 50% cells found to be in repair. In this study the vehicle control NNG value was consistent with both published and historical control data, and the system was shown to be sensitive to two known DNA damaging agents requiring metabolism for their action. The assay was therefore accepted as valid. Treatment with 400 or 1000 mg/kg SDMC did not produce a group mean NNG value greater than -0.6 nor were any more than 4% cells found in repair at either dose. It was concluded that SDMC did not induce UDS detectable under the experimental conditions employed.
Reference
Table 7.6.2-B1: Net nuclear grain values and percentage of cells in repair
NNG = net nuclear grains
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
The ability of sodium dibutyldithiocarbamate (SDBC) in its manufactured form (as 47.5% aqueous solution) to induce gene mutations in bacteria was studied in Ames test with Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at test concentrations 50, 158, 500, 1580 and 5000 µg per plate (corresponding to 23.75, 75.05, 237.5, 750.5 and 2375 µg per plate for pure (anhydrous) substance), in the presence and absence of metabolic activation (Life Science Research Ltd, 1990). The study was performed in accordance with OECD Guideline 471 and EPA OTS 798.5265 and under GLP. The lowest level of SDBC causing visible thinning of the background lawn of non-revertant cells was 5000 µg/plate. The substance did not induce a statistically significant increase in the number of revertants in any strain, both with and without metabolic activation, indicating that sodium dibutyldithiocarbamate (SDBC) is not mutagenic in Ames test.
No data on the ability of SDBC to induce chromosome aberrations or gene mutations in mammalian cells were available for assessment. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. In vitro and in vivo studies on genotoxicity were available for the structural analogues of SDBC, SDMC and SDEC.
In vitro mutagenicity studies in mammalian cells
SDEC
In an in vitro mouse lymphoma assay, performed according to a procedure similar to OECD guideline 476, the ability of SDEC to cause genotoxicity was tested in mouse lymphoma L5178Y cells (McGregor, Brown et al. 1991). The exact form of SDEC (pure or in aqueous solution) 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.
SDMC
The mutagenic potential of the test substance 40% SDMC (aqueous solution) was assessed in an in vitro mammalian cell mutation assay in CHO cells conducted according to OECD TG 476 (Morry et al. 1986). The study consisted of a preliminary toxicity test.The cells were exposed to the test substance in the absence or presence of metabolic activation (S9 mix) in concentrations to 0.1 to 1 or 0.1 to 10 ug/mL, respectively, for 5 hours. Survival at the highest dose without S9 (1.0 µg/mL) indicated significant cytotoxicity. The relative cell survival is in the three highest concentrations less than 10%. With S9 the relative cell survival is in the two highest concentrations less than 10%. Exposure of the CHO cells to the test item did not result in increase of mutagenicity under the conditions of this test.
In vitro cytogenicity studies in mammalian cells
SDMC
The potential of SDMC to induce structural chromosomal aberrations in cultured mammalian cells was tested in vitro in a GLP study, performed according to OECD 473 (Jenkinson et al. 2002). Duplicate cultures of human lymphocytes, treated with the test material (SDMC 41.4% w/w aqueous solution), were evaluated for chromosome aberrations at up to four dose levels, together with vehicle and positive controls. Four treatment conditions were used for the study, ie. in Experiment 1, 4 hours in the presence of an induced rat liver homogenate metabolising system (S9), at a 1% final concentration with cell harvest after a 20-hour expression period and a 4-hour exposure in the absence of metabolic activation (S9) with a 20-hour expression period. In Experiment 2, the 4-hour exposure with addition of S9 was repeated (using a 2% final S9 concentration); whilst in the absence of metabolic activation the exposure time was increased to 24 hours. The dose levels of test material used during the course of the study were selected based on the results from a preliminary toxicity test. The test material did not induce any significant dose-related increases in the frequency of cells with aberrations, in either of two separate experiments, using a dose range that included a dose level that induced approximately 50% mitotic inhibition. The test material was shown to be non-clastogenic to human lymphocytes in vitro.
SDEC
The ability of sodium diethyldithiocarbamate (SDEC) to induce chromosome aberrations and sister chromatid exchange in Chinese hamster ovary (CHO) cells was examined (Loveday, Lugo et al. 1989). 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. In the sister chromatid exchange assay, two experiments without and one with metabolic activation (rat liver S9 fraction) 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.
In vivo genotoxicity testing
SDMC
The potential genotoxicity of SDMC was also investigated in vivo. In a mouse bone marrow micronucleus test, performed according to OECD 474 (GLP), the test material (41.4% w/w aqueous solution SDMC) was administered orally by gavage at 350, 700 or 1400 mg/kg/day to groups of six male mice killed 24 hours after the second administration. Clinical observations of eye closure and lethargy were noted in all dosed mice at levels of 700 and 1400 mg/kg/day. Additionally, abnormal breathing and two mortalities were observed in animals tested at 1400 mg/kg/day. The negative (vehicle) control was purified water and cyclophosphamide (CPA), served as the positive control. Mice treated with SDDC at all dose levels exhibited group mean ratios of PCE to NCE and frequencies of micronucleated PCE that were similar to the values for the vehicle control group and which also fell within normal historical control ranges. There were no statistically significant increases in micronucleated PCE in the test article treated groups compared to the concurrent vehicle control. Following treatment at 1400 mg/kg/day there was a notable decrease in PCE to NCE ratio compared to the vehicle control group. This is considered indicative of test article induced toxicity in the bone marrow and thus confined exposure of the target tissue to the test article. It is concluded that SDMC did not induce micronuclei in the polychromatic erythrocytes of the bone marrow of mice treated up to 1400mg/kg/day(the maximum tolerated dose for this study).
In another in vivo genotoxicity study, SDMC (41.4% w/w aqueous solution) was tested for its ability to induce unscheduled DNA synthesis (UDS) in the livers of orally dosed male rats. The test was performed according to OECD 476 and under GLP. To determine if there were any substantial inter-sex differences in toxicity both male and female animals were tested in an initial toxicity range-finder experiment. Groups of four male rats (Han Wistar (Crl:WI (GlxIBRL/Han) BR) were treated once with the vehicle (purified water), SDDC (at 400 mg/kg or 1000 mg/kg) or the required positive control, by oral gavage, at a dose volume of 10 mL/kg. The positive controls used were 75 mg/kg 2-acetamidofluorene (2-AAF) suspended in com oil (Experiment 2) and 10 mg/kg dimethylnitrosamine (DMN) dissolved in purified water (Experiment 1). No clinical signs of toxicity were observed in Experiment 1 (2-4 hours) or Experiment 2 (12-14 hours). Approximately 2-4 hours (Experiment 1) or 12-14 hours (Experiment 2) after dosing, animals were sacrificed and their livers perfused with collagenase to provide a primary culture of hepatocytes. Cultures were made from three animals in each dose group and were treated with [3H] thymidine. Six slides from each animal were prepared with fixed hepatocytes and of these, three were dipped in photographic emulsion to prepare autoradiograms. Slides were examined microscopically after development of the emulsion and staining, and the net grain count (NNG), the number of grains present in the nucleus minus the mean number of grains in three equivalent areas of cytoplasm, was determined for each of two of the three slides, each animal and dose group. Negative (vehicle) control animals gave a group mean NNG value of less than zero with only 1% cells in repair. Group mean NNG values were increased by 2-AAF and DMN treatment to more than 10.9 and more than 50% cells found to be in repair. In this study the vehicle control NNG value was consistent with both published and historical control data, and the system was shown to be sensitive to two known DNA damaging agents requiring metabolism for their action. The assay was therefore accepted as valid. Treatment with 400 or 1000 mg/kg SDMC did not produce a group mean NNG value greater than -0.6 nor were any more than 4% cells found in repair at either dose. It was concluded that SDMC did not induce UDS detectable under the experimental conditions employed.
Based on these results, sodium dibutyldithiocarbamate (SDBC) is also concluded to be non-genotoxic in vivo.
Justification for classification or non-classification
Based on the negative results in the Ames test with sodium dibutyldithiocarbamate (SDBC) and negative in vivo studies with a structural analogue, SDMC, the substance should not be classified as genotoxic, according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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