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EC number: 228-543-0 | CAS number: 6291-65-2
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 8 November 2017 - 20 December 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Dipotassium methanedisulphonate
- EC Number:
- 228-543-0
- EC Name:
- Dipotassium methanedisulphonate
- Cas Number:
- 6291-65-2
- Molecular formula:
- CH4O6S2.2K
- IUPAC Name:
- dipotassium methanedisulphonate
- Test material form:
- solid
Constituent 1
Method
- Target gene:
- Histidine-requiring gene in Salmonella thyphimurium
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- 10% v/v S9 mix from rat liver
- Test concentrations with justification for top dose:
- 156.25, 312.5, 625, 1250, 2500 and 5000 µg/plate.
In a previous solubility test, precipitation of the test item was not observed at the tested concentration of 5000 µg/plate thus it was selected as the highest concentration to be tested for the initial toxicity-mutation test. Results from this initial toxicity test revealed that there was no positive mutagenic effect up to the tested concentration of 5000 µg/plate, thus this concentration was finally selected as the highest concentration to be tested in the confirmatory mutation test. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: distilled water
- Justification for choice of solvent/vehicle: water is recommended by OECD TG 471 and the test item was completely soluble in distilled water at 25000 µg/mL as stated in the solubility test.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- mitomycin C
- other: 2-Aminoanthracene (10 μg/plate for TA1537, TA1535 and TA102, and 5.0 µg/plate for TA98 and TA100 with metabolic activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
- Cell density at seeding (if applicable): 1–2 x10^9 bacteria/mL
DURATION
- Preincubation period: Fresh cultures for the test were prepared by inoculating frozen permanent cultures to a flask containing 10 mL of sterile nutrient broth N° 2 (Oxoid). The flasks were then incubated at 37 ± 1 °C in an orbital shaking incubator (120 rpm) for 15 h up to early stationary or late exponential phase.
- Exposure duration: 48 h incubation period at 37± 1
SELECTION AGENT (mutation assays): the lack of amino-acid in the medium. Only the mutants can grow due to their capability to synthesize the essential amino acid
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity was characterised by inhibition of the background bacterial lawn and/or reduction in the number of revertant colonies. - Rationale for test conditions:
- According to OECD TG 471
- Evaluation criteria:
- A result was considered positive if concentration-related increase over the range tested and/or a reproducible increased at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without metabolic activation system.
Strains TA1535, TA1537: Data sets were judged positive, if the increase in mean revertants at the peak of the dose response was equal to or greater than 3.0 times the mean negative control value.
Strain TA98, TA100 and TA102: Data sets were judged positive, if the increase in mean revertants at the peak of the dose response was equal to or greater than 2.0 times the mean negative control value.
A response should meet all three of the above criteria (magnitude, concentration-responsiveness, reproducibility) to be evaluated as positive. - Statistics:
- Simple linear regression analysis was performed for TA1537, TA1535, TA98, TA100 and TA102, separately, to assess the dose dependent nature of any increase in revertant colonies.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: A first stock solution up to 50000 µg/mL was prepared for the highest test concentration of 5000 µg/plate.
- Precipitation: No precipitation of the test item was observed at any concentration or tester strain used.
- Definition of acceptable cells for analysis:
All tester strain cultures exhibited sensitivity to crystal violet, demonstrating presence of the rfa wall mutation. All the tester strains demonstrated the requirement of the biotin except strain TA102 which is biotin independent. All the tester strains showed sensitivity to UV exposure except TA102 which is wild type. All the tester strains demonstrated requirement of histidine for their growth. Tester strains TA98, TA100 and TA102 exhibited resistance to ampicillin, demonstrating presence of the pKM101 plasmid. Tester strains TA102 exhibited resistance to tetracycline, demonstrating presence of the pAQ1 plasmid.
Cell densities (OD at 660 nm) of all tester strain were within the required range to produce cultures with approximately 1 - 2 x 109 bacteria/mL, demonstrating that appropriate numbers of bacteria were plated.
RANGE-FINDING/SCREENING STUDIES:
Before commencing the confirmatory mutation test (main test), test item was tested for initial toxicity-mutation test using all five tester strains of Salmonella typhimurium. The experiment was conducted for test concentrations of 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate of test item, both in the absence and presence of metabolic activation system (5% v/v S9 mix). Results revealed that there was no positive mutagenic effect in any tester strains up to the highest dose tested. Hence, 5000 µg/plate of test item was selected as the highest concentration to be tested in the confirmatory mutation test.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: see table 3 in "any other information on results incl. tables"
- Negative (solvent/vehicle) historical control data: see table 3 in "any other information on results incl. tables"
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Cytotoxicity was characterised by inhibition of the background bacterial lawn and/or reduction in the number of revertant colonies. Normal background lawn pattern without reduction in revertant colonies was observed up to the highest dose level of 5000 µg/plate both in the absence and presence of the metabolic activation system (5% v/v S9 mix) in all the tester stains.
Any other information on results incl. tables
Table 1: Mean Count of His+ Revertant Colonies in Negative Control, Positive Controls and Treatment Plates in the Absence of Metabolic Activation (Confirmatory Mutation Test)
Concentration of Test Item (µg/plate) |
His+Revertant Colonies/Plate [Absence of Metabolic Activation] |
|||||||||
TA1537 |
TA1535 |
TA98 |
TA100 |
TA102 |
||||||
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
|
NC (DW) |
8.00 |
3.00 |
14.67 |
2.08 |
19.00 |
3.00 |
133.33 |
8.02 |
233.33 |
9.61 |
156.25 |
8.67 |
3.51 |
15.67 |
4.51 |
17.33 |
2.52 |
134.67 |
7.57 |
232.67 |
8.02 |
312.5 |
8.33 |
2.52 |
14.33 |
5.51 |
18.67 |
5.51 |
132.67 |
4.93 |
234.00 |
7.55 |
625 |
5.33 |
2.52 |
15.67 |
2.08 |
18.67 |
4.04 |
131.67 |
11.02 |
235.33 |
8.08 |
1250 |
8.00 |
2.65 |
15.67 |
3.51 |
19.33 |
2.08 |
135.67 |
7.09 |
230.33 |
10.07 |
2500 |
9.33 |
3.79 |
13.67 |
3.06 |
19.67 |
7.64 |
133.67 |
9.29 |
232.67 |
7.64 |
5000 |
8.00 |
1.00 |
15.67 |
4.51 |
19.33 |
6.11 |
133.33 |
10.21 |
233.33 |
6.66 |
PC |
228.00 |
78.25 |
378.00 |
113.42 |
552.67 |
245.50 |
932.67 |
58.23 |
961.33 |
98.59 |
2Aa |
- |
- |
- |
- |
- |
- |
131.67 |
8.02 |
- |
- |
Keys: SD = Standard Deviation, NC = Negative Control, DW = Distilled Water, PC = Positive Control {TA1537 = 9-Aminoacridine Hydrochloride Monohydrate (75 µg/plate), TA1535 = Sodium Azide (0.5 µg/plate), TA98 = 2-Nitrofluorene (7.5 µg/plate), TA100 = Sodium Azide (5 µg/plate), TA102 = Mitomycin-C (0.5 µg/plate)}, 2-Aa = 2-Aminoanthracene (5 µg/plate for TA100), - = Not Applicable, Test Item = Dipotassium methanedisulphonate.
Table 2: Mean Count of His+ Revertant Colonies in Negative Control, Positive Control and Treatment Plates in the Presence of Metabolic Activation (Confirmatory Mutation Test)
Concentration of Test Item (µg/plate) |
His+Revertant Colonies/Plate [Presence of Metabolic Activation (10% v/v S9 mix)] |
|||||||||
TA1537 |
TA1535 |
TA98 |
TA100 |
TA102 |
||||||
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
|
NC (DW) |
8.00 |
2.65 |
15.67 |
4.04 |
20.67 |
4.04 |
137.00 |
12.12 |
236.00 |
12.00 |
156.25 |
7.00 |
3.00 |
15.33 |
2.31 |
20.33 |
4.73 |
135.33 |
18.58 |
238.33 |
6.11 |
312.5 |
9.33 |
2.52 |
16.00 |
3.00 |
21.00 |
5.29 |
138.33 |
7.51 |
232.67 |
10.69 |
625 |
8.00 |
3.61 |
14.33 |
2.52 |
20.33 |
2.52 |
135.33 |
6.66 |
236.33 |
11.59 |
1250 |
8.00 |
2.65 |
16.67 |
5.13 |
21.33 |
4.04 |
137.00 |
13.11 |
235.00 |
12.29 |
2500 |
8.67 |
4.16 |
15.00 |
4.00 |
21.00 |
4.58 |
136.67 |
15.53 |
235.67 |
5.51 |
5000 |
9.33 |
2.08 |
16.67 |
5.03 |
21.33 |
4.73 |
138.67 |
15.31 |
236.67 |
7.77 |
PC-2Aa |
310.67 |
164.89 |
496.00 |
157.55 |
785.33 |
89.19 |
858.00 |
40.58 |
964.00 |
152.56 |
Keys: SD = Standard Deviation, NC = Negative Control, DW = Distilled Water, PC = Positive Control, 2Aa = 2-Aminoanthracene (10 µg/plate for TA1537, TA1535, TA102 and 5 µg/plate for TA98 and TA100), Test Item = Dipotassium methanedisulphonate.
Table 3: Historical Control Data (Data of 112 studies conducted at JRF during July 2016 to July 2017)
Negative Control (Distilled Water) without S9 Mix |
|||||||
Strain |
TA1537 |
TA1535 |
TA98 |
TA100 |
TA102 |
E. coliWP2uvrA |
E. coliWP2uvrA (pKM101) |
Mean Revertants per Plate |
8.50 |
18.46 |
22.73 |
130.74 |
229.33 |
28.80 |
119.75 |
Standard Deviation |
2.87 |
4.65 |
5.00 |
11.15 |
11.69 |
4.09 |
7.76 |
Maximum |
15 |
29 |
33 |
161 |
269 |
33 |
135 |
Minimum |
2 |
9 |
10 |
103 |
203 |
24 |
108 |
Negative Control (Distilled Water) with S9 Mix |
|||||||
Mean Revertants per Plate |
9.32 |
20.08 |
24.13 |
133.63 |
233.14 |
30.00 |
123.80 |
Standard Deviation |
2.91 |
4.87 |
5.47 |
10.66 |
12.22 |
5.24 |
8.90 |
Maximum |
16 |
33 |
36 |
157 |
268 |
37 |
143 |
Minimum |
3 |
10 |
13 |
105 |
205 |
25 |
112 |
Negative Control (Dimethyl Sulfoxide) without S9 Mix |
|||||||
Mean Revertants per Plate |
8.40 |
18.37 |
22.79 |
131.37 |
228.89 |
27.33 |
115.16 |
Standard Deviation |
2.73 |
4.44 |
4.92 |
10.65 |
12.48 |
4.86 |
7.68 |
Maximum |
13 |
28 |
34 |
155 |
277 |
35 |
131 |
Minimum |
3 |
8 |
13 |
107 |
202 |
20 |
100 |
Negative Control (Dimethyl Sulfoxide) with S9 Mix |
|||||||
Mean Revertants per Plate |
8.96 |
20.03 |
24.24 |
134.50 |
232.55 |
29.67 |
119.24 |
Standard Deviation |
3.02 |
4.97 |
5.43 |
10.53 |
13.12 |
5.81 |
8.04 |
Maximum |
15 |
31 |
36 |
159 |
266 |
40 |
136 |
Minimum |
3 |
8 |
12 |
112 |
156 |
22 |
103 |
Positive Control without S9 Mix |
|||||||
Mean Revertants per Plate |
274.27 |
376.70 |
542.14 |
880.92 |
1058.59 |
461.35 |
925.09 |
Standard Deviation |
94.89 |
113.61 |
148.27 |
175.36 |
152.48 |
143.11 |
195.70 |
Maximum |
1015 |
836 |
1062 |
1333 |
1543 |
794 |
1235 |
Minimum |
75 |
134 |
217 |
417 |
427 |
281 |
417 |
Positive Control with S9 Mix |
|||||||
Mean Revertants per Plate |
300.52 |
419.02 |
671.47 |
968.94 |
1088.70 |
538.45 |
993.91 |
Standard Deviation |
98.11 |
122.05 |
171.10 |
158.04 |
154.86 |
126.44 |
220.14 |
Maximum |
682 |
802 |
1463 |
1441 |
1581 |
753 |
1289 |
Minimum |
73 |
191 |
283 |
577 |
586 |
238 |
389 |
Negative control:
-Distilled Water
Positive controls in the absence of metabolic activation:
-TA1537 = 9-Aminoacridine Hydrochloride Monohydrate (75 µg/plate), TA1535 = Sodium Azide (0.5 µg/plate), TA98 = 2-Nitrofluorene (7.5 µg/plate), TA100 = Sodium Azide (5 µg/plate), TA102 = Mitomycin-C (0.5 µg/plate).
Positive controls in the presence of metabolic activation:
-2Aa = 2-Aminoanthracene (10 µg/plate for TA1537, TA1535, TA102 and 5 µg/plate for TA98 and TA100)
Applicant's summary and conclusion
- Conclusions:
- Under the experimental conditions reported, the test substance is non-mutagenic to any of the five strains of Salmonella typhimurium (i.e., TA1537, TA1535, TA98, TA100 and TA102).
- Executive summary:
The test item was tested for potential mutagenic activity using the Bacterial Reverse Mutation Assay according to OECD Guideline 471 (GLP study). The experiments were carried out using Salmonella typhimurium strains TA1537, TA1535, TA98, TA100 and TA102 in the presence and absence of metabolic activation (S9 mix prepared from the livers of rats). The test item was dissolved in distilled water, based on its solubility. In the initial toxicity-mutation test the bacterial cultures were exposed to test item at 8 concentrations (two plates/concentration) between 1.5 and 5000 µg/plate . Normal background lawn pattern was observed up to the highest dose in all tester strains, no mutagenic effect was observed both in the absence and presence of the metabolic activation system (5% v/v S9 mix) in all the tester strains. In the main test, the cultures were exposed to test item at 6 concentrations (three plates/concentration) between 156.25 and 5000 µg/plate both in the absence and presence (10% v/v S9 mix) of metabolic activation. All the values for the negative control were within historical control ranges of the laboratory and positive controls showed an increase in the number of revertant colonies. All validity criteria were met. No positive effect was obtained in the examined bacterial strains with and without metabolic activation system.
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