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EC number: 205-286-2 | CAS number: 137-26-8
- 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:
- 19 Jan - 26 Feb 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted in 2020
- Deviations:
- yes
- Remarks:
- Missing strain for AT reversion site (S. thyphimurium TA 102 or E.coli WP2)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Thiram
- EC Number:
- 205-286-2
- EC Name:
- Thiram
- Cas Number:
- 137-26-8
- Molecular formula:
- C6H12N2S4
- IUPAC Name:
- thiram
Constituent 1
Method
- Target gene:
- His operon
Species / strain
- Species / strain / cell type:
- bacteria, other: TA 98, 100, 1535, 1538 and 1537
- Additional strain / cell type characteristics:
- other: His auxotrophy, defective DNA repair activity (delta uvrB) and defective LPS barrier (rfa) Ampicillin resistance (TA 98 and TA 100 only)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of Wistar rats which received a single injection of 500 mg/kg bw Aroclor 1254 in olive oil 5 days before sacrifice.
The protein concentration of the S9 preparation was usually between 20 and 45 mg/mL.
The S9 fraction was mixed with cofactors to final concentrations of: 8 mM MgCI2, 33 mM KCI, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-ortho-phosphate buffer (pH 7.4).
S9 fraction was thawed and mixed with S9 cofactor solution, to result in a final concentration of approx. 5.6 % v/v in the S9 mix. Each batch of S9 was routinely tested for its capability to activate the known mutagen 2-aminoanthracene in the Ames test. - Test concentrations with justification for top dose:
- The standard plate incorporation assay was performed using 1, 10, 33.3, 100, 333.3, 666.6 and 1000 µg/plate of the test item with S9 mix using Salmonella strains TA 98, TA 100, TA 1535, TA 1538 and TA 1537.
Without S9 mix Salmonella strains TA 100, TA 1535,TA 1538 and TA 1537 were used in the presence of 1, 3.3, 10, 33.3, 66.6 and 100 µg test substance/plate.
Strain TA 98 was tested with 10, 33.3, 100, 333.3, 666.6 and 1000 µg test substance/plate, without S9 mix.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- other: 4-nitro-o-phenylene-diamine, 4-NOPD, TA 1537, TA 1538, TA 98, 50 μg/plate in DMSO; - S9 mix, 2-aminoanthracene, 2-AA, TA 1535, TA 1537, TA 1538, TA 98, TA 100, 10 µg/plate in DMSO, + S9 mix
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicates
- Number of independent experiments: 2 (with and without metabolic activation, plus a pre-test for strains TA 98 and TA 100)
METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar (plate incorporation)
TREATMENT AND HARVEST SCHEDULE:
- Exposure duration/duration of treatment: 72 h
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: background growth inhibition - Rationale for test conditions:
- A pre-experiment for testing the toxicity of the test article was performed with strains TA 98 and TA 100. 8 concentrations were tested for toxicity and mutagenicity with each 3 plates.
- Evaluation criteria:
- A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 100) or thrice (strains TA 1535, TA 1537, TA 1538, TA 98) the colony count of the corresponding solvent control is observed. Also, a significant dose-dependent increase in the number of revertants is regarded as an indication of possibly existing mutagenic potential.
Acceptability:
The Salmonella typhimurium reverse mutation assay is considered acceptable if it meets the following criteria:
- regular background growth in the negative and solvent control
- the spontaneous reversion rates in the negative and solvent control are in the range of the historical data - Statistics:
- No statisitcal analysis was performed.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxic effects occurred with and without metabolic activation at 1000 µg/plate (exp.II)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxic effects occurred with and without metabolic activation at 1000 µg/plate (exp.II).
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxic effects occurred at 333.3 and 1000µg/plate (exp.I) with and without metabolic activation.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- dose-dependent and significant increase in revertant colony numbers with and without metabolic activation
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- normal background growth up to 1000 µg/plate with S9 mix and up to 100 µg/plate in the absence of metabolic activation.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- dose-dependent and significant increase in revertant colony numbers with and without metabolic activation.
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- normal background growth up to 1000 µg/plate with S9 mix and up to 100 µg/plate in the absence of metabolic activation.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
In the pre-experiment the concentration range of the test item was 1 – 5000 μg/plate and only in strains TA 98 and 100. Genotoxicity was not observed up to the highest concentration tested. At 5000 µg/mL, no spontanous revertants occurred. Data can be found in Attachment 1 in the attached background material.
STUDY RESULTS
The test material produced a dose-dependent and significant increase in revertant colony numbers observed in strains TA1535 and TA100 in the two experiments performed. Signs of toxicity with and without metabolic activation. With and without S9 mix, toxic effects occurred in strains TA98 at 333.3 and 1000µg/plate (exp.I) and in the strains TA1537 and TA1538 at 1000 µg/plate (exp.II). With metabolic activation toxic effects occurred in strains TA1537 (exp.I) and TA100 (exp.I and II) at 1000 µg/plate. Strains TA1535, TA1537, TA1538 and TA100 showed normal background growth up to 1000 µg/plate with S9 mix and up to 100 µg/plate in the absence of metabolic activation.
For results of both experiment I and experiment II as well as the pre-experiment, please refer to the attached background material
(Attachment 2) under "Attached background material"
HISTORICAL CONTROL DATA
- Positive historical control data: no
- Negative (solvent/vehicle) historical control data: yes, can be found in Attachment 3 in the attached background material.
Any other information on results incl. tables
Table 1: Revertant colonies mean from three plates with and without metabolic activation
Treatment |
Conc. [µg/plate] |
S9 mix |
TA 1535 Exp I/ ExpII |
TA 1537 Exp I/ ExpII |
TA 1538 Exp I/ ExpII |
TA 98 Exp I/ ExpII |
TA 100 Exp I/ ExpII |
Negative control |
|
- |
22 ; 9 |
10 ; 9 |
18 ; 12 |
19 ; 19 |
95 ; 77 |
Solvent controlA |
|
- |
18 ;16 |
6 ; 7 |
12 ; 12 |
18 ; 20 |
89 ; 75 |
test substance |
1.0 |
- |
27 ; 18 |
9 ; 15 |
10 ; 14 |
- ; - |
107 ; 104 |
|
3.3 |
- |
17; 22 |
11 ; 8 |
15 ; 15 |
- ; - |
132 ; 109 |
|
10.0 |
- |
33; 23 |
16 ; 17 |
11 ; 17 |
25 ; 32 |
205 ; 147 |
|
33.3 |
- |
54 ;41 |
12 ; 17 |
12 ; 15 |
33 ; 31 |
277 ; 220 |
|
66.6 |
- |
56; 53 |
12 ; 16 |
16 ; 14 |
- ; - |
271 ; 274 |
|
100.0 |
- |
44; 51 |
12 ; 12 |
14 ; 21 |
34 ; 31 |
368 ; 256 |
|
333.3 |
- |
|
|
|
8 ; 33 |
|
|
666.6 |
- |
|
|
|
7 ; 16 |
|
|
1000.0 |
- |
|
|
|
1 ; 12 |
|
Positive controlB |
|
- |
133 ; 1100 |
305 ; 220 |
2594 ; 2421 |
2031 ; 170 |
1299 ; 1069 |
Negative control |
|
+ |
11 ; 11 |
10 ; 13 |
16 ; 13 |
33 ; 31 |
104 ; 87 |
Solvent controlA |
|
+ |
11 ; 12 |
11 ; 13 |
18 ; 13 |
32 ; 29 |
89 ; 92 |
test substance |
1.0 |
+ |
20 ; 14 |
9 ; 12 |
17 ; 13 |
31 ; 30 |
95 ; 98 |
|
10.0 |
+ |
23 ; 27 |
11 ; 13 |
20 ; 15 |
38 ; 28 |
145 ; 187 |
|
33.3 |
+ |
52 ; 44 |
14 ; 18 |
12 ; 16 |
35 ; 40 |
220 ; 269 |
|
100.0 |
+ |
70 ; 54 |
19 ; 11 |
16 ; 19 |
40 ;42 |
298 ; 293 |
|
333.3 |
+ |
45 ; 34 |
11 ; 11 |
10 ; 17 |
33 ; 27 |
247 ; 304 |
|
666.6 |
+ |
53 ; 39 |
12 ; 11 |
15 ; 9 |
47 ;45 |
247 ; 266 |
|
1000.0 |
+ |
37 ; 26 |
0 ; 4 |
11 ; 3 |
31 ; 43 |
0 ; 0 |
Positive controlB |
|
+ |
507 ; 109 |
414 ; 89 |
2243 ; 152 |
2604 ; 1672 |
2564 ; 837 |
ADMSO,B2-aminoanthracene,SD - Standard deviation |
|
|
Applicant's summary and conclusion
- Conclusions:
- The study was performed according to OECD guideline 471 and compliant with GLP. Under the conditions of this study, the test substance induced point mutations by base pair changes in the genome of the strains TA1535 and TA100 with and without metabolic activation.
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