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EC number: 286-304-6 | CAS number: 85204-10-0
- 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 cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: chromosome aberration test in vitro
Test material
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 2 mM L-glutamine, 1 (v/v) % Antibiotic-antimycotic solution (standard content: 10000 NE/mL penicillin, 10 mg/mL streptomycin and 25 μg/mL amphotericin-B) and 10 (v/v) % heat-inactivated fetal bovine serum (DMEM-10, culture medium). During the treatments, the serum content of the medium was reduced to 5 (v/v) % (DMEM-5).
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix ( induced rat liver by Phenobarbital (PB) and β-naphthoflavone (BNF))
- Test concentrations with justification for top dose:
- Assay 1: (3 hours)
without S9-mix: 1500, 1000, 750, 500, 250, 120, 62.5 and 31.25 μg/mL
with S9-mix: 3000, 2500, 2000, 1000, 500, 250 and 125 μg/mL
Assay 2:
20 hours, without S9-mix: 3000, 2500, 2000, 1500, 1000, 500, 250 and 125 μg/mL
3 hours, with S9-mix: 1500, 1000, 750, 500, 250, 120, 62.5 and 31.25 μg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: distilled water
- Justification for choice of solvent/vehicle: appropriate for formulation and its dilution; compatible to the test system
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without S9-mix; dissolved in DMEM; 0.4 μL/mL (28-hour harvesting time) or 1.0 μL/mL (20-hour harvesting time) [
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with S9-mix; dissolved in 0,9% NaCl; 6.0 μg/mL
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration:3 and 20 hours
- Fixation time (start of exposure up to harvest of cells): 20 and 28 hours
SPINDLE INHIBITOR (cytogenetic assays): Colchicine (0.2 μg/mL)
STAIN (for cytogenetic assays): 5 % Giemsa solution
NUMBER OF CELLS EVALUATED: 200 cells (metaphases)/dose
DETERMINATION OF CYTOTOXICITY
- Method: determination of cell concentration by use of a haemocytometer
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes - Evaluation criteria:
- - Increases in the frequency of metaphases with aberrant chromosomes are observed at one or more test concentrations (only data without gaps will be considered).
- The increases are reproducible between replicate cultures and between tests (when treatment conditions were the same).
- The increases are statistically significant.
- The increases are not associated with large changes in pH or osmolarity of the treated cultures. - Statistics:
- For statistical analysis, Fisher’s exact test was used. The parameter evaluated for statistical analysis was the number of cells with one or more chromosomal aberrations excluding gaps.
Results and discussion
Test results
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- Assay 1: without S9-mix: > 500 μg/mL; with S9-mix: > 250 μg/mL. Assay 2: No significant increase in the number of cells with structural chromosome aberrations with or without S9-mix.
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- without S9-mix: > 500 (250) μg/mL; with S9-mix: > 2000 (1500) μg/mL, in brackets values of Assay 2
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
Table 1: Summarized results of the concentration selection cytotoxicity assays
|
Dose(μg/mL) |
Testgroup without S9-mix Relative survival (%) (Assay A/B) |
Testgroup with S9-mix (Assay A/B) |
Untreated control |
|
84/127 |
125/101 |
Vehicle control 1%(v/v) Distilled water |
|
100/100 |
100/100 |
Vehicle control 2% v/v Distilled water |
|
100/100 |
100/100 |
WS400402
|
5000 |
0/0 |
2/0 |
2500 |
0/0 |
41/18 |
|
1250 |
7/4 |
73/63 |
|
625 |
29/21 |
86/91 |
|
312,5 |
67/53 |
88/94 |
|
156,25 |
74/95 |
107/99 |
|
78,13 |
76/99 |
112/101 |
|
39,06 |
80/107 |
100/96 |
Time of Treatment/Sampling: 3h/20h
No insolubility of test material was detected at the end of the treatment period in the final treatment medium; there were no large changes in pH and osmolality either.
Table 2: Cytotoxicity results of the main experiments
|
Dose(μg/mL) |
Testgroup without S9-mix Rel. survival (%) Assay 1 3h/20h* |
Testgroup without S9-mix Rel. survival (%) Assay 2 20h/28h* |
Dose(μg/mL) |
Testgroup with S9-mix Rel. survival (%) Assay 1 3h/20h* |
Testgroup with S9-mix Assay 2 3h/28h* |
|
Vehicle control 2% v/v Distilled water |
|
100 |
100 |
|
100 |
100 |
|
WS400402
|
1500 |
0 |
0 |
3000 |
23 |
11 |
|
1000 |
2 |
1 |
2500 |
25 |
17 |
||
750 |
13 |
3 |
2000 |
40 |
48 |
||
500 |
37 |
12 |
1500 |
- |
36 |
||
250 |
73 |
41 |
1000 |
62 |
59 |
||
125 |
97 |
65 |
500 |
76 |
83 |
||
62,5 |
100 |
89 |
250 |
81 |
97 |
||
31,25 |
101 |
80 |
125 |
95 |
90 |
||
Positive control
|
- |
1μL/mL EMS 80 |
1μL/mL EMS 48 |
- |
51 |
6 μg/mL CP 52 |
*Treatment time/sampling
Table 3: Summary table of Chromosome Aberration Assay 1
Concentration (μg/mL) |
Time of Treatment |
Relative # Survival (%) |
Mean% aberrant cells### |
WS400402without metabolic activation (-S9) |
|||
Vehicle(solvent)control |
3h/20h |
100 |
1.0 |
1500 |
3h/20h |
0 |
NE |
1000 |
3h/20h |
2 |
NE |
750 |
3h/20h |
13 |
NE |
500 |
3h/20h |
37 |
18.1*** |
250 |
3h/20h |
73 |
2.0 |
125 |
3h/20h |
97 |
3.0 |
62.5 |
3h/20h |
100 |
NE |
31.25 |
3h/20h |
101 |
NE |
Positive control |
3h/20h |
80 |
12.4*** |
WS400402with metabolic activation (+S9) |
|||
Vehicle(solvent)control |
3h/20h |
100 |
2.0 |
3000 |
3h/20h |
23 |
NE |
2500 |
3h/20h |
25 |
NE |
2000 |
3h/20h |
40 |
60.0*** |
1000 |
3h/20h |
62 |
12.3*** |
500 |
3h/20h |
76 |
3.0 |
250 |
3h/20h |
81 |
11.0** |
125 |
3h/20h |
95 |
NE |
Positive control |
3h/20h |
51 |
96.8*** |
Vehicle (solvent) control: 2% (v/v) Distilled water Positive control (-S9):Ethyl methanesulfonate,1µL/mLPositive control (+S9): Cyclophosphamide, 6µg/mL
NE: notevaluated
#: compared to the vehicle (solvent) control
##:in the final treatment medium at the end of the treatment
###:excluding gaps
**: p<0.01comparing numbers of aberrant cells excluding gaps with corresponding vehicle (solvent)control
***:p<0.001comparing numbers of aberrant cells excluding gaps with corresponding vehicle (solvent)control
Table 4: Summary table of Chromosome Aberration Assay 2
Concentation (μg/mL) |
Time of Treatment/Sampling |
Relative # Survival (%) |
Mean% aberrant cells### |
WS400402without metabolic activation (-S9) |
|||
Vehicle (solvent) control |
20h/28h |
100 |
2.5 |
1500 |
20h/28h |
0 |
NE |
1000 |
20h/28h |
1 |
NE |
750 |
20h/28h |
3 |
NE |
500 |
20h/28h |
12 |
NE |
250 |
20h/28h |
41 |
1.5 |
125
|
20h/28h |
65 |
2.0 |
62.5 |
20h/28h |
89 |
1.0 |
31.25 |
20h/28h |
80 |
NE |
Positive control |
20h/28h |
48 |
50.8*** |
WS400402with metabolic activation (+S9) |
|||
Vehicle(solvent)control |
3h/28h |
100 |
3.0 |
3000 |
3h/28h |
11 |
NE |
2500 |
3h/28h |
17 |
NE |
2000 |
3h/28h |
28 |
NE |
1500 |
3h/28h |
36 |
7.0 |
1000 |
3h/28h |
59 |
4.5 |
500 |
3h/28h |
83 |
4.0 |
250 |
3h/28h |
97 |
NE |
125 |
3h/28h |
90 |
NE |
Positive control |
3h/28h |
52 |
68.2*** |
Vehicle (solvent) control: 2% (v/v) Distilled water
Positive control (-S9): Ethyl methanesulfonate,0.4µL/mLPositive control (+S9):Cyclophosphamide,6µg/mL
NE: not evaluated
#:compared to the vehicle (solvent)control
##:in the final treatment medium at the end of the treatmentment
###:excluding gaps
***:p<0.001comparing numbers of aberrant cells excluding gaps with corresponding vehicle (solvent) control.
None of the treatment doses caused a significant increase in the number of cells with structural chromosome aberrations in Assay 2 with or without metabolic activation although a dose related increase was observed across all the concentrations tested with metabolic activation.
Polyploid and endoreduplicated metaphases
Polyploid metaphases (1-4) were found in some cases in the vehicle (solvent) control, positive control or test material treated samples.No endoreduplicated metaphases were found in the two main tests except of one sample (in Assay 2 at 1500 μg/mL concentration with metabolic activation two endoreduplicated metaphases were found, all other values: 0).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
positive
In conclusion, WS400402 test item induced a significant level of chromosome aberrations in the performed experiments with and without metabolic activation. Therefore, WS400402 is considered clastogenic in this test system.
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