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Reaction mass of Cobaltate(3-), bis[2-[[[3-[2-[1-[[(2-chlorophenyl)amino]carbonyl]-2-(oxo-κO)propyl]diazenyl-κN1]-4-(hydroxy-κO)phenyl]sulfonyl]amino]benzoato(3-)]-, sodium (1:3) and tetrasodium bis[2-[[[3-[[1-[(2-chloroanilino)carbonyl]-2-oxopropyl]azo]-4-hydroxyphenyl]sulphonyl]amino]benzoato(3-)]cobaltate(4-)
EC number: 941-792-6 | CAS number: -
- 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
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- Nanomaterial surface chemistry
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- 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
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- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 23 September, 2002 to 17 January, 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Reaction mass of Trisodium bis[2-({[3-({1-[(2-chlorophenyl)amino]-3-(hydroxy-kO)-1-oxobut-2-en-2-yl}diazenyl-kN1)-4-(hydroxy-kO)phenyl]sulfonyl}amino)benzoato(3-)]cobaltate(3-) and Trisodium [2-({[3-({1-[(2-chlorophenyl)amino]-3-(hydroxy-kO)-1-oxobut-2-en-2-yl}diazenyl-kN1)-4-(hydroxy-kO)phenyl]sulfonyl}amino)benzoato(3-)][2-({[3-({1-[(2-chlorophenyl)amino]-3-(hydroxy-kO)-1-oxobut-2-en-2-yl}diazenyl-kN2)-4-(hydroxy-kO)phenyl]sulfonyl}amino)benzoato(3-)]cobaltate(3-)
- EC Number:
- 941-792-6
- Cas Number:
- not given
- Molecular formula:
- C46H32Cl2CoN8O14S2.3Na
- IUPAC Name:
- Reaction mass of Trisodium bis[2-({[3-({1-[(2-chlorophenyl)amino]-3-(hydroxy-kO)-1-oxobut-2-en-2-yl}diazenyl-kN1)-4-(hydroxy-kO)phenyl]sulfonyl}amino)benzoato(3-)]cobaltate(3-) and Trisodium [2-({[3-({1-[(2-chlorophenyl)amino]-3-(hydroxy-kO)-1-oxobut-2-en-2-yl}diazenyl-kN1)-4-(hydroxy-kO)phenyl]sulfonyl}amino)benzoato(3-)][2-({[3-({1-[(2-chlorophenyl)amino]-3-(hydroxy-kO)-1-oxobut-2-en-2-yl}diazenyl-kN2)-4-(hydroxy-kO)phenyl]sulfonyl}amino)benzoato(3-)]cobaltate(3-)
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: RCC Ltd., Biotechnology and Animal Breeding Division; CH-4414 Füllinsdorf
- Age at study initiation: 8 -10 weeks
- Weight at study initiation: Males mean value 37.9 g (SD ±3.1 g); Females mean value 26.5 g (SD ±3.1 g)
- Assigned to test groups randomly: Yes
- Housing: Single
- Diet (e.g. ad libitum): Pelleted standard diet, ad libitum (ALTROMIN 1324, D-32791 Lage/Lippe)
- Water (e.g. ad libitum): Tap water, ad libitum, (Gemeindewerke, D-64380 Roßdorf)
- Acclimation period: 5 d
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-72 %
- Artificial light: 6.00 a.m-6.00 p.m
IN-LIFE DATES: From: 07 October, 2002 to 02 November, 2002
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: Deionised water
- Justification for choice of solvent/vehicle: The vehicle was chosen to its relative non-toxicity for the animals.
- Volume administered: 10 mL/kg bw - Details on exposure:
- On the day of the experiment, the test substance was formulated in deionised water. The vehicle was chosen for its relative non-toxicity for the animals. All animals received a single standard volume of 10 mL/kg bw orally.
- Duration of treatment / exposure:
- Single administration
- Frequency of treatment:
- Once
- Post exposure period:
- no data
Doses / concentrationsopen allclose all
- Dose / conc.:
- 437.5 mg/kg bw/day (nominal)
- Dose / conc.:
- 875 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 750 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5/sex/group
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Positive control: Cyclophosphamide
Dissolved in: Deionized water
Dosing: 40 mg/kg bw
Route and frequency of administration: Orally, once
Volume Administered: 10 mL/kg bw
Solution prepared on day of administration. The stability of positive control at room temperature is sufficient. At 25 °C only 3.5 % of its potency is lost after 24 h.
Examinations
- Tissues and cell types examined:
- The animals were sacrificed by cervical dislocation. The femora were removed, the epiphyses were cut off and the marrow was flushed out with fetal calf serum, using a syringe. The cell suspension was centrifuged at 1500 rpm (390 x g) for 10 minutes and the supernatant was discarded. A small drop of the resuspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald/Giemsa. Cover slips were mounted with EUKITT. At least one slide was made from each bone marrow sample.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: The highest dose (1750 mg/kg bw) was estimated by a pre-experiment to be suitable.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): 24 h and 48 h after a single administration of the test substance the bone marrow cells were collected for micronuclei analysis.
METHOD OF ANALYSIS: Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives. At least 2000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and total erythrocytes was determined in the same sample and expressed in polychromatic erythrocytes per 2000 erythrocytes. The analysis was performed with coded slides. - Evaluation criteria:
- A test substance classified as mutagenic if it induces either a dose-related increase or a clear increase in the number of micronucleated polychromatic erythrocytes in a single dose group. Statistical methods (nonparametric Mann-Whitney test) will be used as an aid in evaluating the results. However, the primary point of consideration is the biological relevance of the results. A test substance that fails to produce a biological relevant increase in the number of micronucleated polychromatic erythrocytes is considered non-mutagenic in this system
- Statistics:
- no data
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- The mean number of polychromatic erythrocytes was not decreased after treatment with the test substance as compared to the mean value of PCEs of the vehicle control indicating that the test substance had no cytotoxic properties in the bone marrow. However, the urine of the treated animals was brown indicating the systemic distribution of the test substance and thus its bioavailibility. In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test substance. The mean values of micronuclei observed after treatment with the test substance were below or near to the value of the vehicle control group. 40 mg/kg bw cyclophosphamide administered orally was used as positive control which showed a statistically significant increase of induced micronucleus frequency.
Any other information on results incl. tables
Pre-experiment for toxicity:
In the first pre-experiment 4 animals (2 males, 2 females) received orally a single dose of 2000 mg/kg bw formulated in deionised water. The volume administered was 10 mL/kg bw. The animals treated with 2000 mg/kg bw expressed toxic reactions.
Toxic reactions |
Hours post-treatment |
|||||
1 h |
2-4 h |
6 h |
24 h |
30 h |
48 h |
|
Reduction of spontaneous activity |
2/2 |
2/2 |
2/2 |
1/- |
1/- |
1/- |
Abdominal position |
2/2 |
1/2 |
1/2 |
0/- |
0/- |
0/- |
Eyelid closure |
2/2 |
2/2 |
2/2 |
0/- |
0/- |
0/- |
Ruffled fur |
2/2 |
2/2 |
2/2 |
1/- |
1/- |
1/- |
Apathy |
2/2 |
1/1 |
1/2 |
0/- |
0/- |
0/- |
Urine colour |
- |
brown |
- |
brown |
- |
- |
Death |
0/0 |
0/0 |
0/0 |
1/2 |
0/0 |
0/0 |
In the second pre-experiment 4 animals (2 males, 2 females) received orally a single dose of 1500 mg/kg bw formulated in deionised water. The volume administered was 10 mL/kg bw. The animals treated with 1500 mg/kg bw expressed toxic reactions.
Toxic reactions |
Hours post-treatment |
|||||
1 h |
2-4 h |
6 h |
24 h |
30 h |
48 h |
|
Reduction of spontaneous activity |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
Abdominal position |
1/1 |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
Eyelid closure |
1/2 |
1/2 |
2/2 |
0/0 |
0/0 |
0/0 |
Ruffled fur |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
Apathy |
1/1 |
0/0 |
1/1 |
0/0 |
0/0 |
0/0 |
In the third pre-experiment 4 animals (2 males, 2 females) received orally a single dose of 1750 mg/kg bw formulated in deionised water. The volume administered was 10 mL/kg bw. The animals treated with 1750 mg/kg bw also expressed toxic reactions.
Toxic reactions |
Hours post-treatment |
|||||
1 h |
2-4 h |
6 h |
24 h |
30 h |
48 h |
|
Reduction of spontaneous activity |
2/2 |
2/2 |
2/2 |
2/2 |
2/2 |
1/1 |
Abdominal position |
1/2 |
1/2 |
2/1 |
0/0 |
0/0 |
0/0 |
Eyelid closure |
1/2 |
1/2 |
2/2 |
0/0 |
1/1 |
1/1 |
Ruffled fur |
2/2 |
2/2 |
2/2 |
1/1 |
1/1 |
1/1 |
Apathy |
1/2 |
2/2 |
2/1 |
0/0 |
1/1 |
1/1 |
On the basis of these data 1,750 mg/kg bw were estimated to be suitable.
Toxic symptoms in the main experiment: In the main experiment for the highest dose group 24 animals (12 males, 12 females) received orally a single dose of 1750 mg /kg bw formulated in deionized water. The volume administered was 10 mL/kg bw. The animals treated with 2000 mg /kg bw expressed toxic reactions.
Toxic reactions |
Hours post-treatment |
|||
1 h |
2-4 h |
6 h |
24 h |
|
Reduction of spontaneous activity |
12/10 |
12/11 |
12/12 |
3/6 |
Abdominal position |
2/0 |
2/0 |
0/3 |
0/1 |
Eyelid closure |
10/10 |
10/9 |
9/10 |
1/1 |
Ruffled fur |
12/12 |
12/12 |
12/12 |
11/11 |
Brown urine colour |
-/- |
+/+ |
-/- |
-/- |
Death |
0/0 |
0/0 |
0/0 |
1/1* |
*1 female died after the 24 h observation interval
Applicant's summary and conclusion
- Conclusions:
- The test substance did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.
- Executive summary:
The study was performed to investigate the potential of the test substance (at ca. 70-80 % purity) to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse according to OECD Guideline 474 in compliance with GLP. The substance was formulated in deionised water, which was also used as vehicle control. 24 h and 48 h after a single administration, bone marrow cells were collected for micronuclei analysis. The highest dose was chosen based on a preliminary experiment. The following dose levels were investigated:
- 24 h preparation interval: 437.5, 875 and 1750 mg/kg bw
- 48 h preparation interval: 1750 mg/kg bw
In the main experiment, 3 animals died after treatment at this dose. After treatment with the test substance, the number of PCEs was not substantially decreased as compared to the mean value of PCEs of the vehicle control, thus indicating that the test substance did not exert cytotoxic effects in the bone marrow. However, the urine of the treated animals was brown, suggesting systemic distribution of the substance and thus bioavailability. Further, there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test substance and with any dose level used. Hence, it can be concluded that the test substance did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.
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