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EC number: 433-180-8 | 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
- 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 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:
- 1999-05-03 to 1999-05-20
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed according to GLP and guidelines
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Details on test material:
- -Name of test material (as cited in study report): Reaktiv-Orange DYPR934
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Species: Mouse
Strain: Hsd Win:NMRI
- Source: ORIGINE (supplier) of animals: Harlan Winkelmann GmbH, Gartenstrasse 27, 33178 Borchen
- Age at study initiation: male/female animals approx. 7 weeks
- Weight at study initiation: MALE ANIMALS: mean = 32.3 g (= 100 %)
min = 29 g (-10.2 %)
max= 35 g (+8.4 %)
n = 15
FEMALE ANIMALS: mean =26.7 g (= 100 %)
min = 24 g (-10.1 %)
max= 32g (+19.9 %)
n=15
- Assigned to test groups randomly: [yes, under following basis:] randomization schemes 1999.0149 and 1999.0150
ANIMAL MAINTENANCE:
In fully air conditioned rooms in macrolon cages type 3 (five animals per cage) on soft wood granulate.
Food: rat/mice diet ssniff ® R/M-H (V1534) ad libitum
- Fasting period before study:
- Housing:
ANIMAL IDENTIFICATION: fur marking with KMn04 and cage numbering
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): Tap water in plastic bottles, ad libitum.
- Acclimation period: 5 days under study conditions
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours daily
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Deionized water.
- Amount of vehicle (if gavage or dermal): The vehicle was administered in the negative control groups (twice at interval of 24 hours orally by gavage at a dose of 2000 mg per kg body weight.) - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test compound was dissolved in deionized water and was given twice at an interval of 24 hours as an orally dose of 2000 mg/kg body weight.
In a preliminary dose range finding study, oral administration of 2000 mg Reaktiv-Orange DYPR 934 per kg body weight did not cause any toxic effects in male and female
1 st dose: 2000 mg Reaktiv-Orange DYPR 934 per kg body weight
Observation period: 1999-04-20 to 1999-04-28
Number of animals used: 3 males and 3 females
DIET PREPARATION
- FREQUENCY OF ADMINISTRATIONS: twice at interval of 24 hours
FORMULATION OF TEST COMPOUND: On the days of administration the test substance was dissolved in deionized water at appropriate concentration.
A magnetic stirrer was used to keep the preparation homogeneous until dosing had been completed.
FORMULATION OF REFERENCE COMPOUND: Cyclophosphamide (CPA) dissolved in distilled water on the second day of experiment; final concentration 0.5 % (w/v)
FORMULATION OF TEST COMPOUND: On the days of administration the test substance was dissolved in deionized water at appropriate concentration.
A magnetic stirrer was used to keep the preparation homogeneous until dosing had been completed.
FORMULATION OF REFERENCE COMPOUND: Cyclophosphamide (CPA) dissolved in distilled water on the second day of experiment; final concentration 0.5 % (w/v) - Duration of treatment / exposure:
- 1 day (twice at an interval of 24 hours)
- Frequency of treatment:
- Once
- Post exposure period:
- Test item group animals dosed at 2000 mg/kg body weight were sacrificed 24 hrs following dosing.
Vehicle control animals were sacrificed 24 hrs following dosing.
Positive control animals were sacrificed 24 hrs following dosing.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2000 mg/kg
Basis:
nominal in water
- No. of animals per sex per dose:
- Male: 2000 mg/kg; No. of animals: 5; Sacrifice time: 24 hours
Female: 2000 mg/kg; No. of animals: 5; Sacrifice times: 24 hours - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide (=Endoxan®)
- Justification for choice of positive control(s): produce micronuclei in vivo at exposure levels expected to give a detectable increase over background.
- Route of administration: oral /gavage
- Dose(s) / concentration(s): 50 mg/kg body weight
Examinations
- Tissues and cell types examined:
- The animals were examined for clinical signs of toxicity after dosing. Femural bone marrow was prepared from all control and dose group animals at 24 hr post dosing in animals receiving the high 2000 mg/kg body weight dose.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Preliminary experiment: Preliminary studies were conducted to determine the highest administrable non lethal dose level up to the limit dose of 2000 mg body weight according to the OECD
PREPARATION AND STAINING
Animals were killed by carbon dioxide asphyxiation 24 hours after dosing. For each animal, about 3 mL fetal bovine serum was poured into a centrifuge tube. Both femora were removed and the bones freed of muscle tissue. The proximal ends of the femora were opened and the bone marrow flushed into the centrifuge tube. A suspension was formed. The mixture was then centrifuged for 5 minutes at approx. 1200 rpm, after which almost all the supernatant was discarded. One drop of the thoroughly mixed sediment was smeared onto a cleaned slide, identified by project code and animal number and air-dried for about 12 hours.
STAINING:
Staining was performed as follows:
-5 minutes in methanol
-5 minutes in May-Grünwald’s solution
-brief rinsing in twice distilled water
-10 minutes staining in 1 part Giemsa solution to 6 parts buffer solution, pH 7.2 (Weise)
-rinsing in distilled water
-drying
-coating with Entellan® - Evaluation criteria:
Evaluation:
2000 polychromatic erythrocytes were counted for each mouse. The number of cells with micronuclei was recorded, not the number of individual micronuclei. In addition, the ratio of polychromatic erythrocytes to 200 total erythrocytes was determined. Main parameter for the statistical analysis, i.e. validity assessment of the study and mutagenicity of the substance, was the proportion of polychromatic erythrocytes with micronuclei out of 2000 counted erythrocytes. All bone marrow smears for evaluation were coded to ensure that the group from which they were taken remained unknown to the investigator.
A one-sided Wilcoxon Test was evaluated to check the validity of the study. The study was considered as valid in case the proportion of polychromatic erythrocytes with micronuclei in the positive control was significantly higher in the negative control (p = 0.05).
If the validity of the study has been shown the following sequential test procedure for the examination of the mutagenicity was applied: Based on a monotone -dose-relationship one-sided Wilcoxon tests were performed starting with the highest dose group. These tests were performed with a multiple significance of 5 %.
- Statistics:
- Biological and statistical significances.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Observations: All animals survived after treatment. No signs of toxicity; but orange discolored feces and urine were observed up to the end of study.
Any other information on results incl. tables
Summary tables and Statistics: Test compound: Reaktiv-Orange DYPR 934 |
|||||||||
Sex |
Dose Mg/kg b.w. |
Killing time
|
Number of animals |
Poly counted |
Poly/Ery Mean |
Poly/Ery SD Mean |
Poly with MN Mean |
Poly with MN [%] Mean |
Poly with MN SD Mean |
male |
0-Control |
24h |
5 |
2000 |
0.46 |
0.08 |
1.6 |
0.08 |
0.07 |
male |
2000 |
24h |
5 |
2000 |
0.45 |
0.06 |
1.0 |
0.05 |
0.05 |
male |
50-Endoxan®
|
24h |
5 |
2000 |
0.43 |
0.06 |
87.0 |
4.35 |
1.65 |
female |
0-Control |
24h |
5 |
2000 |
0.44 |
0.13 |
2.2 |
0.11 |
0.07 |
female |
2000 |
24h |
5 |
2000 |
0.37 |
0.08 |
3.2 |
0.18 |
0.05 |
female |
50-Endoxan®
|
24h |
5 |
2000 |
0.42 |
0.09 |
63.8 |
3.19 |
0.88 |
|
Summary tables and Statistics: Test compound: Reaktiv-Orange DYPR 934 |
||||||||||
Sex |
Dose Mg/kg b.w. |
Killing time
|
Number of animals |
Poly counted |
Poly/Ery Mean |
Poly/Ery SD Mean |
Poly with MN Mean |
Poly with MN [%] Mean |
Poly with MN SD Mean |
Mutagenetic Index |
|
pooled |
0-Control |
24h |
10 |
2000 |
0.45 |
0.10 |
1.90 |
0.1 |
0.07 |
0.07 Mutagenetic Index: 1.0 |
|
pooled |
2000 |
24h |
10 |
2000 |
0.41 |
0.08 |
2.10 |
0.1 |
0.1 |
0.08 Mutagenetic Index: 1.1 |
|
pooled |
50-Endoxan®
|
24h |
10 |
2000 |
0.42 |
0.07 |
75.40 (significant difference from control (p<0.05) |
3.8 |
3.8 |
1.39 Mutagenetic Index: 39.7 |
|
Control= vehicle (deionized water)
A cross comparaison of individual data and pooled data may show discrepancies since the values are rounde.TABLE OF INDIVIDUAL DATA TEST COMPOUND: REAKTIV-ORANGE DYPR 934 |
|||||||
Group |
Animal number |
Sex |
Dose Mg/kg body weight |
Poly/200 Ery |
Poly With MN |
Poly/Ery |
Poly With MN [%] |
1 |
1 |
male |
o-Control |
93 |
1 |
0.47 |
0.05 |
1 |
2 |
male |
o- Control |
82 |
1 |
0.41 |
0.05 |
1 |
3 |
male |
o- Control |
87 |
0 |
0.44 |
0.00 |
1 |
4 |
male |
o- Control |
117 |
3 |
0.59 |
0.15 |
1 |
5 |
male |
o- Control |
77 |
3 |
0.39 |
0.15 |
1 |
6 |
female |
o- Control |
122 |
2 |
0.81 |
0.10 |
1 |
7 |
female |
o- Control |
58 |
0 |
0.29 |
0.00 |
1 |
8 |
female |
o- Control |
83 |
4 |
0.42 |
0.20 |
1 |
9 |
female |
o- Control |
68 |
2 |
0.34 |
0.10 |
1 |
10 |
female |
o- Control |
105 |
3 |
0.53 |
0.15 |
2 |
11 |
male |
2000 |
102 |
1 |
0.51 |
0.05 |
2 |
12 |
male |
2000 |
75 |
0 |
0.38 |
0.00 |
2 |
13 |
male |
2000 |
78 |
0 |
0.39 |
0.00 |
2 |
14 |
male |
2000 |
101 |
2 |
0.51 |
0.10 |
2 |
15 |
male |
2000 |
89 |
2 |
0.49 |
0.10 |
2 |
16 |
female |
2000 |
53 |
4 |
0.32 |
0.20 |
2 |
17 |
female |
2000 |
73 |
2 |
0.37 |
0.10 |
2 |
18 |
female |
2000 |
81 |
4 |
0.41 |
0.20 |
2 |
19 |
female |
2000 |
56 |
4 |
0.28 |
0.20 |
2 |
20 |
female |
2000 |
97 |
2 |
0.49 |
0.10 |
3 |
21 |
male |
50- Endoxan® |
68 |
130 |
0.44 |
6.50 |
3 |
22 |
male |
50- Endoxan® |
75 |
110 |
0.38 |
5.50 |
3 |
23 |
male |
|
103 |
61 |
0.52 |
3.05 |
3 |
24 |
male |
50- Endoxan® |
87 |
83 |
0.44 |
4.15 |
3 |
25 |
male |
|
73 |
51 |
0.37 |
2.55 |
3 |
26 |
female |
50- Endoxan® |
67 |
73 |
0.34 |
3.65 |
3 |
27 |
female |
|
90 |
49 |
0.45 |
2.45 |
3 |
28 |
female |
50- Endoxan® |
90 |
49 |
0.38 |
3.55 |
3 |
29 |
female |
|
75 |
71 |
0.38 |
4.20 |
3 |
30 |
female |
50- Endoxan® |
75 |
42 |
0.38 |
2.10 |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
The results lead to the conclusion that REAKTIV-ORANGE DYPR 934 did not cause a substantial increase of micronucleated polychromatic erythrocytes and is not mutagenic in the micronucleus test under the conditions described in this report. - Executive summary:
A micronucleus test was carried out with Reaktiv-Orange DYPR 934. The test compound was dissolved in deionized water and was given twice at an interval of 24 hours as an orally dose of 2000 mg per body weight to approx. 7 weeks old male and female mice, based on the results of a previous dose range finding assay. According to the procedure the animals were killed after 24 hours administration.
The main purpose of the study was to assess the potential of the test compound to cause chromosomal damage (clastogenicity) in a mouse bone micronucleus test.
Endoxan ® was used as positive control substance and was administrated once orally at dose of 50 mg per kg body weight.
Endoxan ® (cyclophosphamide) induced a marked statistically significant increase in the number of polychromatic cells with micronuclei, indicating the sensitivity of the test system.
The ratio of polychromatic erythrocytes to total erythrocytes was not changed to a significant extent.
The number of polychromatic erythrocytes containing micronuclei was not increased. The ratio of polychromatic erythrocytes to total erythrocytes remained unaffected by the treatment with Reaktiv-Orange DYPR 934 and was not less 20 % on the control value.
Both biological and statistical significances were considered together for evaluation purposes.
Under the conditions of the present study the results in lead to the conclusion that REAKTIV-ORANGE DYPR 934 did not cause a substantial increase of micronucleated polychromatic erythrocytes and is not mutagenic in the micronucleus test under the conditions described in this report.
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