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Diss Factsheets
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EC number: 457-320-2 | 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 26 May to 2 June 1998
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study (with certain deviations), to GLP, on related material
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- only one sampling time, a second sampling time is recommended where two or more daily doses are given
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Details on test material:
- - Name of test material (as cited in study report): MRD-98-158
- Substance type: technical product
- Physical state: black liquid
- Analytical purity: no data
- Expiration date of the lot/batch: February 2003
- Stability under test conditions: stable for at least 8 days in peanut oil
- Storage condition of test material: room temperature
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: about 9 weeks
- Weight at study initiation: males: 30.1-35.3 g; females: 22.6-28.3 g
- Assigned to test groups randomly: yes, using computer-generated body weight sorting programme
- Fasting period before study: no data
- Housing: singly in suspended stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Peanut oil
- Vehicle(s)/solvent(s) used: peanut oil
- Justification for choice of solvent/vehicle: test substance soluble in peanut oil
- Concentration of test material in vehicle: 50, 100 and 200 mg/ml
- Amount of vehicle (if gavage or dermal): 10.0 ml/kg bw
- Lot/batch no. (if required): 116H1037
- Purity: no data - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: dosing solutions prepared once and used for all 3 days of dosing
- Duration of treatment / exposure:
- 3 days
- Frequency of treatment:
- daily for 3 days
- Post exposure period:
- 18-24 hr after the last dose
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 500, 1000 or 2000 mg/kg bw/day
Basis:
actual ingested
nominal dose
- Remarks:
- Doses / Concentrations:
0, 472, 939 or 1640-1930 mg/kg bw/day
Basis:
actual ingested
analytical dose
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Positive control substance: cyclophosphamide
- Justification for choice of positive control(s): included in list of recommended substances
- Route of administration: oral gavage
- Doses / concentrations: 20 mg/kg bw/day
Examinations
- Tissues and cell types examined:
- bone marrow erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: based on range-finding study
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): treated daily for 3 days with 0, 500, 1000 or 2000 mg/kg bw/day. Samples taken 18-24 hr after the last dose.
DETAILS OF SLIDE PREPARATION: bone marrow aspirated from the femurs, washed, centrifuged and the erythrocytes resuspended in any remaining supernatent. Bone marrow smears were prepared (2/animal) and the slides stained with acridine orange.
METHOD OF ANALYSIS: 2000 polychromatic erythrocytes (PCEs) per animal were examined for the presence of micronuclei. The percentage of PCEs were determined by counting 1000 erthrocytes per animal. - Evaluation criteria:
- The test substance was considered positive if the mean incidence of micronucleated PCEs showed a dose-related increase, including at least one dose that was statistically different from the mean incidence in the vehicle control groups and outside the normal mean range of the vehicle controls (ie. greater than 4), or at least two dose levels are statistically different from the normal range for the vehicle control (again, greater than 4).
- Statistics:
- Standard one-way analysis of variance (ANOVA) and, if this was significant, Duncan's multiple range test was used to compare vehicle and treated groups. A standard regression analysis was performed to test for dose-response.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Doses producing toxicity: Evidence of cytotoxicity was observed at 1000 mg/kg bw/day (males and females) and 2000 mg/kg bw/day (males only) as indicated by a significant decrease in PCE/NCE ratio compared with controls.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 0, 500, 1000 or 2000 mg/kg bw/day
- Solubility: yes
- Clinical signs of toxicity in test animals: none observed, and body weights did not change during the study.
- Evidence of cytotoxicity in tissue analyzed: none observed
- Rationale for exposure: no data
- Harvest times: 18-24 hr after the last dose
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no induction in the treated groups
- Ratio of PCE/NCE (for Micronucleus assay): see Table 1 (below)
- Statistical evaluation: not applicable, no induction of micronuclei
Any other information on results incl. tables
Table 1. Mean number of micronuclei and PCE:NCE ratios per treatment
Males (mean of 5 animals) | Females (mean of 5 animals) | |||
%PCE (ratio PCE:NCE) | Micronuclei/100PCEs | %PCE(ratio PCE:NCE) | Micronuclei/100PCEs | |
0 mg/kg bw/day (vehicle control) | 54.46 ± 3.34 (1.18) | 0.8 ± 0.8 | 53.14 ± 1.63 (1.13) | 1.2 ± 0.7 |
500 mg/kg bw/day | 49.68 ± 4.28 (0.99) | 1.2 ± 0.4 | 51.32 ± 4.41 (1.05) | 0.4 ± 0.2 |
1000 mg/kg bw/day | 47.88 ± 5.64** (0.92) | 0.4 ± 0.2 | 45.64 ± 5.56* (0.84) | 0.7 ± 0.8 |
2000 mg/kg bw/day | 44.54 ± 2.87** (0.80) | 1.3 ± 0.6 | 47.40 ± 5.11 (0.90) | 1.4 ± 0.7 |
20 mg/kg bw/day cyclophosphamide | 36.78 ± 3.90** (0.58) | 9.9 ± 2.2** | 36.66 ± 6.65** (0.60) | 11.3 ± 1.6** |
* p < 0.05; ** p < 0.01
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
In a GLP study conducted according to OECD guideline 474, test substance MRD-98-158 (EC#434-650-5) showed no genotoxic potential in an in vivo bone marrow micronucleus assay when given orally to male and female mice at doses of up to 2000 mg/kg bw/day for three consecutive days. - Executive summary:
In a GLP study conducted according to OECD guideline 474, the genotoxic potential of test substance MRD-98-158 (EC# 434-650-5) was assessed in an in vivo bone marrow micronucleus assay in mice.
Groups of five CD-1 mice of each sex were dosed via gavage with 0, 500, 1000 or 2000 mg/kg bw/day for three consecutive days with the test substance in peanut oil. Between 18-24 hr after the final dose, bone marrow erythrocytes were recovered from the femurs of the animals and used to prepare two slides per animal for examination. After staining with acridine orange, 2000 polychromatic erythrocytes per animal were scored for the presence of micronuclei. To detemine cytotoxicity the number of polychromatic erythrocytes in the total erythrocyte population were counted.
No increase in micronucleated cells was evident in the treated groups compared to the vehicle controls. Cytotoxicity, indicated by a reduction in the ratio of polychromatic erythrocytes to normochromatic erythrocytes, was detected at the mid- and high-dose levels in males and the mid-dose in females.The positive controls gave the expected increase in micronuclei demonstrating the effective performance of the assay.
In conclusion, EC# 434-650-5 showed no genotoxic potential in an in vivo bone marrow micronucleus assay when given orally to male and female mice at doses of up to 2000 mg/kg bw/day for three consecutive days.
In view of the structural and chemical similarities, it is considered that the results of this study can be used for read-across to EC# 457-320-2.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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