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EC number: 939-180-9 | 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:
- 6 June to 12 July 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Performed according to OECD test guidelines and GLP principles.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- 2-({3-[2,2-bis({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butoxy]-3-oxopropoxy}methyl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butyl 3-(2-methylaziridin-1-yl)propanoate; 2-ethyl-6-(2-methylaziridin-1-yl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)-4-oxohexyl 3-(2-methylaziridin-1-yl)propanoate
- EC Number:
- 939-180-9
- Molecular formula:
- Not relevant - Multiconstituent substance
- IUPAC Name:
- 2-({3-[2,2-bis({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butoxy]-3-oxopropoxy}methyl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butyl 3-(2-methylaziridin-1-yl)propanoate; 2-ethyl-6-(2-methylaziridin-1-yl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)-4-oxohexyl 3-(2-methylaziridin-1-yl)propanoate
- Details on test material:
- - Name of test material (as cited in study report): Standard CX-100
- Physical state: clear colourless sllightly viscous liquid
- Batch: 310F-0699
- Purity: 99%
- Expiration date of the lot/batch: 30 January 2012
- Storage condition of test material: At room temperature in the dark
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: males 34-39 g, females 25-29 g
- Assigned to test groups randomly: yes
- Fasting period before study: not reported
- Housing: 5 animals/cage in polycarbonate cages, contining sterilised sawdust as bedding material.
- Diet (ad libitum): Pelleted rodent diet (SM F/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-22.1
- Humidity (%): 41-75
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: physiological saline
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: test substance was suspended in physiological saline. These were dosed within approx 2 hours after preparation.
- Duration of treatment / exposure:
- not applicable
- Frequency of treatment:
- once
- Post exposure period:
- 24 or 48 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
25, 50, 100 mg/kg bw
Basis:
other: injected
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide
- Justification for choice of positive control(s):
- Route of administration: ip
- Doses / concentrations: 40 mg/kg bw
Examinations
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: An intraperitoneal injection of a maximum tolerated, an intermediate and a low dose of substance was given to the mice. The route of administration was chosen to maximise the chance of the substance reaching the target tissue. First a dose range finding study was done.
TREATMENT AND SAMPLING TIMES: Three dose levels were used at the first sampling time. At the second sampling time only the highest dose was used. First sampling time was 24 h after treatment and second sampling time was 48 after treatment.
DETAILS OF SLIDE PREPARATION: Bone marrow suspension was placed on a slide, which was air dried, fixed for 5 min in 100% methanol and air dried overnight. Two slides/animal were prepared. They were stained, based on Giemsa.
METHOD OF ANALYSIS: All slides were randomly coded before examination. The number of micronucleated polychromatic erythrocytes was counted in 2000 polychromatic erythrocytes. The ratio of polychromatic to normochromatic erythrocytes was determined by counting and differentiating the first 1000 erythrocytes at the same time. Micronuclei were only counted in polychromatic erythrocytes. Averages and standard deviations were calculated.
OTHER: - Evaluation criteria:
- A micronucleus test is considered acceptable if it meets the following criteria:
a) The incidence of micronucleated polychromatic erythrocytes in the positive control animals should be above the historical control data range.
b) The positive control substance induced a statistically significant (Wilcoxon Rank Sum Test, one-sided, p < 0.05) increase in the frequency of micronucleated polychromatic erythrocytes.
c) The incidence of micronucleated polychromatic erythrocytes in the control animals should reasonably be within the laboratory historical control data range.
Equivocal results should be clarified by further testing using modification of experimental conditions.
A test substance is considered positive in the micronucleus test if:
- it induced a biologically as well as a statistically significant increase in the frequency of micronucleated polychromatic erythrocytes (at any dose or at any sampling time) in the combined data for both sexes or in the data for male or female groups separately and the number of micronucleated polychromatic erythrocytes in the animals are above the historical control data range.
A test substance is considered negative in the micronucleus test if:
- none of the tested concentrations or sampling times showed a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes either in the combined data for both sexes or in the data for male or female groups separately and the number of micronucleated polychromatic erythrocytes in the animals are within the historical control data range. - Statistics:
- Statistical significance was determined with the Wilcoxon Rank Sum Test, one-sided, p < 0.05.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- at 100 mg/kg bw, male animals which were sampled at 48 hours, showed a minor decrease in the ratio of polychromatic to normochromatic erythrocytes
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 100 mg/kg bw in one male and one female
- Clinical signs of toxicity in test animals: Within one hour after dosing the animals showed the following toxic signs: hunched posture and rough coat (female). Within 4 hours after dosing the male animal had a rough coat, hunched posture and closed eyes. The female animal remained its hunched posture. After 20 and 44 hours male animals were lethargic, had a hunched posture, a rough coat and closed eyes. The female animals had a hunched posture and a rough coat.
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no
- Ratio of PCE/NCE (for Micronucleus assay): minor decrease after 48 hrs
- Appropriateness of dose levels and route: ip route of exposure maximises the chance of the test substance reaching the target tissue. Minimal toxicity was observed by a decrease in PCE/NCE and some clinical signs at the highest dose only.
- Statistical evaluation: Student's t'test, p<0.02
Any other information on results incl. tables
Main test:
In the 100 mg/kg bw group: During the first two hours after dosing all animals had a hunched posture. Four males and two females also had a rough coat. Within 19 hours after dosing all animals still had a hunched posture. All males and two female animals also had a rough coat. After 43 hours the animals had a hunched posture. One male animal also had a rough coat.
In the 50 and 25 mg/kg bw group no clinical signs of toxicity or mortality was observed.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
CX100 showed no evidence of a mutagenic potential, when administered intraperitoneally to mice, in the in vivo micronucleus test. - Executive summary:
An additional study was performed in 2011, according to OECD474. This study was performed because in time the production process of the substance has changed significantly and in addition due to the unknown genetic toxicity status of the substance more information was required for CLP classification and REACH registration (which molecular weight substance would be preferable).
Mice were dosed intraperitoneally once (25, 50 and 100 mg/kg bw). At 100 mg/kg bw no evidence of a mutagenic potential was shown, toxicity was shown by some clinical signs (hunched posture, rough coat, closed eyes), while a decrease in the ratio of polychromatic to normochromatic erythrocytes confirmed exposure of the target tissue.
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