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EC number: 604-351-6 | CAS number: 143390-89-0
- 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 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:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- mouse
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- methyl (2E)-2-methoxyimino-2-[2-[(2-methylphenoxy)methyl]phenyl]acetate
- EC Number:
- 604-351-6
- Cas Number:
- 143390-89-0
- Molecular formula:
- C18 H19 N O4
- IUPAC Name:
- methyl (2E)-2-methoxyimino-2-[2-[(2-methylphenoxy)methyl]phenyl]acetate
- Details on test material:
- - Name of test material (as cited in study report): Reg. No. 242 009 (test substance number: 91/180-2)
- Lot/batch No.: N 36 (III c 1); date of manufaturing: 1991-10-23
- Storage condition of test material: approx. Refrigerator (protected from light)
- Physical state: lightbrown powder
- Analytical purity: 94.3% (Reversed-Phase - HPLC with UV-Detection analysed 1993-04-26/27)
- Stability under test conditions: the storage stability was guaranteed over the study period (stability in DMSO/water: stable for at least 4 hours)
- Other: the homogeneity of the test substance was confirmed by analysis (Reversed-Phase - HPLC with UV-Detection)
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 GmbH, WIGA, D-W8741 Sulzfeld, FRG
- Age at study initiation: healthy young adult animals
- Weight at study initiation: mean weight of 28 g
- Assigned to test groups randomly: yes
- Fasting period before study: ot reported
- Housing: before the start of the treatment the animals were transferred to Makrolon cages, type M I, and housed individually under the same conditions until the end of the test.
- Diet (e.g. ad libitum): Standardized pelleted feed (Kliba Haltungsdiat, Klingentalmuhle AG, CH-4303 Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): drinking water
- Acclimation period: for the duration of about one week the animals were housed in groups of 5 separately according to sex in fully air-conditioned rooms in which central air conditioning.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose); 0.5% CMC formulation
- Justification for choice of solvent/vehicle: suspension with a concentration of 20 g/100 ml (2000 mg/kg dose group), 10 g/100 ml (1000 mg/kg dose group) and 5 g/100 ml (500 mg/kg dose group)
- Concentration of test material in vehicle: the test substance to be administered per kg body weight was suspended in an 0.5% CMC formulation.
- Amount of vehicle (if gavage or dermal): 10 ml/kg - Details on exposure:
- IP application: first test group were given 2000 mg/kg bw (10 ml/kg bw of a suspension at 20 g/100 ml; second test group 1000 mg/kg bw (10 ml/kg bw of suspension at 10 g/100 ml); and third test group 500 mg mg/kg bw (10 ml/kg bw of suspension at 5 g/100 ml)
- Duration of treatment / exposure:
- once
- Frequency of treatment:
- once
- Post exposure period:
- 16, 24 or 48 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500, 1000 and 2000 mg/kg bw
Basis:
analytical conc.
actually injected
- No. of animals per sex per dose:
- 5 the negative control and test substance group and 2/3 in the positive control group (Table 1)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- none; no data; 20 mg cyclophosphamide (10 ml test solution); 0.15 mg vincristine (10 ml test solution)
- Route of administration: IP
- Doses / concentrations: the control animals were sacrificed 24 hours after administration of the solvent. The control animals were treated at different times so that it was always possible to prepare control animals simultaneously for all the different sacrifice intervals of the test animals.
Examinations
- Tissues and cell types examined:
- femoral bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
In a pretest for the determination of the acute intraperitoneal toxicity the amount of 2000 mg/kg body weight recommended as the highest dose according to the EEC Directive 84/449, B 12., was survived by all animals but led to clinical signs of toxicity (see below). Therefore, a dose of 2000 mg/kg body weight was selected as the highest dose in the present cytogenetic study. 1000 mg/kg and 500 mg/kg body weight were administered as further doses.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
See Table 1
DETAILS OF SLIDE PREPARATION:
- The two femora were prepared from the animals, and all soft tissues were removed.
- After cutting off the epiphyses, the bone marrow was flushed out of the diaphysis into a centrifuge tube using a cannula filled with fetal calf serum which was at 37 0C (about 2 ml/femur).
- The suspension was mixed thoroughly with a pipette, centrifuged at 1500 rpm for 5 minutes, the supernatant was removed except for a few drops, and the precipitate was resuspended.
- 1 drop of this suspension was dropped onto clean microscopic slides, using a Pasteur pipette. Smears were prepared using slides with ground edges, the preparations were dried in the air and subsequently stained.
- Staining: The slides were stained in eosin and methylene blue solution for 5 minutes, rinsed in aqua dest. and then placed in fresh aqua dest. for 2 or 3 minutes. They were finally stained in Giemsa solution for 12 minutes. After being rinsed twice in aqua dest. and clarified in xylene, the preparations were embedded in Corbit-Balsam.
METHOD OF ANALYSIS:
In general, 1000 polychromatic erythrocytes from each of the male and female animals of every test group are evaluated and investigated for micronuclei. The normochromatic erythrocytes (= normocytes), which occur, are also scored. The following parameters are recorded: (1) Number of polychromatic erythrocytes. (2) Number of polychromatic erythrocytes containing micronuclei. The increase in the number of micronuclei in polychromatic erythrocytes of treated animals as compared with the solvent control group provides an index of a chromosome-breaking (clastogenic) effect or of a spindle activity of the substance tested. (3) Number of normochromatic erythrocytes. (4) Number of normochromatic erythrocytes containing micronuclei. The number of micronuclei in normochromatic erythrocytes at the early sacrifice intervals represents the situation before test substance administration and may serve as a control value. A substance-induced increase in the number of micronuclei in normocytes may be found with an increase in the duration of the sacrifice intervals. (5) Ratio of polychromatic to normochromatic erythrocytes. This ratio indicates an influence of the test substance specifically on the bone marrow. (6) Number of small micronuclei (d < D/4) and of large micronuclei (d ≥ D/4) (d = diameter of micronucleus, D = cell diameter) The size of micronuclei may give an indication on the possible mode of action of the test substance, i.e. a clastogenic or a spindle poison effect.
Slides were coded before microscopic analysis
OTHER:
- Clinical examinations
After the administration of the test substance the animals were examined for any evident clinical signs of toxicity. - Evaluation criteria:
- The mouse micronucleus test is to be considered valid if the following criteria are met: (1) the quality of the slides allowed the identification and evaluation of a sufficient number of analyzable cells, i.e. ≥ 1000 polychromatic erythrocytes; (2) the positive control chemical induced a significant increase in the number of cells containing micronuclei. The test chemical is to be considered positive in this assay if the following criteria are met: (1) a dose-related and significant increase in the number of micronucleated polychromatic erythrocytes at any of the intervals. (2) The proportion of cells containing micronuclei exceeded the values of the concurrent negative control range. A test substance is generally considered negative in this test system if: (1) there was no significant increase in the number of micronucleated polychromatic erythrocytes at any dose above concurrent control frequencies and at any time.
- Statistics:
- A statistical evaluation was not necessary to perform. The number of polychromatic micronucleated erythrocytes after test substance treatment was nearly the range of the actual control value and within the historical values.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Remarks:
- see below (and Table 2)
- Toxicity:
- yes
- Remarks:
- See below: Clinical signs
- Vehicle controls validity:
- valid
- Negative controls validity:
- other: results are within the range of the historic controls from the same testing facility
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 2000 mg/kg bw
- Solubility: administered as suspension in 0.5% CMC
- Clinical signs of toxicity in test animals: signs of toxicity such as irregular respiration, piloerection, squatting posture, apathy, poor general state and closed eyelids within 5 hours after treatment were observed
RESULTS OF DEFINITIVE STUDY
The single intraperitoneal administration of a 0.5% CMC formulation in a volume of 10 ml/kg body weight led to 2.3% polychromatic erythrocytes containing micronuclei after the 24-hour sacrifice interval.
After the single administration of the highest dose of 2000 mg/kg body weight, 2.8% polychromatic erythrocytes containing micronuclei were found after 16 hours, 2.2% after 24 hours and 2.0% after 48 hours.
In the two lower dose groups rates of micronuclei of about 2.0% (1000 mg/kg group) and 1.9% (500 mg/kg group) were detected after a sacrifice interval of 24 hours in each case.
With 25.6% the positive control substance cyclophosphamide for clastogenicity led to the expected increase in the number of polychromatic erythrocytes containing mainly small micronuclei at a dose level of 20 mg/kg body weight.
With 97.8% the positive control vincristine for spindle poison effects also led to a clearly enhanced number of micronuclei containing polychromatic erythrocytes with the expected amount of large micronuclei, i.e. 15.0%.
The number of normochromatic erythrocytes containing micronuclei did not differ to any appreciable extent in the negative control or in the various dose groups at any of the sacrifice intervals.
Thus, the test substance Reg. No. 242 009 did not lead to any increase in the rate of micronuclei. The number of normochromatic or polychromatic erythrocytes containing small micronuclei (d < D/4) or large micronuclei (d ≥ D/4) did not deviate from the solvent control value at any of the sacrifice intervals.
No inhibition of erythropoiesis induced by the treatment of mice with Reg. No. 242 009 was detected; the ratio of polychromatic to normochromatic erythrocytes was always in the same range as that of the control values in all dose groups.
Any other information on results incl. tables
Clinical signs:
The single intraperitoneal administration of the carrier in a volume of 10 m1/kg body weight was tolerated by all animals without any signs or symptoms.
A single intraperitoneal dose of 2000 mg/kg body weight led to irregular respiration, pi1oerection and in few cases, to squatting posture, apathy and closed eyelids about 30 minutes after administration; the general state of the animals was poor. Some of these signs were observed for about 4 hours after treatment.
About 30 minutes after treatment of the animals with doses of 1000 mg/kg or 500 mg/kg irregular respiration, pi1oerection and squatting posture were observed which lasted for about 30 minutes.
Neither the single administration of the positive control substance cyclophosphamide in a dose of 20 mg/kg body weight nor that of vincristine in a dose of 0.15 mg/kg body weight caused any evident signs of toxicity.
Table 2: Analysis of the polychromatic and monochromatic erythrocytes (mean values)
Treatment group |
Dosis |
Sacrifice interval |
Polychromatic erythrocytes in a total of 1000 cells examined |
Normochromatic erythrocytes |
||||
Cells with MN d<¼ D |
Cells with MN d≥¼ D |
Total micronucleus |
Total number of cells |
Cells with MN |
||||
Number |
% |
|||||||
Vehicle control |
0 |
24 |
2.3 |
0 |
2.3 |
2.3 |
445.0 |
1.4 |
Test substance |
2000 |
16 |
2.6 |
0.2 |
2.8 |
2.8 |
479.3 |
0.8 |
2000 |
24 |
2.1 |
0.1 |
2.2 |
2.2 |
485.2 |
1.2 |
|
2000 |
48 |
1.8 |
0.2 |
2.0 |
2.0 |
485.0 |
0.8 |
|
1000 |
24 |
1.9 |
0.1 |
2.0 |
2.0 |
485.1 |
0.6 |
|
500 |
24 |
1.9 |
0 |
1.9 |
1.9 |
501.6 |
1.1 |
|
Cyclophosphamide |
20 |
24 |
25.4 |
0.2 |
25.6 |
25.6 |
446.0 |
0.6 |
Vincristine |
0.15 |
24 |
82.8 |
15 |
97.8 |
97.8 |
576.2 |
2.2 |
MN: Micronucleus; d: diameter of the micronucleus; D: diameter of the cell |
Applicant's summary and conclusion
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.
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