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EC number: 203-253-7 | CAS number: 104-93-8
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to GLP and current testing guidelines.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- 4-methylanisole
- EC Number:
- 203-253-7
- EC Name:
- 4-methylanisole
- Cas Number:
- 104-93-8
- Molecular formula:
- C8H10O
- IUPAC Name:
- 1-methoxy-4-methylbenzene
- Details on test material:
- - Name of test material (as cited in study report): p-Cresolmethylether
- Physical state: liquid, colorless, clear
- Analytical purity: 98.6%
- Batch No.: 10745009T0
- Storage condition of test material: room temperature, protection from light
- Expiration Date: 2010-07-31
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories GmbH, 33178 Borchen, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: mean value 38.8 g (SD +/- 3.4 g)
- Assigned to test groups randomly: yes
- Housing: single, in Makrolon Type II/III, with wire mesh top (EHRET GmbH, 79302 Emmendingen, Germany)
- Diet: pelleted standard diet, ad libitum (Harlan Laboratories GmbH, 33178 Borchen, Germany)
- Water: ad libitum; tap water
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 45 - 65
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle used: corn oil
- Justification for choice of vehicle: The vehicle was chosen due to its relative non-toxicity for the animals.
- Concentration of test material in vehicle: 500, 1000, and 2000 mg/kg b.w.
- Amount of vehicle: 10 mL/kg bw. - Details on exposure:
- The animals received the test item, the vehicle or the positive control substance once orally
- Duration of treatment / exposure:
- 24 and 48 h
- Frequency of treatment:
- single daily administration
- Post exposure period:
- Not applicable
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
24 h preparation interval: 500, 1000 and 2000 mg/kg b.w.
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
48 h preparation interval: 2000 mg/kg b.w.
Basis:
nominal conc.
- No. of animals per sex per dose:
- 7 males in each dosing group.
5 males in the vehicle and positive control groups. - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- 40 mg/kg bw cyclophosphamide
Examinations
- Tissues and cell types examined:
- Polychromatic/Normochromatic erythrocytes (PCE) in the bone marrow
- Details of tissue and slide preparation:
- DETAILS OF SLIDE PREPARATION:
The animals were sacrificed using CO2 followed by bleeding. The femora were removed, the epiphyses were cut off and the marrow was flushed out with foetal 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 re-suspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald (Merck, 64293 Darmstadt, Germany)/Giemsa (Gurr, BDH Limited Poole, Great Britain). Cover slips were mounted with EUKITT (Kindler, 79110 Freiburg, Germany). At least one slide was made from each bone marrow sample.
Analysis of Cells
Per animal 2000 polychromatic erythrocytes (PCE) were analysed for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed in polychromatic erythrocytes per 2000 erythrocytes. The analysis was performed with coded slides. - Evaluation criteria:
- The study was considered valid as the following criteria are met:
- at least 5 animals per group can be evaluated.
- PCE to erythrocyte ratio should not be less than 20 % of the negative control.
- the positive control shows a statistically significant and biological relevant increase of micronucleated PCEs compared to the vehicle control.
Evaluation of Results
A test item is 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 are used as an aid in evaluating the results, if necessary. However, the primary point of consideration is the biological relevance of the results. A test item that fails to produce a biological relevant increase in the number of micronucleated polychromatic erythrocytes is considered non-mutagenic in this system. - Statistics:
- Nonparametric Mann-Whitney test
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
Since no gender specific differences concerning signs of toxicity in the pre-experiment were observed, the main study was performed using males only.
Clinical signs of toxicity, i.e. ruffled fur, were observed in all test substance dose groups and reduction of spontaneous activity was observed in the high dose animals.
The mean number of polychromatic erythrocytes (PCEs) was not decreased after treatment with the test item as compared to the mean value of PCEs of the vehicle control indicating that p-Cresolmethylether did not have any cytotoxic properties in the bone marrow.
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 item.
Test group | Dose (mg/kg bw) | Sampling time (h) | PCEs with micronuclei (%) | PCE per 2000 erythocytes |
Vehicle | 0 | 24 | 0.150 | 1181 |
Test item | 500 | 24 | 0.100 | 1196 |
Test item | 1000 | 24 | 0.079 | 1207 |
Test item | 2000 | 24 | 0.114 | 1141 |
Positive ctrl. | 40 | 24 | 2.840 | 1155 |
Vehicle | 0 | 48 | 0.070 | 1232 |
Test item | 2000 | 48 | 0.064 | 1030 |
Applicant's summary and conclusion
- Conclusions:
- It can be stated that under the experimental conditions reported, the test item did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse. Therefore, p-Cresolmethylether is considered to be non-mutagenic in this micronucleus assay.
- Executive summary:
The ability of p-Cresolmethylether to induce micronuclei in polychromatic erythrocytes (PCE) was investigated in the bone marrow of mice. The test item was fomulated in corn oil (vehicle control) and administered by gavage at :24 h preparation interval: 500, 1000, and 2000 mg/kg b.w and 48 h preparation interval: 2000 mg/kg b.w. Postive controls recieved 40 mg/kg bw cyclophosphamide orally. Seven males per test group (except the vehicle and positive control groups with 5 males each) were evaluated for the occurrence of micronuclei. Per animal 2000 polychromatic erythrocytes (PCEs) were scored for micronuclei. To describe a cytotoxic effect due to the treatment with the test item the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and reported as the number of PCEs per 2000 erythrocytes. The highest dose (2000 mg/kg; maximum guideline-recommended dose) was estimated by a pre-experiment to be suitable. Since no gender specific differences concerning signs of toxicity in the pre-experiment were observed, the main study was performed using males only. After treatment with the test item the number of PCEs was not substantially decreased as compared to the mean value of PCEs of the vehicle control thus indicating that pCresolmethylether did not exert any cytotoxic effects in the bone marrow. In comparison to the corresponding vehicle controls 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 item and with any dose level used. Under the experimental conditions reported, p-Cresolmethylether is considered to be non-mutagenic in this micronucleus assay.
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