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EC number: 258-420-7 | CAS number: 53185-52-7
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06 September 2011 - 13 October 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
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)
- Version / remarks:
- 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 30 May 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
- Version / remarks:
- August 1998
- Deviations:
- no
- Principles of method if other than guideline:
- ICH Guidance S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals, 1996.
ICH Guidance S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals, 1997. - GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Test material
- Reference substance name:
- 3-methoxy-N,N-dimethylpropionamide
- EC Number:
- 258-420-7
- EC Name:
- 3-methoxy-N,N-dimethylpropionamide
- Cas Number:
- 53185-52-7
- Molecular formula:
- C6H13NO2
- IUPAC Name:
- 3-methoxy-N,N-dimethylpropanamide
- Test material form:
- liquid
- Details on test material:
- - Appearance: Clear colourless liquid
- Storage condition of test material: Room temperature (15-25°C)
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: RjHan: NMRI
- Details on species / strain selection:
- The NMRI mouse is one of the standard animals used internationally in this type of mutagenicity testing.
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Elevage Janvier, Route des Chènes Secs B.P. 4105, 53940 LE GENEST-ST-ISLE, France
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: 34.4 - 36.6g
- Assigned to test groups randomly: yes, based on body weights.
- Fasting period before study: no data
- Housing: Group caging of 5 animals/ cage (type II. polypropylene/polycarbonate cage).
- Diet: free access to Autoclavable Complete Feed for mice and rats - breeding and maintenance (SM R/M-Z+H from SNIFF Spezialdiäten GmbH, D-59494 Soest, Germany)
- Water: free access to tap water from the municipal supply
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS (set to maintain, maintest)
- Temperature (°C): 20.1 - 22.8
- Humidity (%): 48 - 61
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle: physiol. saline
- Justification for choice of vehicle: Based on the result of a preliminary solubility test, the test item was dissolved in physiological saline.
- Concentration of test material in vehicle: 50, 100 and 200 mg/mL - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The necessary amount of the test item was weighed into a calibrated volumetric flask; the appropriate amount of vehicle was added and stirred to obtain homogenous formulations.
The concentration of the test item formulation was chosen to assure the same dosing volumes in mice for all dose levels (10 mL/kg bw).
The formulations were prepared just before the treatment.
- Duration of treatment / exposure:
- 24 and 48 hours
- Frequency of treatment:
- Single treatment.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- Dose / conc.:
- 2 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 5 males
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide
- Justification for choice of positive control: no data
- Route of administration: intraperitoneal injection
- Doses / concentrations: 60 mg/kg bw / 6.0 mg/mL (dissolved in sterile physiological saline)
Examinations
- Tissues and cell types examined:
- Two thousand polychromatic erythrocytes (PCEs) were scored per animal to assess the incidence of the micronucleated cells.
The proportion of immature among total (immature +mature) erythrocytes was be determined for each animal by counting a total of at least 1000 cells (immature + erythrocytes, PCEs plus mature normochromatic erythrocytes, NCEs), in which the number of micronuclei were recorded in both types of erythrocytes. - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Based on the results of the preliminary toxicity test, 2000 mg/kg body weight (the maximum recommended dose) was selected for the highest dose level of the test item in the main micronucleus test. Two lower dose levels separated by a factor of two (1000 and 500 mg/kg body weight) were also included in the main test.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
In the low and mid dose groups, furthermore in the positive control group the sampling was made once at 24 hours after treatment. In the high dose group and vehicle control group, sampling was made 24 and 48 hours after treatment. Five male animals per dose group were used for sampling on each one occasion.
DETAILS OF SLIDE PREPARATION:
The bone marrow was flushed out of each pair of femurs with foetal bovine serum (5 mL) using a syringe and needle into a sterile centrifuge tube. After mixing, the cell suspension was concentrated by a gentle centrifugation and the supernatant was discarded. Smears of the cell pellet were made on standard microscope slides (2 slides / animal). Slides were air-dried at room temperature for approximately 24 hours.
Dried slides were fixed in methanol for a minimum of 5 minutes and allowed to air-dry. Two slides per animal were stained with 10 % Giemsa solution for 20 minutes then thoroughly rinsed with distilled water, and then air-dried at room temperature for at least 12 hours. After staining, coverslips were mounted on them.
METHOD OF ANALYSIS:
Microscope analysis.
Two thousand polychromatic erythrocytes (PCEs) were scored per animal to assess the incidence of the micronucleated cells. The frequency of micronucleated cells was expressed as percent of micronucleated cells based on the first 2000 PCEs counted in the optic field. Fewer than 2000 PCEs may be counted in the event of a clear positive effect.
The proportion of immature among total (immature +mature) erythrocytes was be determined for each animal by counting a total of at least 1000 cells (immature + erythrocytes, PCEs plus mature normochromatic erythrocytes, NCEs), in which the number of micronuclei were recorded in both types of erythrocytes. - Evaluation criteria:
- Criteria for a positive response:
The test item is considered to have shown genotoxic activity if statistically significant increases in the frequency of micronucleated polychromatic erythrocytes are observed in treated animals compared to the corresponding negative controls, and the increases are dose-related. Historical control data are taken into consideration when evaluating the biological significance of small increases.
Criteria for a negative response:
The test item is concluded to have given a negative response if no reproducible, statistically significant increases are observed above the concurrent and historical control values.
Equivocal response:
Results which do not meet the criteria for a positive or negative response are considered to be equivocal. Further investigations or scoring of additional cells may be necessary in case of an equivocal result. - Statistics:
- Kruskal-Wallis test.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 2000, 1000, 500 and 250 mg/kg body weight (2 animals/sex/group; 35.6 - 37.4g: males; 28.7 - 30.6g: females).
- Solubility: the test item was soluble in physiological saline at 200 mg/mL concentration.
- Clinical signs of toxicity in test animals: In the highest dose group (2000 mg/kg body weight) piloerection and hunched back were observed for one male animal on the first day; other male animals and all the female animals were free of clinical signs on this day. All animals were free of clinical signs 24 and 48 hours after the treatment.
Based on the results of the preliminary toxicity test, dose levels of 2000, 1000 and 500 mg/kg body weight were selected for the micronucleus test. As there were no differences between male and female animals in the preliminary experiment, the main experiment was performed using male mice only.
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): No indication of an increase in the number of micronucleated normochromatic erythrocytes was observed in the study.
- Ratio of PCE/NCE (for Micronucleus assay): The ratio in the treated animals was comparable to the ratio in the negative control group at all dose levels.
- Clinical signs of toxicity in test animals:
No mortality or signs of systemic toxicity were observed during the study. In the high dose group (2000 mg/kg body weight), hunched back and/or piloerection was observed for one or more animals on the first day. The animals in the mid and low dose groups, furthermore in the negative (vehicle) control and positive control groups were symptom-free during the whole observation period.
No marked effect of test item treatment on the body weight of the mice was observed in the main test.
- Statistical evaluation:
The average number of micronuclei in the treated animals at 24h was less than the negative control group at all dose levels, therefore statistical analysis was not necessary. Comparison of the vehicle control data and the high dose of the test agent (2000 mg/kg bw) at 48h using the Kruskal-Wallis test gave a value of H = 1.3816. This is non-significant, giving a negative response.
The positive and negative control results were also compared, and gave a value of H = 6.991 (p<0.01). The positive control treatment therefore caused a large, statistically significant increase, demonstrating the sensitivity of the test system.
The frequency of micronucleated polychromatic erythrocytes of the negative (solvent) control group was within the range of historical laboratory control data; the positive control item produced a biologically and statistically relevant increase in the number of micronucleated polychromatic erythrocytes.
Applicant's summary and conclusion
- Conclusions:
- A Mammalian Erythrocyte Micronucleus Test in male mice with 3-methoxy-N,N-dimethylpropanamide was performed according to OECD 474 guideline and GLP principles.
It is concluded that 3-methoxy-N,N-dimethylpropanamide is not genotoxic. - Executive summary:
In a Mammalian Erythrocyte Micronucleus Test, male mice were exposed to different concentrations of 3-methoxy-N,N-dimethylpropanamide (dissolved in physiological saline), according to OECD 474 guideline and GLP principles.
Based on the results of the preliminary toxicity test, 2000 mg/kg body weight (the maximum recommended dose) was selected for the highest dose level of the test item in the main micronucleus test. Two lower dose levels separated by a factor of two (1000 and 500 mg/kg body weight) were also included in the main test. In the low and mid dose groups, furthermore in the positive control group the sampling was made once at 24 hours after treatment. In the high dose group and vehicle control group, sampling was made 24 and 48 hours after treatment. Five male animals per dose group were used for sampling on each one occasion. Reliable negative and positive controls were included,. No mortality or signs of systemic toxicity were observed during the study. In the high dose group (2000 mg/kg body weight), hunched back and/or piloerection was observed for one or more animals on the first day. The animals in the mid and low dose groups, furthermore in the negative (vehicle) control and positive control groups were symptom-free during the whole observation period. No marked effect of test item treatment on the body weight of the mice was observed in the main test.
No indication of an increase in the number of micronucleated normochromatic erythrocytes was observed in the study.
Based on the results, it is concluded that 3-methoxy-N,N-dimethylpropanamide is not genotoxic in the Mammalian Erythrocyte Micronucleus Test.
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