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EC number: 212-828-1 | CAS number: 872-50-4
- 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:
- 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- 1-methyl-2-pyrrolidone
- EC Number:
- 212-828-1
- EC Name:
- 1-methyl-2-pyrrolidone
- Cas Number:
- 872-50-4
- Molecular formula:
- C5H9NO
- IUPAC Name:
- 1-methylpyrrolidin-2-one
- Test material form:
- liquid
- Details on test material:
- - source: BASF AG
- analytical purity: purity > 99.8 %
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: BASF AG, 88/369
- Analytical purity: 99.8 %
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: +4°C to +6°C under N2 conditions
- Stability under test conditions: Stability proven by sponsor
- Solubility and stability of the test substance in the solvent/vehicle: Substance was formulated in aqua dest. immediately before administration
FORM AS APPLIED IN THE TEST
- solution
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-8741 Sulzfeld, Germany
- Weight at study initiation: not specified
- Assigned to test groups randomly: yes
- Fasting period before study: not indicated
- Housing:
during acclimation period: in Makrolon cages type III, in groups of 5 per sex
during study period: in Makrolon cages type I, individually
- Diet: ad libitum, standardized pellet (Kliba Haltungsdiät; Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland)
- Water: ad libitum
- Acclimation period: about one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully air conditioned
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle used: aqua dest.
- Justification for choice of solvent/vehicle: NMP is soluble and stable in aqua dest. for > 2 hours
- Concentration of test material in vehicle: 9.5 - 38 g/100 mL
- Amount of vehicle (if gavage or dermal): 10 mL/kg body weight - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Test groups 2 were given 3800 mg test substance/kg bw or 10 mL/kg bw of a solution with a concentration of 38 g/100 mL
Test groups 3 were given 1900 mg test substance/kg bw or 10 mL/kg bw of a solution with a concentration of 19 g/100 mL
Test groups 4 were given 950 mg test substance/kg bw or 10 mL/kg bw of a solution with a concentration of 9.5 g/100 mL - Duration of treatment / exposure:
- 24 h (950 and 1900 mg/kg bw); 16, 24 and 48 h (3,800 mg/kg bw)
24 h (solvent control and positive controls) - Frequency of treatment:
- one single test substance administration by gavage
- Post exposure period:
- not applicable
Doses / concentrationsopen allclose all
- Dose / conc.:
- 950 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 900 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 3 800 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5 animals per sex, dose and sampling interval (for NMP treatment groups and control group)
3 male and 2 female mice for cyclophosphamide treatment group
2 male and 3 female mice for vincristine treatment group - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Route of administration: gavage
- Doses / concentrations:
cyclophosphamide: 40 mg/kg bw per os (positive agent for clastogenic activity)
vincristine: 0.15 mg/kg intraperitoneal (positive agent for spindle inhibition, aneuploidy)
Examinations
- Tissues and cell types examined:
- bone marrow cells
After administration of the test substance, the animals were examined for any evident clinical signs of toxicity. - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
In a pretest for determination of the acute oral toxicity, deaths were observed down to a dose of 4640 mg/kg bw. The dose level which all animals survived was 3830 mg/kg bw, but signs of toxicity were observed at this dose level: irregular respiration and abdominal position. In addition, the general state of the animal was poor.
Therefore a dose of 3800 mg/kg bw was selected as the highest dose in this micronucleus test. 1900 mg/kg bw and 950 mg/kg bw were selected as additional dose levels.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
All test substance solutions were prepared immediately before administration. The amount of substance or volume to be administered was related to the specific weight of the individual animal on the day of the experiment. For control purposes, male and female animals were given the solvent aqua dest. by the same route.
DETAILS OF SLIDE PREPARATION:
The bone marrow was prepared according to the method described by Schmid, W. (1976 and 1977).
After cutting the epiphyses, the bone marrow ws flushed out of the diaphysis with ca. 2 mL fetal calf serum. The suspension was reduced by centrifugation and bone marrow smears were prepared onto clean microscopic slides. The slides were stained in eosin and methylene blue and after staining with Giemsa, the preparation were embedded in Entellan.
- Evaluation criteria:
- 1000 polychromatic erythrocytes from each of the male and female animals of every test group are evaluated and investigated for micronuclei. The normochromatic erythrocytes are also scored. The following parameters are recorded:
- number of polychromatic erythrocytes
- number of polychromatic erythrocytes containing micronuclei
- number of normochromatic erythrocytes
- ratio of polychromatic to normochromatic erythrocytes
- number of small micronuclei (d < D/4) and large micronuclei (d>= D/4)
d= diameter of micronuclei and D = cell diameter
- number of normochromatic erythrocytes containing micronuclei - Statistics:
- Statistical analysis: Fisher's exact test and U-test according to Mann-Whitney
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Remarks:
- Apart from irregular respiration and abdominal position that lasted from 1h to 1d, depending on the doses, there was no toxicity observed.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF DEFINITIVE STUDY
- Clinical examinations:
Doses of 3800 mg/kg bw and 1900 mg/kg bw induced irregular respiration and abdominal position immediately after test substance administration. These signs indicate the bioavailability of the test substance. 24 hours after treatment, the animals did not show clinical signs any longer.
- Induction of micronuclei (for Micronucleus assay):
No increased frequency of polychromatic erythrocytes containing either small or large micronuclei (see also table under "Any other information on results incl. tables").
- Ratio of PCE/NCE (for Micronucleus assay): Inhibition of erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected at 3800 mg/kg bw (approx. 80 % of LD50) after 24 h sacrifice only.
- Statistical evaluation:
There was no statistically significant increase in the rate of polychromatic cells with micronuclei in any animal treated with NMP
The positive controls cyclophosphamide and vincristine induced significant increases in the number of micronucleated polychromatic erythrocytes
Any other information on results incl. tables
Results at 24 h:
Dose level (mg/kg bw) |
MN/1000 PCE |
PCE examined |
NCE (found) |
0 |
22 (2.2%) |
10000 |
3423 |
NMP 950 |
16 (1.6) |
10000 |
3198 |
NMP 1900 |
22 (2.2) |
10000 |
2952 |
NMP 3800 |
21 (2.1) |
10000 |
6605 |
CPP 40 |
90 (18.0) |
5000 |
2292 |
VC 0.15 |
516 (103) |
5000 |
4132 |
MN = cells with micronuclei per 100 polychromatic erythrocytes
PCE = poylchromatic erythrocytes
NCE = normochromatic erythrocytes
CP = cyclophosphamide
VC = vincristine
Applicant's summary and conclusion
- Conclusions:
- The overall result of the in vivo micronucleus assay was a negative outcome.
- Executive summary:
NMP was tested for clastogenicity and for the ability to have spindle poison effects in the mouse micronucleus test in NMRI mice. NMP dissolved in aqua dest., was administered as a single dose orally to 5 males and 5 females/test group at dose levels of 3800, 1900 and 950 mg/kg bw in a volume of 10 mL/kg body weight. Concurrent negative control test groups (5 male and 5 female mice) were administered merely the solvent aqua.dest by the same route. As positive control for clastogenicity, 40 mg of cyclophosphamide/kg bw, dissolved in aqua dest., was administered orally to 3 male and 3 female animals. As positive control for spindel poison effects, 0.15 mg of vincristine/kg bw, dissolved in aqua dest., was administered intraperitoneally to 2 male and 2 female animals. The femora of the animals in the respective groups were prepared 16, 24 and 48 hours after test substance administration in the highest dose group of 3800 mg/kg bw. In the test groups of 1900 and 95 mg/kg bw, the negative control group and in the positive control groups, the 24 -hour interval was investigated, only. After staining of the preparations, 1000 polychromatic erythrocytes were evaluated per animal and investigated for micronuclei. The normochromatic erythrocytes were also registered. After administration of the test substance, the animals were examined for any evident clinical signs of toxicity.
Doses of 3800 mg/kg bw and 1900 mg/kg bw induced irregular respiration and abdominal position immediately after test substance administration. These signs indicate the bioavailability of the test substance. 24 hours after treatment, the animals did not show clinical signs any longer.
NMP did not increase the frequency of poylchromatic erythrocytes containing either small or large micronuclei.
The positive control substances cyclophosphamide/vincristine sulfate increased clearly the numbers of micronucleated polychromatic erythrocytes indicating the sensitivity of the test system.
These results indicate that NMP has neither a clastogenic effect nor a spindle poison effect in vivo.
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