Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 258-061-6 | CAS number: 52636-67-6
- 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 germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable publication which meets basic scientific principles; limited information on test animals. Study with a structur analogous substance. For readacross justification please refer to IUCLID section 13.
Data source
Reference
- Reference Type:
- publication
- Title:
- Transplacental mutagenesis of products formed in the stomach of golden hamsters given sodium nitrite and morpholine.
- Author:
- Inui N, Nishi Y, Taketomi M, Mori M, Yamamoto M, Yamada T & Tanimura A
- Year:
- 1 979
- Bibliographic source:
- Int. J. Cancer 24: 365-372.
Materials and methods
- Principles of method if other than guideline:
- Hamster embryos were exposed in utero to the action of sodium nitrite and Morpholine or Morpholine alone administered by stomach tube to the mothers on the 11th or 12th day of pregnancy. Embryo cells were examined for chromosomal aberrations, micronucleus formation, morphological or malignant transformation and drug resistance mutations. For detection of induced mutations, the embryo cells were cultured in normal medium for 72 h and then transferred to medium containing 10 or 20 µg/mL of 8-azaguanine or 1 mM ouabain.
- GLP compliance:
- not specified
- Type of assay:
- other: choromosome aberration assay and micronucleus test
Test material
- Reference substance name:
- Morpholine
- EC Number:
- 203-815-1
- EC Name:
- Morpholine
- Cas Number:
- 110-91-8
- Molecular formula:
- C4H9NO
- IUPAC Name:
- morpholine
- Test material form:
- other: solid
- Details on test material:
- - Name of test material: Morpholine
- Supplier: Wako Chemical Industries Ltd., Tokyo, Japan
Constituent 1
Test animals
- Species:
- hamster
- Strain:
- other: Syrian golden hamster
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 150 ± 30 g
- Age at study initiation: young adult (based on body weight)
- Housing: closed colony in a clean barrier system room
- Diet: sterilized standard laboratory chow (Japan Clea Ltd., Tokyo, Japan), ad libitum
- Water: ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle used: water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Morpholine was dissolved at a concentration of 500 mg/mL in distilled water immediately before use. - Duration of treatment / exposure:
- single treatment on the 11th or 12th day of pregnancy
- Frequency of treatment:
- once
- Post exposure period:
- Twenty-four hours after treatment, hamster embryos were excised.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- no numbers given; all foetuses from each litter were used
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- N-nitrosomorpholine (Dr. Okada, Tokyo Biochemical Institute, Tokyo, Japan)
- Justification for choice of positive control: active compound
- Route of administration: oral gavage
- Doses / concentrations: 100 or 200 mg/kg bw; 500 mg/mL
Examinations
- Tissues and cell types examined:
- Primary cultures of trypsinized cells
- Details of tissue and slide preparation:
- DETAILS OF SLIDE PREPARATION:
Preparation of samples for examination of chromosomes and micronucleus formation:
For preparation of chromosomes, some cells were treated with 0.3 µg/mL of colcemid for 3 h, within 24 h of initiation of the primary culture, so that mitotic cells could then be studied in the first cell cycle in culture. Chromosome preparations were made by the usual air-dry method with a slight modification (Rothfels & Simonovitch, 1958; Yoshida et al., 1970) and stained with Giemsa. The numbers and types of chromosomal aberrations were assessed by 200 well-spread metaphase plates. For examination of micronucleus formation, samples were made by a modification of the method of Schmid (1975); 36 h after initiation of cell cultures, the cells were collected with 0.1 % trypsin, smeared on glass slides and fixed with methanol for 30 min. The slides were dried and stained with Giemsa. Per experiment, over 5000 resting nuclei were examined for micronucleus formation.
Selection of resistant mutant cells:
For selection of drug-resistant mutant cells, standard-incubated primary cultures were inoculated into medium containing 10 or 20 µg/mL of 8-azaguanine (8AG) or 1 mM ouabain (Oua) in 60 mm plastic dishes. At least five independent experiments were made. For selection of 8AG-resistant mutations, the medium containing 8AG was changed every day for the first 3 days and then, when cells that could not produce colonies had died, the medium was changed once every 3 days. For selection of Oua-resistant mutants, the medium containing 1 mM Oua was changed after 1 week. After total cultivation periods of 15 to 20 days (8AG) and 30 days (Oua), dishes were fixed and stained, and the number of resistant colonies was investigated. Embryonic cells were obtained from mothers treated with Morpholine; embryonic cells from untreated mothers were used as controls. Control cells were cultured and selected in the same way as those in experimental group. - Evaluation criteria:
- Not indicated
- Statistics:
- Statistically significant differences between treatment and control groups were determined at p<0.05 and p<0.01. The statistical test method chosen was not specified.
Results and discussion
Test results
- Key result
- Sex:
- female
- Genotoxicity:
- negative
- Toxicity:
- not examined
Any other information on results incl. tables
Treatment with Morpholine at 500 mg/kg bw induced no increases in chromosomal aberrations or frequency of micronuclei in primary embryonic cell cultures.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Under the conditions of this study, transplacental exposure to Morpholine did not induce genetic toxicity on the basis of chromosomal aberrations or micronuclei formation. - Executive summary:
In this transplacental mutagenesis study (Inui et al., 1979), sodium nitrite with Morpholine or Morpholine (500 mg/kg bw) alone were administered by single oral gavage to pregnant Syrian golden hamsters on day 11 or 12 of pregnancy. Twenty-four hours after treatment, the hamster embryos were excised and examined for chromosomal aberrations, micronucleus formation, morphological or malignant transformation and drug resistance mutation. Cells exposed in utero to Morpholine showed no increases in the numbers of chromosomal aberrations, micronuclei, 8 -azaguanine- or ouabain-resistant mutants, or transformation rates. The number of resistant colonies was markedly increased after administration of sodium nitrite together with Morpholine only, showing that Morpholine alone has no mutagenic effect in vivo under the conditions of this study. In this valid in vivo study there was no evidence for mutagenic effects of Morpholine over background.
This study is classified as acceptable.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.