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EC number: 203-640-0 | CAS number: 109-02-4
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- The original study report is in Japanese language, although the figures and tables are in English. An English summary is available from the Japanese authorities and an extensive summary is present in the OECD HPV program files.
Data source
Referenceopen allclose all
- Reference Type:
- other: public database
- Title:
- Unnamed
- Year:
- 2 003
- Reference Type:
- other: public database
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
- Reference Type:
- grey literature
- Title:
- Unnamed
- Year:
- 2 004
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 4-ethylmorpholine
- EC Number:
- 202-885-0
- EC Name:
- 4-ethylmorpholine
- Cas Number:
- 100-74-3
- IUPAC Name:
- 4-ethylmorpholine
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): N-ethylmorpholine
- Molecular formula (if other than submission substance): C6 H13 N O
- Molecular weight (if other than submission substance): 115.18
- Smiles notation (if other than submission substance): CCN1CCOCC1
- InChl (if other than submission substance): InChI=1/C6H13NO/c1-2-7-3-5-8-6-4-7/h2-6H2,1H3
- Analytical purity: equal or more than 99%
- Impurities (identity and concentrations): 0.05% as moisture
- Lot/batch No.: 2901P0
- Stability under test conditions: The test solution was prepared and diluted to dosing concentrations by injection solvent every week. The diluted solution was confirmed to be stable for 8 days.
- Storage condition of test material: The test solution was kept in a refrigerator
Test animals
- Species:
- rat
- Strain:
- other: Crj:CD(SD)IGS
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals: Four weeks old Crj:CD(SD)IGS rats bought from Charles River Japan, Inc. They were put in quarantine and acclimatization for 7 days before use.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Vehicle: water for injection.
The test solution was prepared and diluted to dosing concentrations by injection solvent every week. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The dosing solutions were confirmed to be stable.
- Duration of treatment / exposure:
- Males: 42 days
Females: from 14 days before mating to day 3 of lactation - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- vehicle
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
- Positive control:
- None.
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes, on day 1, 7, 14, 21, 28, 35, 42, 43 (males). Females: on day 1, 7, 14 pre-mating, on day 0, 7, 14, 20 of pregnancy and on day 0 and 4 of lactation.
FOOD CONSUMPTION: Yes, on days 1-2, 7-8, 14-15, 29-30, 35-36, 41-42 (males). Females on days 1-2, 7-8, 14-15 pre-mating, on days 0-1, 7-8, 14-15, 20-21 of pregnancy and on days 3-4 of lactation.
ORGAN WEIGHTS: Yes - Oestrous cyclicity (parental animals):
- mean length of estrous cycle during treatment period and pre-treatment period, number of animals showing 4-day cycle during pre-treatment period, changes of estrous cycle after treatment, mean times of vaginal estrus during mating period.
- Sperm parameters (parental animals):
- absolute and relative weights of testes and epididymides.
- Litter observations:
- STANDARDISATION OF LITTERS
No pups were discarded.
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, weight gain - Postmortem examinations (parental animals):
- Examined
- Postmortem examinations (offspring):
- Examined
- Statistics:
- Methods by Dunnett, bartlett, Fischer, Mann-Whitney
- Reproductive indices:
- copulation index, fertility index, gestation index, indexes for implantation, delivery
- Offspring viability indices:
- indexes for birth and live birth
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Tremor was observed in the female which died, and transient salivation after dosing was observed in males and females at 150 mg/kg bw/day and higher.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- No deaths were found in males of any group. One female at 500 mg/kg bw/day died on day 2 of lactation.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decrease in body weight gain accompanied by reduced food consumption was detected in males at 500 mg/kg bw/day and females at 150 mg/kg bw/day and higher.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Decrease in body weight gain accompanied by reduced food consumption was detected in males at 500 mg/kg bw/day and females at 150 mg/kg bw/day and higher.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Histopathological examination of reproductive organs revealed no abnormalities related to dosing.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- No adverse effects on estrous cyclicity
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effects on copulation index, fertility index, precoital interval, gestation length, gestation index and number of corpora lutea.
Effect levels (P0)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- not examined
Details on results (F1)
external appearance, general conditions or necropsy findings in offspring of rats.
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects observed at highest dose tested.
Target system / organ toxicity (F1)
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The NOAELs for general toxicity in parent animals are considered to be 150 mg/kg bw/day in males and 50 mg/kg bw/day in females, based on reduced body weight gain and food consumption. The NOAEL for reproductive and developmental toxicity is considered to be 500 mg/kg bw/day.
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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