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EC number: 201-185-2 | CAS number: 79-20-9
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicological Research of Methanol as a Fuel for Power Station, Summary Report on Tests with Monkeys, Rats and Mice
- Author:
- NEDO
- Year:
- 1 987
- Bibliographic source:
- New Energy Development Organization, Tokyo, 1987
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- Not all parameters mentioned in the guideline were investigated, limited documentation
- Principles of method if other than guideline:
- According to national standards. Comprehensive study programme including metabolic, pharmacokinetic, short-, long-term, reproduction and carcinogenicity studies.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Methanol
- EC Number:
- 200-659-6
- EC Name:
- Methanol
- Cas Number:
- 67-56-1
- Molecular formula:
- CH4O
- IUPAC Name:
- methanol
- Details on test material:
- TS-Freetext:
Methanol, reagent special grade from Junsei Chemicals Co.,
<1 ppm vinyl chloride, <3 ppm formaldehyde
------------------
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 12 weeks
- Diet: Solid Chow for rat (CRF-1, Charles River Japn Inc.)
- Water: sterilised and filtrated water (ad libitum)
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2 °C
- Humidity (%): 55 ± 15 %
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: H 1000 multi-tiered inhalation chambers, Hazleton Systems Inc., USA (volume 2.5 m³)
- Method of holding animals in test chamber: pregnant females were individually housed in wire mash stainless steel cages with 24 rooms placed in the inhalation chamber (whole body exposure)
- Source and rate of air: filtered external air, ventilation rate of 30 (not further specified)
- Method of conditioning air: passed through a medium performance filter, a high performance filter and an activated carbon filter
- System of generating vapours: total vaporizer supplied with liquid methanol by a microprecision pump, vaporization into the filtered air
- Temperature, humidity, pressure in air chamber: 23-26°C, 50-65%, atmospheric pressure
- Air flow rate: 1250 L/min
- Air change rate: 30/h
- Method of particle size determination: not applicable
- Treatment of exhaust air: not specified
TEST ATMOSPHERE
- Brief description of analytical method used: air from the inhalation chamber was extracted at a rate of 1.0 L/min by a sampling apparatus and the methanol concentration measured by a methanol vapor analyzer incorporating an infra-red spectrophotometer. The concentration signal was transmitted to the microprecision pump and used to regulate the methanol concentration in the chamber by adjusting liquid flow.
- Samples taken from breathing zone: no - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical concentration values of methanol were close to nominal ones.
- Details on mating procedure:
- Impregnation procedure: pregnant females, not further specified
- Duration of treatment / exposure:
- gestation day 7 - 17
- Frequency of treatment:
- Animals were exposed to methanol gas continuously except during routine procedures such as observations and examinations.
Care was taken to ensure equal exposure time for all groups including the control. - Duration of test:
- various durations: until Cesarian section, the age of 8 weeks, and reproduction of F1, respectively
Doses / concentrationsopen allclose all
- Dose / conc.:
- 270 mg/m³ air
- Dose / conc.:
- 1 330 mg/m³ air
- Dose / conc.:
- 6 650 mg/m³ air
- No. of animals per sex per dose:
- 36 dams per test and control group, including 12 dams allowed for natural delivery.
- Control animals:
- yes, concurrent no treatment
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION: Yes
WATER CONSUMPTION: Yes
POST-MORTEM EXAMINATIONS: Yes - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Other: embryolethality - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes - Statistics:
- All the data obtained were analyzed by t-test, U-test of Mann-Whitney, Fisher's exact test or Armitage's chi2 - test.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the high-dose group, one dam died, another one had to be killed before delivery.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A decrease in body-weight gain at 5000 ppm
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption was reduced during gd 7 through 12 at 5000ppm
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Drinking water consumption was reduced during gd 7 through 12 at 5000ppm
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- late resorptions: 10.4 % vs. 0.6 % in control, p<0.05 at 5000 ppm, but the variance between single litters was high
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- effects observed, treatment-related
- Description (incidence and severity):
- After 5000 ppm, mean gestation time was prolonged by 0.7 days.
- Changes in number of pregnant:
- not examined
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1.33 mg/L air
- Based on:
- test mat.
- Basis for effect level:
- early or late resorptions
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 6.65 mg/L air
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- early or late resorptions
- food consumption and compound intake
- mortality
- water consumption and compound intake
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weight of live fetuses after Cesarian section was reduced (about -20 %, p<0.001) at 5000 ppm.
Also after birth, body weight gain values of high-dose group (in both males and females) tended to be lower than control values.
Particularly in females, significant differences were noted throughout the period after weaning and obvious depression of body weight gain was present. In males, however, it was of smaller extent significant differences were noted up to Week 5 of birth (after weaning) but not thereafter.
These F1 animals were all small in size and showed decrease in milk consumption and depressed vitality. - Reduction in number of live offspring:
- effects observed, treatment-related
- Description (incidence and severity):
- in the high-dose group (5,000 ppm), cases of death occurred in many litters during Days 0 - 4 of birth, which resulted in significantly lower survival rate of pups for this interval.
- Changes in postnatal survival:
- effects observed, treatment-related
- Description (incidence and severity):
- In the high-dose group (5,000 ppm), cases of asthenia and death occurred in many litters during Days 0 - 4 of birth, which resulted in significantly lower survival rate of pups for this interval. ln addition, all cases of death occurred within the day of birth in the other groups, while it continued to occur on and after Day 1 of birth in this group and there were cases, though very limited in number, showing a depression of vitality even on Day 4 of birth.
On and after Day 4 of birth (the day of litter size adjustment), however, there was no more case of death even in the high-dose (5,000 ppm) group, and no case which had abnormal appearance, either. - External malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- One fetus each of the mid-dose (1,000 ppm) and high-dose group (5,000 ppm) had systemic edema. There was no other fetus having any external malformation.
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The high-dose group (5,000 ppm) showed a delay for almost all ossification parameters. Delay with significant difference was noted for body of cervical vertebrae, upper incisor, metacarpals and proximal phalanx of front limbs: "atresia of cervical vertebrae foramen costotransversarium" (45 %), " bifurcated vertebral centra" (14 %) and "cervical rib" (65 %) as well as "excessive sublingual neuropore" (50 %), all of which malformations having no or little relevance in the other group except of "atresia foramen" with about 25 % in the control and about 4 to 8 % in the other exposure groups
- Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- In the high-dose group (S,000 ppm), about one-half of the fetuses (visceral malformation in 16/20 litters or 64/131 fetuses) showed ventricular septal defect. This malformation was observed in 80% (16/20) of litters. Except for 5 fetuses (3 litters) having exeessive left subclavian artery, no other significant difference was noted.
As for variation, fetuses having residual thymus increased (variation in all 20 litter or 70/131 fetuses) and fetuses having serpenginous urinary duct decreased. The differences were significant for both the variations. - Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Post-natal morphological differentiation:
In pups from the 5000-ppm group, eruption of upper incisor and opening of eyelid for both sexes and descensus testis for males were significantly earlier than in the controls in relation to term of delivery, but not in relation to the whole gestation time which was prolonged for this group.
There were no differences in behavioral and functional tests as compared to control and other test groups. Reflex reaction, emotional (open field test), learning ability (pole-climbing test) and movement coordination (rotor rod test) did not show any treatment-related change.
At the age of 8 weeks, brain, thyroid (males), thymus and testis (males) weights were lower (p<0.01), and pituitary-gland weight of males was higher (p<0.05). But histological examination revealed no treatment-related changes. 16.5 % of the offsprings (15/91 in 8/12 litters) had hemilateral thyroprivia (missing thyroid lobe, mostly left). There was no histopathological lesion in the tissue. The defect was attributed to an impairment of organogenesis.
Reproductive performances of F1 (from 5000 ppm):
No significant effects on sexual cycle, genital function and reproductive performance of the F1 progeny were noted.
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1.33 mg/L air
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- changes in postnatal survival
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: Teratogenic effects occurred only at maternally toxic exposure concentration.
- Dose descriptor:
- LOAEC
- Effect level:
- 6.65 mg/L air
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- changes in postnatal survival
- skeletal malformations
- visceral malformations
Fetal abnormalities
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- other: visceral and skeletal malformations, postnatal growth and survival
- Description (incidence and severity):
- Teratogenic effects occurred only at maternally toxic exposure concentration
Overall developmental toxicity
- Key result
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 6.65 mg/L air
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- yes
Applicant's summary and conclusion
- Conclusions:
- Pregnant rats were exposed to 0, 200, 1000 and 5000 ppm of methanol by inhalation during fetal organogenesis (days 7 - 17 of gestation). The exposure to 5000 ppm produces maternal toxicity, fetal malformation, increased perinatal mortality and developmental delay in surviving progeny. Teratogenic effects occurred only at maternally toxic exposure concentration. Exposure levels of 1000 ppm or less did not induce toxic symptoms in maternal animals, structural abnormalities or delay in growth or functional development in the F1-generation. Therefore, the NOEC for maternal and developmental toxicity is considered to be 1000 ppm.
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