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EC number: 902-591-9 | CAS number: -
- 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:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Toxicological Research of Methanol as a fuel for Power Station. Summary Report on Tests with Monkeys, Rats and Mice.
- Author:
- New Energy Development Organization
- Year:
- 1 987
- Bibliographic source:
- New Energy Development Organization, Tokyo
- Reference Type:
- publication
- Title:
- Long-term effects of methanol vapor at low concentration.
- Author:
- Takeda, K. and Katoh, N.
- Year:
- 1 988
- Bibliographic source:
- Proc. of the 8th Int. Symp. Alcohol Fuels, 1051-1056, Tokyo, Japan
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Deviations:
- yes
- Remarks:
- - limited documentation; copulation time was too long (21 days); not all parameters mentioned in the guideline were investigated
- 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:
- Methyl alcohol
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 8 weeks
- Diet: Solid Chow for rat (CRF-1, Charles River Japn Inc.)
- Water: Sterilised and filtrated water (ad libitum)
- Acclimation period: 10 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- 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: multi-stage inhalation chamber (Hazleton 1000 exposure chamber)
- Temperature, humidity in air chamber: 24 ± 2 °C; 55 ± 5 %
TEST ATMOSPHERE
- Nominal exposure levels were prepared by generating methanol gas and then mixing it with fresh air.
- A methanol gas analyser measured the concentration in the chamber. - Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 21 d
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Other: The pairs without evidence of insemination within 21 d were again cohabited with untreated animals (2nd mating) to determine the fertility of each animal, in this case without exposure (p.186). - 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 (the monthly variation remained less than 5 %).
- Duration of treatment / exposure:
- F0: 103 -108 d
F1: 61 -62 d and 145 -153 d
F2: 54 -56 d
for further informations see "any other information on materials and methods" - Frequency of treatment:
- continuously
- Details on study schedule:
- - F1 parental animals not mated until 12 weeks after selected from the F1 litters.
- Female F1 animals were examined for sexual cycle at 12-weeks or thereafter and mated with males of the same group.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.013 mg/L air
- Remarks:
- corresponding to 10 ppm
- Dose / conc.:
- 0.13 mg/L air
- Remarks:
- corresponding to 100 ppm
- Dose / conc.:
- 1.3 mg/L air
- Remarks:
- corresponding to 1000 ppm
- No. of animals per sex per dose:
- 30 (F0 generation)
Additionally, 15 animals were reared for a second mating. - Control animals:
- yes, sham-exposed
Examinations
- Parental animals: Observations and examinations:
- Observations of F0 and F1 parental animals.
CAGE SIDE OBSERVATIONS:
- Clinical signs, mortality, any sign of abortion and premature delivery
- Time schedule: At least once a day, 5 days a week
BODY WEIGHT:
- Time schedule for examinations: animals were weighed weekly: day 0, 7, 14 and 20 of gestation and day 0, 4, 7, 14 and 21 of delivery
FOOD AND WATER CONSUMPTION::
- Consumption measured by cage (on the same days as body weight measurements)
OTHER:
- Generally sexual cycle, mating time, fertility, pregnancy rate were documented. During the lactation period, maternal animals were observed for nursing behavior including lactation, nest building and presence/absence of pup-eating. - Sperm parameters (parental animals):
- Histological examination of morphology of sperms was not included.
- Litter observations:
- Observations of F1 and F2 litters.
Litters were examined on the day of birth for live pups, dead pups, sex and any external abnormalities. The observations were done daily until weaning and thereafter 5 days a week.
Each litter was weighed on day 0 and 4 (before reduction) of birth by sex and respective mean value calculated. After adjustment of litter size, pups were weighed individually on day 4, 7, 14 and 21. From weaning to week 14 of birth, the measurements were done weekly.
All surviving pups were observed for post-natal morphological differentiation indices: pinna unfolding, eruption of incisors, open eyes, descensus testis (males), vagina opening (females).
As for movement function test, all surviving pups after adjustment of litter size were tested for righting on a surface, ipsilateral flexor reflex, pinna reflex, auricular startle response, visual recognition response, pain response, corneal reflex and suspension abililty on a particular day before weaning. Also emotional tests, learning ability tests, and movement coordination tests were included.
In 9-week old F1 pups, blood methanol was measured, but not formate (p. 191). - Postmortem examinations (parental animals):
- Examinations of F0 and F1 parental animals.
After mating all males were necropsied, and testes, epididymis, seminal vesicle and postate gland were removed and preserved.
After 2 weeks of rearing, the females at the 2nd mating were necropsied and examined for pregnancy status. After termination of mating, the not inseminated females were necropsied and the ovary, uterus and bagina were preserved.
21 days after delivery, all dams were necropsied and examined for implantation. The vagina, uterus and ovary were preserved.
Any organ with any abnormality was subjected to a histopathological examination, if necessary.
26 days after evidence of insemination, females which had not yet delivered were necropsied and subjected to the same examinations as the above. - Postmortem examinations (offspring):
- Examinations of F0 and F1 litters.
After termination of movement function tests, pups were sacrificed and necropsied.
The pups which were selected for examination and not used for the movement function test were necropsied on a day of the same age at 8 weeks old or thereafter and principal organs were weighed. - Statistics:
- All data obtained were analysed by t-test, Fischer´s exact test, U-test of Mann-Whitney or Armitage´s chi²-test.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment-related alterations in general observations.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no differences for body weight.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There were no differences for food consumption.
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- There were no differences for water consumption.
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No abnormalities were observed in findings on nursing behavior.
- Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- None of the fertility indices including sexual cycle, days needed for insemination, insemination rate and pregnancy rate showed statistically significant differences.
No abnormalities were observed in findings on delivery and nursing behavior and necropsy data of F0 animals.
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1.3 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
Effect levels (P1)
- Key result
- Dose descriptor:
- NOAEC
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not measured/tested
Target system / organ toxicity (P1)
- Key result
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- In male pups of the 1.3 mg/L group, post-natal morphological differentiation appeared to be influenced with respect to the descensus tests occurring 0.5 to 1 d earlier (see same effect in F2 generation)[not mentioned by Takeda and Katoh, 1988]: This time-dependent parameter was evaluated by relating the completion of downward migration of the testes (final length of the gubernaculum reached) to the post-natal body-weight gain (The more reliable body length was not available):
In the F1 pups derived from the 1.3 mg/L group (108 males), this process was completed within 16 through 20 post-natal days with the climax at day 17 and 18 (32 and 39 %, respectively), while in the respective control (113 males), descent was complete from 16 through 21 days with the maximum at day 19 (32 %), but also relatively high percentages on the days before and after: day 18 (22%), day 17 (19%), day 20 (18%). - Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- 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:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Description (incidence and severity):
- None of the fertility indices including sexual cycle, mating time, fertility and pregnancy rate showed a significant difference from untreated F1 controls.
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute and relative brain weights were significantly lowered in the high-dose groups of either sex at an age of 8 and 16 weeks. This was still found in females necropsied after 24 weeks. Also other organs showed slight shifts in weights: thymus, pituitary (lower), heart, lung, liver (higher).
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Description (incidence and severity):
- no histopathological manifestations; no effects on testes or ovaries reported
- Other effects:
- no effects observed
- Description (incidence and severity):
- There were no significant differences in functional tests (movement, emotion, learning) as compared with the control or the other groups.
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- no effects observed
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Generation:
- F1
- Effect level:
- 0.13 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- other: reproductive parameter, brain weight
- Key result
- Dose descriptor:
- LOAEC
- Generation:
- F1
- Effect level:
- 1.3 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- other: reproductive parameter, brain weight
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- As in F1 males, an apparently dose-related earlier descensus testis was noted after 1.3 mg/L exposure: F2 (94 males) on day 16 (42%), day 17 (40%), day 18 (15%) vs. control (91 males) on day 16 (10%), day 17 (39%), day 18 (31%), day 19 (14%) (p. 200).After 0.13 mg/L, "descensus testis" in male F2-progeny was about 0.5 d earlier than in male control F2 pups (p. 195). Detailed data not specified and not addressed under "Discussion".
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- 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:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Organ weights showed similar tendencies as found in the F1-generation.
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Description (incidence and severity):
- no histological changes; no effects on testes or ovaries reported.
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Effect levels (F2)
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Generation:
- F2
- Effect level:
- 0.13 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- other: reproductive parameter, brain weight
- Key result
- Dose descriptor:
- LOAEC
- Generation:
- F2
- Effect level:
- 1.3 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- other: reproductive parameter, brain weight
Target system / organ toxicity (F2)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Blood levels of methanol measured in the F1-offsprings (age 9 weeks) (NEDO, 1987, p. 191):
controls (baseline): approx. 2 - 3 mg/L
0.013 mg/L methanol: approx. 3 - 3.5 mg/L
0.13 mg/L: approx. 1 - 4.2 mg/L
1.3 mg/L: approx. 53 (males)-100 (females) mg/L
There are no data on formate.
Note: Exposure per day was 20 h, which implies that prolonged steady-state blood levels were reached which even may have been higher than in studies using the same exposure concentration, but shorter exposure times.
Applicant's summary and conclusion
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.