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EC number: 200-659-6 | CAS number: 67-56-1
- 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:
- 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:
- Influence of dietary folic acid on the developmental toxicity of methanol and the frequency of chromosomal breakage in the CD-1 mouse.
- Author:
- Fu, S.S., Sakanashi, T.M., Rogers, J.M., Keen, C.L.
- Year:
- 1 995
- Bibliographic source:
- Teratology 51, 162-163
- Reference Type:
- publication
- Title:
- Influence of dietary folic acid on the developmental toxicity of methanol and the frequency of chromosomal breakage in the CD-1 mouse.
- Author:
- Fu, S.S., Sakanashi, T.M., Rogers, J.M., Hong, K.H., Keen, C.L.
- Year:
- 1 996
- Bibliographic source:
- Reprod. Toxicol. 10, 455-463
- Reference Type:
- publication
- Title:
- Folate deficiency alone does not produce neural tube defects in mice.
- Author:
- Heid, M.K. et al.
- Year:
- 1 992
- Bibliographic source:
- J. Nutr. 122, 1198-1200
- Reference Type:
- publication
- Title:
- Plasma formate levels in methanol treated dams are not markedly influenced by dietary folate.
- Author:
- Hong, K.H., Sakanashi, S.S., Fu, S.S., Rogers, J.M., Keen, C.L.
- Year:
- 1 997
- Bibliographic source:
- Teratology Society Abstract 55, 57
Materials and methods
- Principles of method if other than guideline:
- Treatment of pregnant female mice on GD 6-10 with test substance by oral administration twice daily, investigation of the influence of folate in the diet on incidence of developmental defects in the offspring.
- GLP compliance:
- not specified
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
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles Rivers, Inc., Gilroy, CA
- Age at study initiation: 8 weeks
- Weight at study initiation: group weights on GD0 (mean ± SEM): 25.72 ± 0.48 to 27.19 ± 0.73 g
- Fasting period before study: no data
- Housing: stainless steel wire-bottomed cages
- Diet: amino-acid based, folic-acid free diet supplemented with either 400 or 1200 nmol folic acid/kg diet and 1 % succinylsulfathiazole for 5 weeks prior to mating and throughout breeding and gestation
- Water (e.g. ad libitum): no data
- Acclimation period: 5 weeks (already fed with special diet during this period)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 50
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- other: not applicable
- Vehicle:
- water
- Details on exposure:
- VEHICLE
- Concentration in vehicle: 15.65 % in deionized water
- Amount of vehicle (if gavage): no data - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/2 or 1/3
- Length of cohabitation: 12 h
- Further matings after two unsuccessful attempts: no (second breeding period was continued for up to 10 days)
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- GD 6-10
- Frequency of treatment:
- twice daily 2500 mg/kg bw
- Duration of test:
- until GD 18
Doses / concentrations
- Dose / conc.:
- 5 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 21 to 24 dams per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: knowledge from previous experiments
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: GD 0, 5, 10, 12, 15, 18
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 18
- Organs examined: liver, kidney, gravid uterus, blood (plasma and hematocrit, folate concentrations, MN formation in maternal reticulocytes) - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: fetal weights, crown-rump lengths, fetal liver folate concentrations, fetal hematocrit, MN formation in fetal reticulocytes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: No - Statistics:
- The pregnant dam and the litter were considered the units for comparisons. Continuous variables were analyzed using the two-way analysis of variance procedure and the Fisher PLSD for multiple comparisons of means. These analyses were carried out on STATVIEW SE+ (Abacus, Berkeley, CA). Incidences of fetal malformations and frequency of micronuclei, based on affected litters, were analyzed using binomial statistics.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- 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
- 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:
- not examined
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined - Changes in number of pregnant:
- not examined
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 5 000 mg/kg bw/day (nominal)
- Basis for effect level:
- other: maternal toxicity
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- reduced mean fetal weight and reduced mean crown-rump length
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined - Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- not specified
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- skeletal abnormalities (cleft palate, exencephaly)
- Visceral malformations:
- not examined
Effect levels (fetuses)
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 5 000 mg/kg bw/day (nominal)
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Key result
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- external: cranium
Overall developmental toxicity
- Key result
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 50 000 mg/kg bw/day (nominal)
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects in the absence of maternal toxicity effects
- Dose response relationship:
- not specified
Any other information on results incl. tables
A. Folate levels (measured on gd 18, 8 d after the final methanol treatment):
Low-folate diet produced a decline in folate in the maternal liver (total folate approx. -30%), in maternal plasma (approx. -30%), in maternal erythrocytes (approx. -30%) vs. normal-folate diet and in the fetal liver (approx. -60 to -70%) (Fu et al., 1996).
Methanol had no marked influence on maternal and folate levels irrespective of folate supplementation, except in maternal plasma where there was some evidence of a reduction of about 20 % . Methanol treatment was slighty fetotoxic (reduced mean fetal weight and reduced mean crown-rump length), but had no impact other reproductive parameters. It showed some evidence of a teratogenic effect (increased incidences of cleft palate and exencephaly) under folate-adequate supply, but this was hardly statistically significant: cleft palate (2/222 vs. 0/282) and execephaly (5/222 vs. 1/282 in the respective high-folate control).
Likewise, folate deficiency failed to produce significant malformations (in accordance with previous reports: e.g. Heid et al., 1992): cleft palate (5/215 vs. 0/282) and execephaly (2/215 vs. 1/282 in the respective high-folate control). However, cleft palate, but not exencephaly was significantly increased in the presence of methanol: 39/235 vs. 5/215 and 8/235 vs. 2/215 of folate-poor control, respectively. Methanol did not induce micronuclei in maternal or fetal blood.
B. In pregnant CD-1 mice given methanol (5 g/kg/d) from gestation day 6 - 15, one group receiving folate deficient, the other folate supplemented diet, there were no differences in the formate-blood levels between both groups: 5.13 +-0.68 mmol/L (folate-def.) and 3.90 +-0.94 mmol/L (folate-suppl.) vs. 0.36 +-0.13 mmol/L (untreated control). But developmental toxicity was significantly higher in folate-deficient dams (Hong et al. 1997). The results indicate that increased plasma formate levels in dams do not underlie the increased developmental toxicity of methanol in mice fed low dietary folate (Hong et al. 1997).
CONCLUSION:
Folate deficiency enhanced the teratogenic effects of methanol in mice.
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