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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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Methanol has been examined in numerous tests including bacterial, mammalian and fungal test systems. Most studies produced consistently negative results, with four exceptions.
Link to relevant study records
- Endpoint:
- genetic toxicity in vitro, other
- Remarks:
- Type of genotoxicity: genome mutation in fungi
- 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
- Principles of method if other than guideline:
- Determination of chromosomal malsegregation in ascomycetes during mitosis induced by test substance application.
- GLP compliance:
- not specified
- Type of assay:
- other: Mitotic recombination in ascomycetes
- Target gene:
- not applicable
- Species / strain / cell type:
- other: Aspergillus nidulans diploid strain P1
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 5.2, 5.6, 6.0, 7.0 % (v/v)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Key result
- Species / strain:
- other: Aspergillus nidulans diploid strain P1
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 7.0 % (lowest concentration to arrest conidial germination)
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- not specified
- Additional information on results:
- For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: genome mutation
Type of study: other: Mitotic recombination in ascomycetes
Guideline:
Species/strain (Method):
- other: Aspergillus nidulans diploid strain P1 - Conclusions:
- Interpretation of results:
positive - Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- 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
- Principles of method if other than guideline:
- The endpoint of the test was cytotoxicity due to chromosome damage. The ratio of the minimal inhibitory concentration (MIC) of repair proficient to the MIC of repair-deficient E. coli strains was taken as an indicator for genotoxicity.
- GLP compliance:
- not specified
- Type of assay:
- other: DNA damage and repair assay in bacteria
- Target gene:
- not applicable
- Species / strain / cell type:
- E. coli WP2
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- other: wild-type, repair proficient
- Species / strain / cell type:
- E. coli, other: WP67
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- other: repair deficient: uvrA-, polA-
- Species / strain / cell type:
- E. coli, other: CM871
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- other: repair deficient: uvrA-, recA-, lexA-
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- No details: the initial concentration was governed by the solubility or by the toxicity of the TS as inferred from preliminary testing. Starting from this, eight 2-fold dilution steps followed in general.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium and 2-h preincubation:
Trials were conducted in miniature form (liquid micromethod procedure: 350 μl) using microwell plates that contained nutrient broth, and as 2-h preincubation assay ("treat-and-plate method" on nutrient broth agar).
DURATION
- Preincubation period: 2 h
- Exposure duration: 16 h (liquid micromethod procedure)
DETERMINATION OF CYTOTOXICITY
- Method: other: determination of the Minimal Inhibitory Concentration (MIC): growth retardation - Evaluation criteria:
- For each tester strain, the Minimal Inhibitory Concentration (MIC) was determined. The endpoint was cytotoxicity due to chromosome damage. The ratio of the MIC of the repair proficient to the MIC of the repair deficient strains was taken as indicator for genotoxicity. A ratio of greater than 2 was accepted as significant only if reproducible in 5 parallel independent experiments.
- Key result
- Species / strain:
- E. coli, other: WP2, WP67, CM871
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 40 mg/well
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- E. coli, other: WP67, CM871
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 20 mg/well
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 40 mg/well
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: not specified
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: not specified
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: DNA damage and/or repair
Type of study: other: DNA damage and repair assay in bacteria
Guideline:
Species/strain (Method):
- E. coli WP2
- E. coli, other: WP67
- E. coli, other: CM871 - Remarks on result:
- other: other: microwell method
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
ambiguous - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Remarks:
- limited documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Only strains TA97 and TA102 tested
- Principles of method if other than guideline:
- According to Maron and Ames, 1983.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-operon
- Species / strain / cell type:
- S. typhimurium TA 97
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 102
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with
- Metabolic activation system:
- S9 mix from Aroclor-induced SD rat livers
- Test concentrations with justification for top dose:
- <= 7.5 mg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
- Evaluation criteria:
- Positive response: dose response relationship, revertant ratio >=2.
- Key result
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Remarks:
- slightly positive trend
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: gene mutation
Type of study: bacterial reverse mutation assay (e.g. Ames test)
Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Species/strain (Method):
- S. typhimurium TA 97
- S. typhimurium TA 102 - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Principles of method if other than guideline:
- Optimisation of the amount of S9-mix to be used to obtain maximum yield of mutations. Comparative study including typical mutagens. According to Clive and Spector (1975), Mutat Res 31: 17-29.
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidin-kinase
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with
- Metabolic activation system:
- Aroclor 1254-induced rat liver S9-mix
- Test concentrations with justification for top dose:
- 7.9 mg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: no data
- Details on test system and experimental conditions:
- DURATION
- Exposure duration: at least 4 h
SELECTION AGENT (mutation assays): TFT (trifluorothymidine) - Evaluation criteria:
- Significant increases in mutation frequency with the test substance
- Statistics:
- no data
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: gene mutation
Type of study: mammalian cell gene mutation assay
Guideline:
Species/strain (Method):
- mouse lymphoma L5178Y cells - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
positive - Endpoint:
- in vitro cytogenicity / micronucleus study
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Test procedure in accordance with accepted standard methods, sufficiently documented, acceptable for assessment.
- Principles of method if other than guideline:
- In vitro micronucleus test with V79 cells comparing alcohols, acetone and various alkylating agents.
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian cell micronucleus test
- Target gene:
- not applicable
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 50 µL/mL (approx. 40 mg/mL)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: medium (Eagle's MEM + 10 % FCS), acetone for positive controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
- Remarks:
- 0, 0.02, 0.04, 0.08 µg/mL; solvent acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- 0, 0.4, 2, 10, 50, 100 µg/mL; solvent acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- 0, 25, 50, 100 µg/mL; solvent acetone
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 48 h
STAIN (for cytogenetic assays): 4% Giemsa
NUMBER OF REPLICATIONS: not reported
NUMBER OF CELLS EVALUATED: 7000 interphase cells at each concentration used
OTHER
Cells were plated at a density of 13000 cells/cm², incubated for 15-18 h, then treated with the test substance. After treatment, the cells were incubated for 48 h, then collected, subjected to hypotonic treatment with KCl, fixed with acetic acid-methanol, and then stained with 4% Giemsa. - Evaluation criteria:
- Criteria used to score MN: (1) staining intensity equal to that of the nucleus, (2) diameter less than one-fifth that of the nucleus, (3) location in cytoplasm, (4) no contact with nucleus to distinguish from nuclear blebs.
- Statistics:
- The dose response was estimated by linearr regression curves. Difference in the sensitivity of mutagenic compounds was established by comparing the slopes of corresponding dose-response regression curves. For a comparison of mean values, Student's t test was used.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results (migrated information):
negative - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study, also largely meeting current standards, sufficient documentation, acceptable for assessment.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- Exposure and expression period combined
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- HPRT
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- no data
- Test concentrations with justification for top dose:
- 15.8, 31.7, 47.4, 63.3 mg/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: culture medium (Eagle's MEM)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-dimethylnitrosamine
- Remarks:
- with S9 Migrated to IUCLID6: 1 and 2 mg/mL
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: MNNG, 0.29 and 0.59 µg/mL
- Remarks:
- without S9
- Details on test system and experimental conditions:
- DURATION
- Exposure duration: 6 days
- Expression time (cells in growth medium): combined with 6 days exposure
- Selection time (if incubation with a selection agent): after 6 days
SELECTION AGENT (mutation assays): 8-Azaguanin, 6-Thioguanin, Ouabain
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency (colony formation) - Evaluation criteria:
- Significant increase in V79 cells resistant to 8-Azaguanine, 6-Thioguanine or Ouabain.
- Statistics:
- Calculation of mean mutation frequency±S.D. per 10e6 surviving cells.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 63.3 mg/ml (approx. 70 % inhibition of colony formation)
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results (migrated information):
negative - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-operon, Trp-operon (E. coli)
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1538
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Liver S9 fraction of KC500-pretreated rats
- Test concentrations with justification for top dose:
- 5, 10, 50, 100, 500, 1000, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.01 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA100
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- both 5.0 µg/plate, respectively
- Positive control substance:
- other: N-ethyl -N'-nitro-N-nitrosoguanidine (ENNG) without S9, 2-aminoanthracene (2AA) with S9
- Remarks:
- TA1535both 5.0 µg/plate, respectively
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.05 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, 2-aminoanthracene (2AA) with S9
- Remarks:
- WP2 uvrA
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.05 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA98
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 80.0 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 9-aminoacridine (9AC) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA1537
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 0.25 and 5.0 µg/plate, respectively
- Positive control substance:
- other: 4-nitroquinoline-1-oxide (4NQO) without S9, benzo(a)pyrene (B(a)P) with S9
- Remarks:
- TA1538
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: duplicates
DETERMINATION OF CYTOTOXICITY
- Method: other: growth inhibition of revertant clones - Evaluation criteria:
- Doubling of revertant numbers in comparison to control and dose-response correlation.
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: gene mutation
Type of study: bacterial reverse mutation assay (e.g. Ames test)
Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Species/strain (Method):
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- S. typhimurium TA 1538
- E. coli WP2 uvr A - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- 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
- Remarks:
- limited documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Salmonella TA102 and/or E.coli WP2 missing
- Principles of method if other than guideline:
- according to Ames et al., 1975.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His-operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1538
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix from Aroclor-induced SD rat livers
- Test concentrations with justification for top dose:
- <= 2.5 mg/plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- non-toxic within the range of testing
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- non-toxic within the range of testing
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- For the phrase selection in field 'Endpoint' the following source information was used as basis:
Type of genotoxicity: gene mutation
Type of study: bacterial reverse mutation assay (e.g. Ames test)
Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Species/strain (Method):
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- S. typhimurium TA 1538 - Conclusions:
- Interpretation of results:
negative
Referenceopen allclose all
There was a concentration-related increase in non-disjunctions (chromosomal malsegregation) with a maximum of about 3 %. No aneuploidies were noted at the lowest test concentration. The result was statistically significant at two concentrations and a dose-response relationship was evident (IPCS/WHO 1997).
No other forms of malsegregation were statistically significant (1/265 cross-over seen at 6.0 %). The survival was reduced in dose-related manner.
Survival and amount of aneuploidy in Aspergillus nidulans after methanol-treatment:
Concentration [%] |
Survival [%] |
Scored colonies |
Aneuploids (yellow segregants) |
|
counts |
[%] |
|||
5.2 |
26 |
268 |
0 |
0 |
5.6 |
19 |
407 |
6 |
1.47* |
6.0 |
10 |
265 |
8 |
3.02** |
7.0 |
5 |
176 |
0 |
0 |
Spontaneous control |
||||
0 |
100 |
2673 |
7 |
0.26 |
* P<0.01; ** P<0.001
Note: Similar results were obtained with ethanol and other primary aliphatic alcohols. The aneuploidy rate of ethanol reached a maximum of about 10 %.
The microwell method resulted in a negative result in the presence of S9 and in a positive result in the absence of S9 at 20 mg/well (Flora et al., 1990, 1984). But the preincubation procedure was negative without S9, but ambiguous with S9 (Flora et al. 1984).
Note: The MIC concentrations were very high (40 and 20 mg/well = about 120 g/L and 60 g/l).
Given the high concentrations and the conflicting findings, it is concluded that observations made at the margin of significance (ratio = 2) are of low reliability and biological relevance. The weak relative increase of toxicity in repair-deficient strains may be an increase in unspecific cytotoxicity rather than solely "genotoxicity". (Note: A similar result was obtained with ethanol at somewhat lower concentrations).
In TA102, a slightly positive trend was indicated [(±) ambiguous], reproducible in 5 parallel independent experiments, but never exceeding the revertant ratio of 2: Spontaneous mutation rate 200 - 300/plate, while in the presence of high methanol doses, an increase in the mutation frequency above background of 140 revertants was found.
The methanol-related increase in the mutation frequency in TA102 did not fulfil the accepted criteria for mutagenic activity. Along with the high methanol doses required to induce such a weak effect and the negative results observed in all other Ames tests, the overall evidence clearly demonstrates that methanol is not mutagenic in bacterial reverse-mutation systems.
In the presence of 10 - 15 µL/mL S9 and methanol (7.9 mg/mL), there was a significant increase in mutation frequency. No detailed results presented.
No MN increases induced by any alcohol or acetone, whereas the alkylating agents produced significant MN frequencies above medium controls.
|
Max. number of MN/1000 cells [mean±S.E.] |
|
|
Control (solvent dose) |
Chemical (dose) |
Methanol |
4.00±0.71 (50 µL/mL) |
3.50±1.19 (50 µL/mL) |
MNNG |
3.2±0.40 (5 µL/mL) |
8.2±0.83 (0.08 µg/mL) |
MMS |
3.9±0.59 (5 µL/mL) |
16.5±0.50 (100 µg/mL) |
EMS |
2.2±0.40 (5 µL/mL) |
7.0±0.69 (100 µg/mL) |
Solvent for methanol: medium
Solvent for MNNG, MMS, EMS: acetone
The test substance induced no increases in mutant frequency in gene mutation to drug resistance vs. negative control, whereas the positive control DMN produced increases in dose-related manner in the presence of metabolic activation (S9 mix), and MNNG in the absence of metabolic activation.
Maximum mutation frequency of V79 cells (per 10e6 survival cells, mean±SD) for resistance towards 6-TG, 8-AG and Ouabain after methanol treatment:
|
Control |
Test substance (mg/mL) |
||
Selectant |
-S9 |
+S9 |
-S9 |
+S9 |
6-Thioguanine |
0.70±1.79 |
0.94±2.18 |
1.55±3.08 (47.4 mg/mL) |
0.84±2.21 (31.7 mg/mL) |
8-Azaguanine |
23.42±8.70 |
24.29±7.30 |
22.34±7.39 (31.7 mg/mL) |
20.05±13.01 (31.7 mg/mL) |
Ouabain |
1.23±2.23 |
0 |
2.64±2.79 (47.7 mg/mL) |
0.11±0.36 (47.7 mg/mL) |
Maximum number of revertants:
|
Control (water) [mean±SD] |
Test substance (µg/plate) |
||
Strain |
-S9 |
+S9 |
-S9 |
+S9 |
TA100 |
149±17.1 |
161±16.2 |
175 (100) |
180 (50) |
TA1535 |
28±6.9 |
15±3.6 |
35 (50) |
17 (5000) |
TA98 |
29±6.2 |
39±8.6 |
42 (50) |
39 (1000) |
TA1537 |
16±6.4 |
21±8.1 |
22 (5000) |
35 (5) |
TA1538 |
21±5.5 |
28±7.0 |
18 (500) |
31 (5) |
E.coli WP2 uvrA |
32±7.3 |
33±10.3 |
36 (5000) |
43 (10) |
The test substance was not mutagenic in the tested strains up to 5000 µg/plate.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Description of key information
The available in vivo assays are negative for mutagenicity and clastogenicity.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- restriction: only one sampling time
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- - limited documentation, only one sampling time
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Route of administration:
- intraperitoneal
- Duration of treatment / exposure:
- one single injection
- Frequency of treatment:
- only one sampling time
- Post exposure period:
- 30 h
- Remarks:
- Doses / Concentrations:
1920; 3200; 4480 mg/kg
Basis:
nominal conc. - No. of animals per sex per dose:
- 2
- Control animals:
- yes
- Tissues and cell types examined:
- bone-marrow cells
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Conclusions:
- Interpretation of results: negative
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- 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
- Principles of method if other than guideline:
- This study was performed to determine whether MeOH could indirectly DNA damage via ROS-mediated mechanism. Animals (mice, rabbits and monkeys) were treated with either once or for 15 days with 2.0 g/kg MeOH i.p.. Oxidative DNA damage was observed by measuring 8-oxo-2'-deoxyguanosine. Lipid peroxidation in bone marrow and spleen homogenates was determined by measuring the Ievels of HNE-His protein adducts.
- GLP compliance:
- not specified
- Type of assay:
- other: oxidative DNA damage
- Species:
- other: mouse, rabbit, monkey
- Strain:
- other: CD-1, New Zealand white, cynomolgus
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: mice, rabbits and monkeys: Charles River Laboratories
- Age at study initiation: mice: 9 - 13 weeks; rabbits: 5 months; monkeys: 3.4 - 5.7 years
- Weight at study initiation: rabbits: 3.25 - 3.75 kg, monkeys: 2.8 - 4.8 kg
- Diet: mice: rodent chow ad libitum; rabbit: standard high-fiber rabbit chow; monkeys: certified primate chow diet (# 5048) from Purina Mills (St. Louis, MO) supplemented with fruit or vegetables 2-3 times weekly
- Water: mice, rabbit and monkeys: ad libitum
- Acclimation period: monkeys: two weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): mice and rabbits: 20°C; monkeys: 18 - 29°C
- Humidity (%): mice: 50%, rabbits: 60%
- Photoperiod (hrs dark / hrs light): mice: 10/14; rabbits and monkeys: 12/12 - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: saline
- Details on exposure:
- Mice: Drugs were administered via intraperitoneal (ip) injection using a 26 gauge (G) 3/8 needle.
Rabbits: by ip injection usinga 23 G needle
monkeys: were lightly sedated with ketamine (ca. 5 - 10 mg/kg) for dose administration and then administered MeOH (2g/kg bw; 20% [w/v] in sterile saline) or a saline vehicle by ip injection using a 22G needle. - Duration of treatment / exposure:
- single or 15 consecutive days
- Frequency of treatment:
- daily
- Post exposure period:
- 6 hours or 15 days
- Remarks:
- Doses / Concentrations:
2 g/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- Three rabbits and primates were used in each treatment group. Four and five mice were used in each group for the acute and chronic studies, respectively.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- KBrO3
- Justification for choice of positive control(s): is a known renal carcinogen
- Route of administration: i.p.
- Doses / concentrations: 100 mg/kg bw at a fixed volume of 0.1 mL/10g bw - Tissues and cell types examined:
- DNA from spleen and bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: The effect of a Iimit dose of 2.0 g/kg bw MeOH based on guidelines established for the comet assay developed in accordance with the in vivo genetic toxicology guidelines of the Organization for Econornic Co-operation and Development (OECD) were studied.
METHOD OF ANALYSIS: DNA was isolated using DNAzol, a novel guanidine-detergent lysing solution that hydrolyzes RNA and allows for the selective precipitation of DNA from cell lysates. 8-oxodG and dG were analysed via HPLC system. Lipid peroxidation in bone marrow and spleen homogenates was determined by measuring the Ievels of HNE-His protein adducts. - Statistics:
- Statistical analysis was performed using GraphPad Instat Version 3.05 (GraphPad Software, lnc., San Diego, CA). Experiments comparing two groups were analyzed by unpaired t tests and multiple comparisons were anaJyzed by one-way ANOVA followed by a Tukey post-test. The Ievel of significance was set at P<0.05.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not examined
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- No increase in oxidative DNA damage was observed in bone marrow or spleen at 6 h following exposure to MeOH (2.0g/kg bw ip) in mice, rabbits,
or primates. Similarly, no increase in oxidative DNA damage was observed in bone marrow or spleen 24 h following exposure to a single dose of MeOH (2.0g/kg bw ip), or following 15 consecutive daily doses of 2.0g/kg bw ip MeOH in CD-1 mice. No increase in HNE-His protein adducts was observed in bone marrow or spleen at 6 h following exposure to MeOH (2.0 g/kg bw ip) in primates. MeOH exposure (2.0 g/kg bw ip) increased HNE-His protein adducts 1.4-fold 6 h post-dose in bone marrow of mice, with adduct Ievels returning to basal values within 24 h. No increases in HNE-His protein adducts were observed in spleen of mice or bone marrow of rabbits following MeOH exposure (2.0 g/kg bw ip). MeOH exposure (2.0 g/kg bw ip) increased HNE-His protein adducts 1.5-fold 6 h post-dose in spleen of rabbits. - Conclusions:
- Interpretation of results: negative
Taken together these observations suggest that it is unlikely that exposure to MeOH would initiate Iymphomas, particularly in humans, via formation
of mutagenic oxidative DNA lesions. - Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- 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
- Remarks:
- missing positive control
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- Mammalian chromosome aberration test performed with primary lung cells cultured after inhalation exposure.
- GLP compliance:
- not specified
- Type of assay:
- chromosome aberration assay
- Species:
- mouse
- Strain:
- other: C57BL/6J
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 10 weeks old
- Housing: Mice were housed in an animal facility in laminar-flow rooms
- Diet (e.g. ad libitum): Purina rodent chow
- Water (e.g. ad libitum): tap water
ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 15 cycles/hour of biocleaned air
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation: vapour
- Vehicle:
- none
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: whole body
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure: Methanol was vaporised and transported by nitrogen and HEPA-filtered air to stainless steel chambers.
- Air flow rate: 105 L/min
- Air change rate: 15 air changes/hours
TEST ATMOSPHERE
- Brief description of analytical method used:
Chamber methanol concentrations, monitored continuously by a Foxboro Miran 1A Infrared Analyser, indicated that ppm levels did not differ by more than 7% from calculated values. - Duration of treatment / exposure:
- 5 days
- Frequency of treatment:
- 6 h/day
- Post exposure period:
- no
- Remarks:
- Doses / Concentrations:
1.04 or 5.3 mg/L (corresponding to 800 or 4000 ppm)
Basis:
nominal conc. - No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Positive control(s):
- No positive control group was concomitantly examined. Historical positive control are available.
- Tissues and cell types examined:
- primary cultures of lung cells
- Details of tissue and slide preparation:
- Immediately following the last exposure, animals were anesthetised and blood was removed by perfusion, the lungs were infused with a trypsin, EDTA and collagenase solution; and then removed, minced and incubated in the same enzyme solution. The cells were collected and culture dishes with 160,000 viable cells per animal were established. One hundred first-division metaphases per animal were examined for CA. Aberrations were classified separately by type (chromatid or chromosome) and analysed as rearrangement or breakage events. The replication indices were estimated from 200 metaphases per animal. The number of metaphases per 1000 consecutive cells was also counted for determination of mitotic indices.
- Statistics:
- A 1- way analysis of variance was performed with Statgraphics statistical package. CA data were then analysed by a 1-tailed Dunnett´s test.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- There was no evidence of induced chromosome aberrations in lung cells.
- Toxicity:
- no effects
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- not examined
- Positive controls validity:
- other: only historical positive controls
- Additional information on results:
- No increase in the frequency of aberrations per cell and percent aberrant cells and no toxic effects were induced by the treatment:
Aberration rate per cell (including chromatid and chromosome breakage as well as rearrangement events) was from 0.04 to
0.07 in treated animals vs. 0.09 in the control group. The few aberrations found were mostly chromatid-type breaks or fragments.
Percentages of cells with abnormal chromosomes were not significantly different among treated and control groups within an experiment (6.9 % vs. 6.2 % (for 4000 ppm) and 3.8 % vs. 3.8 % (800 ppm). The replicative and mitotic indices were not significantly different from the controls. - Conclusions:
- Interpretation of results: negative
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- 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
- Remarks:
- missing positive control
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- Spermatocytes of the pachytene substage of the meiotic prophase after 5 days of last exposure were isolated and morphological parameters concerning the meiotic chromosome structure were examined.
- GLP compliance:
- not specified
- Type of assay:
- chromosome aberration assay
- Species:
- mouse
- Strain:
- other: C57BL/6J
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 10 weeks old
- Housing: Mice were housed in an animal facility in laminar-flow rooms
- Diet (e.g. ad libitum): Purina rodent chow
- Water (e.g. ad libitum): tap water
ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 15 cycles/hour of biocleaned air
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation: vapour
- Vehicle:
- none
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: whole body
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure: Methanol was vaporised and transported by nitrogen and HEPA-filtered air to stainless steel chambers.
- Air flow rate: 105 L/min
- Air change rate: 15 air changes/hours
TEST ATMOSPHERE
- Brief description of analytical method used:
Chamber methanol concentrations, monitored continuously by a Foxboro Miran 1A Infrared Analyser, indicated that ppm levels did not differ by more than 7% from calculated values. - Duration of treatment / exposure:
- 5 days
- Frequency of treatment:
- 6 h/day
- Post exposure period:
- 5 days
- Remarks:
- Doses / Concentrations:
1.04 or 5.3 mg/L (corresponding to 800 or 4000 ppm)
Basis:
nominal conc. - No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Positive control(s):
- No positive control group was concomitantly examined.
- Tissues and cell types examined:
- Spermatocytes of the pachytene substage of the meiotic prophase 5 days after last exposure
- Details of tissue and slide preparation:
- Spermatocytes of the pachytene substage of the meiotic prophase after 5 days of last exposure were isolated, and fixed for electronmicroscopy: Several morphological parameters concerning the meiotic chromosome structure were examined (synaptonemal complex analysis).
- Statistics:
- A 1- way analysis of variance was performed with Statgraphics statistical package. SC data were then analysed by a 1-tailed Dunnett´s test.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- No increased frequencies of synaptonemal complex damage in spermatocytes were found.
- Toxicity:
- not specified
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Additional information on results:
- Methanol did not produce significant dose-dependent increases in SC aberrations.
- Conclusions:
- Interpretation of results: negative
Referenceopen allclose all
There was no significant effect on the frequency of micronuclei in treated as compared to control animals: 1.3/1000 (control and low dose), 2.0/1000 (2nd dose), and 3.7/1000 (top dose).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In vitro studies:
Methanol has been examined in numerous tests including bacterial, mammalian and fungal test systems. Most studies failed to demonstrate mutagenic activity, with four exceptions: 1) in Salmonella tester strain TA 102, a questionable positive response was observed (DeFlora et al., 1984a); 2) in a DNA damage and repair assay with E. coli WP strains (repair proficient and deficient types), the result was considered ambiguous (DeFlora et al. 1984b); 3) in a mouse-lymphoma assay, a significant increase in the mutation rate was reported at 7.9 mg/mL methanol (McGregor et al., 1985); and 4) in a test of mitotic chromosomal segregation in Aspergillus nidulans, a positive result was observed (Crebelli et al., 1989). All other studies produced consistently negative results (Shimizu et al., 1985; DeFlora, 1981; NEDO, 1987; Lasne et al., 1984).
In vivo studies:
The available in vivo assays are negative for mutagenicity and clastogenicity. Some of these assays were conducted under specific stress conditions using folate-deficient mice (Am. Petrol. Inst., 1991; Fu, 1996).
In conclusion, the majority of in vitro and in vivo assays on methanol are negative for mutagenicity and clastogenicity. However, a few of the in vitro assays were positive or ambiguous (DeFlora et al., 1984a, 1984b; McGregor et al., 1985; Crebelli et al., 1989). The positive findings can not be evaluated since the available data base is limited.
Short description of key
information:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): S.
typhimurium negative except TA 102+S9 (ambiguous) (OECD 471)
Gene mutation (Mammalian cell gene mutation assay): V79 negative,
L5178Y+S9 positive (both comparable to OECD 476)
Chromosome aberration (in vitro micronucleaus assay): V79 negative
DNA damage (Damage and repair assay in bacteria): E. coli positive
Genome mutation (Mitotic chromosomal segregation assay): A. nidullans
positive
In vivo:
Chromosome aberration (Chromosomal aberration): primary lung cells
negative
Chromosome aberration (Micronucleus assay): erythrocytes negative
(similar OECD 474), primary lung cells negative
Chromosome aberration (Synaptonemal complex): pachytene spermatocytes
negative
Justification for classification or non-classification
Classification,
Labelling, and Packaging Regulation (EC) No 1272/2008
The
available experimental test data are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. Based on
th negative results in the in vivo studies, methanol does not appear
to be mutagenic. As
a result the substance is not considered to be classified for genetic
toxicity under Regulation (EC) No 1272/2008, as amended for the tenth
time in Regulation (EU) No 2017/776.
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