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EC number: 205-745-7 | CAS number: 149-73-5
- 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
Trimethyl orthoformate did not induce a mutagenic effect in S. typhimurium, and is therefore not considered a bacterial mutagen.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002-02-14 to 2002-05-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Remarks:
- S. typhimurium TA102 is a valid alternative to E. coli WP2 uvrA
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- hisD3052, hisG46, hisG428 (paQ1), hisC3076
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 102
- Additional strain / cell type characteristics:
- other: contains R-factor plasmid pKM101
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 fraction (lot # 270701, RCC Cytotest Cell Research , Rossdorf, Germany) induced with phenobarbital + beta-naphthoflavone
- Test concentrations with justification for top dose:
- Test #AM-02/04.1: Plate incorporation test: 50, 160, 500, 1600, 5000 microgram/plate
Test #AM-02/04.2: Preincubation test: 50, 160, 500, 1600, 5000 microgram/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: miscible with test substance, compatible with the survival of the bacteria and S9 activity - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminofluorene and 2-aminoanthracene for all strains
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Test #AM-02/04.1: in agar (plate incorporation), Test #AM-02/04.2: preincubation
DURATION
- Preincubation period: 30 min
- Exposure duration: 72 hours at 37°
NUMBER OF REPLICATIONS: Triplicate, per strain and concentration of the test material
NUMBER OF CELLS EVALUATED: >7'100'000 per plate
DETERMINATION OF CYTOTOXICITY
- other: pre-experiment for toxicity (with strains TA 98 and TA 100) with seven concentrations (25 - 5000 microgram/plate) showed no signs of toxicity (reduction of background lawn) - Evaluation criteria:
- VALIDITY:
- Characteristic mean number of spontaneous revertants (of each strain) in solvent control
- Titers of overnight cultures > 100'000'000
- Significant increase in the number of revertants in the mean of each positive control, compared with the mean of the solvent control; exception: in case of no significant increase of revertants with 2-aminofluorene, a parallel significant increase with 2-aminoanthracene will be regarded as sufficient, and vice versa.
- At least four non-toxic dose levels
EVALUATION:
- At least a doubling in the mean revertants per plate of at least one tester strain (in two independent experiments)
- This increase must be accompanied by a dose response to increasing concentrations of the test article
- Single increases in revertant frequencies (not dose-related, not reproducible in independent tests) are considered non-relevant
- If such increases occur in both independent tests, this will be taken as an indication of a mutagenic effect - Statistics:
- Mean and standard deviation of replications
Test compound / control ratio: Mean no. of colonies/plate (test compound) / mean no. of colonies/plate (water) - 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- other: Positive controls valid, except 2-aminoanthracene; parallel 2-aminofluorene showed enough activity, therefore, condition for validity was met
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: not tested
- Effects of osmolality: not tested
- Evaporation from medium: not tested
- Water solubility: fully miscible, no effect
- Precipitation: not observed
- Other confounding effects: none
RANGE-FINDING/SCREENING STUDIES: Pretest (plate-incorporation test with strains TA 98 and TA 100 showed no toxicity and no induction of mutation.
COMPARISON WITH HISTORICAL CONTROL DATA: Based on tests performed 1998 - 2001 (TA 102: 1999 and 2001), only insignificant deviations were observed (one test higher, several tests lower). The results were regarded as acceptable.
ADDITIONAL INFORMATION ON CYTOTOXICITY: A reduced growth of the bacterial background lawn, indicative of test compound induced cytotoxicity, was not detectable with any of the tester strains. - Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Trimethyl orthoformate is not a bacterial mutagen.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- not explicitly stated
- Deviations:
- yes
- Remarks:
- Only strains TA97, TA98; TA100
- GLP compliance:
- yes
- Remarks:
- Quality assurance statement attached
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine gene, frame-shift or base-pair substitution
- Species / strain / cell type:
- S. typhimurium TA 97
- Additional strain / cell type characteristics:
- other: rfa character, presence of pKM101
- Species / strain / cell type:
- S. typhimurium TA 98
- Additional strain / cell type characteristics:
- other: rfa character, presence of pKM101
- Species / strain / cell type:
- S. typhimurium TA 100
- Additional strain / cell type characteristics:
- other: rfa character, presence of pKM101
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9 fraction induced with Aroclor-1254
- Test concentrations with justification for top dose:
- 8, 40, 200, 1000, 5000 microgram/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: not stated - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-acetylaminofluorene
- Remarks:
- With metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Preincubation period: none
- Exposure duration: at least 2 days
NUMBER OF REPLICATIONS: triplicate; negative and positive controls quintuplicate
NUMBER OF CELLS EVALUATED: not stated
DETERMINATION OF CYTOTOXICITY
- Method: other: inspection of the bacterial background lawn - Evaluation criteria:
- VALIDITY:
- Mean negative control counts within normal range (from historical solvent control values, tabulated in the report)
- Positive control chemicals induce clear increases in revertant numbers, confirming discrimination between different strains, and an active S9 preparation
- No more than 5% of the plates lost (through contamination or other cause); at no data point: all replicates lost
EVALUATION: A test compound was considered to be mutagenic if
- The assay was valid
- There were two-fold increases in revertant numbers, accompanied by significant F-statistics and dose-response correlations - Statistics:
- - Mean and standard deviation of the plate counts for each treatment
- Analysis of variance (F-test) and regression analysis, if a two-fold (or greater) increase in revertants over the solvent control is observed - Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: not tested
- Effects of osmolality: not tested
- Evaporation from medium: not tested
- Water solubility: fully miscible, no effect
- Precipitation: not observed
- Other confounding effects:
RANGE-FINDING/SCREENING STUDIES: Pretest (plate-incorporation) with strain TA 100 showed no signs of toxicity (with and without S9)
COMPARISON WITH HISTORICAL CONTROL DATA: Ranges for spontaneous revertants on solvent control plates from a large volume of historical control data tabulated in report and used for valididy assessment
ADDITIONAL INFORMATION ON CYTOTOXICITY: No signs of reduced growth of the bacterial background lawn, indicative of test compound induced cytotoxicity - Remarks on result:
- other: all strains/cell types tested
Referenceopen allclose all
In both experiments (test #AM-02/04.1: plate incorporation test; test #AM-02/04.2: preincubation test), the treatment with the test compound did not result in a dose-related significant increase in the revertant frequency in any of the five tester strains TA 98, TA 100, TA 102, TA 1535 and TA 1537, with or without metabolic activation by S9 mix.
All criteria for a valid study were met as described: All tested bacterial strains exhibited a positive mutagenic response with the positive controls (with and without metabolic activation; TA 102: only with 2-aminofluorene). Solvent controls (water) were also tested with each strain, and the mean numbers of spontaneous revertants were considered acceptable.
Trimethyl orthoformate did not induce a mutagenic effect in S. typhimurium, and is therefore not considered a bacterial mutagen.
Maximum increase of revertants over controls: 0.9 - 1.2 without metabolic activation, 1.0 - 1.3 with metabolic activation (in all strains)
Additional information
Ames test (bacterial reverse mutation in vitro): Negative
A key study conducted in 2002 according to guideline OECD 471 and under GLP is available. The study is considered to be relevant, reliable (Klimisch 1) and adequate for the purposes of risk assessment, classification and labelling. Five S. typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 were investigated; TA102 is listed as a valid alternative to E. coli WP2 uvrA or E. coli WP2 uvrA (pKM101), so that the requirements of the guideline are fully met. Trimethyl orthoformate did not elicit a mutagenic effect in any of the strains, with and without metabolic activation, and is therefore not considered a bacterial mutagen.
A supporting study (on 18 test substances, GLP, 1987) investigated only three S. typhimurium strains (TA97, TA98, TA 100), none of which showed any mutagenic response.
Chromosome aberration: No data available
Short description of key information:
Ames test (Infracor, Enste-Diefenbach 2002): negative (S.
typhimurium TA98, TA100, TA102, TA1535, TA1537)
Ames test (Microtest, Kenelly 1987): negative (S. typhimurium TA97,
TA98, TA100)
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
Both in vivo studies considered were negative and therefore do not warrant classification.
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