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EC number: 473-370-8 | 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The substance (in DMSO) was tested in the Ames test in Salmonella typhimurium strains TA 1535, TA1537, TA98 and TA100 and in E.coli strain WP2uvrA at concentrations of 3 to 5000 ug/plate with and without metabolic activation.
No cytotoxicity or precipitate was observed up to 5000 ug/plate. The number of revertants was not increased in any of the evaluated concentrations (100 -5000 ug/plate). Vehicle and positive controls included gave results within the historical control ranges. An independent repeat with the same evaluated concentrations gave a similar result. It is therefore concluded that the substance is not mutagenic in bacteria with and without metabolic activation.
In a chromosome aberration assay the substance was tested in 2 independent assays with and without metabolic activation.
In the first assay human peripheral lymphocytes were exposed during 3 hours (24 fixation time with colchicine added 2.5 -3 h before fixation) in absence and presence of metabolic activation at concentrations of 333, 1000 and 1612 ug/mL (highest dose is 0.01 M). No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
In the second assay human peripheral lymphocytes were exposed during 24 hours (24 h fixation time with colchicine added 2.5 -3 h before fixation) in absence of metabolic activation at concentrations of 100, 200, 400, 600, 800,1000, 1200, 1400 and 1612 ug/mL Based on mitotic index the concentrations evaluated were 100, 200 and 600 ug/mL. No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
In an addtional assay human peripheral lymphocytes were exposed during 48 hours (48 h fixation time with colchicine added 2.5 -3 h before fixation) in absence of metabolic activation at concentrations of 33, 100, 300, 400, 500, 600, 700, 800, 900 and 1000 ug/mL. Based on mitotic index the concentrations evaluated were 100, 200 and 600 ug/mL. No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
In another assay human peripheral lymphocytes were exposed during 3 hours (48 fixation time with colchicine added 2.5 -3 h before fixation) with metabolic activation at concentrations of 333, 1000 and 1612 ug/mL (highest dose is 0.01 M). No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
It can be concluded that the substance is not clastogenic.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06 February 2007 to 19 February 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- His+ (S. typhimurium), Trp+ (E. coli)
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- source of S9 : liver of phenobarbital/beta-naphthoflavone (80/100 mg/kg bw) treated rats
- method of preparation of S9 mix (10 mL): A mixture of 30 mg NADP and 15.2 mg glucose-6-phosphate dissolved in 5.0-5.5 mL Milli-Q water, 2 mL 0.5 M sodium phosphate buffer, 1 mL 0.08 M MgCl2 and 1 mL 0.33 M KCl was filter (0.22 um) sterilized. To this 0.5 to 1 mL S9 homogenate was added
- concentration or volume of S9 mix and S9 in the final culture medium : experiment 1 5%, experiment 2 10% - Test concentrations with justification for top dose:
- experiment 1: 3, 10, 33, 100, 333, 1000, 3330 and 5000 ug/plate with and without metabolic activation (evaluated concentrations 100-5000 ug/plate)
experiment 2: 100, 333, 1000, 3330 and 5000 ug/plate with and without metabolic activation
Maximum concentration based on the absence of toxicity (bacterial background lawn, size of micro colonies and number of revertants) and precipitate in a dose range finding study in TA100 and TA98 at 3, 10, 33, 100, 333, 1000, 3330 and 5000 ug/plate with and without metabolic activation - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- methylmethanesulfonate
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplcate
- Number of independent experiments : 2
METHOD OF TREATMENT/ EXPOSURE:
- Cell density: 1.0E09 cells/mL
- Test substance in agar (plate incorporation)
TREATMENT AND HARVEST SCHEDULE:
- Exposure duration/duration of treatment: 48 hours
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: background growth inhibition; size of micro-colonies and number of revertants
METHODS FOR MEASUREMENTS OF GENOTOXICIY :
TA100 number of revertants >2 times vehicle control
TA98, TA1535, TA1537 and Wp2uvrA number of revertants >3 times vehicle control
Negative response confirmed in separate experiment
- Evaluation criteria:
- TA100 number of revertants >2 times vehicle control
TA98, TA1535, TA1537 and Wp2uvrA number of revertants >3 times vehicle control
Negative response confirmed in separate experiment - Statistics:
- NA
- Species / strain:
- S. typhimurium TA 1535
- 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
- Remarks:
- within historical control ranges
- Positive controls validity:
- valid
- Remarks:
- within historical control ranges
- Species / strain:
- S. typhimurium TA 1537
- 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
- Remarks:
- within historical control ranges
- Positive controls validity:
- valid
- Remarks:
- within historical control ranges
- 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
- Remarks:
- within historical control ranges
- Positive controls validity:
- valid
- Remarks:
- within historical control ranges
- 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
- Remarks:
- within historical control ranges
- Positive controls validity:
- valid
- Remarks:
- within historical control ranges
- Species / strain:
- E. coli WP2 uvr A
- 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
- Remarks:
- within historical control ranges
- Positive controls validity:
- valid
- Remarks:
- within historical control ranges
- Conclusions:
- The substance is not mutagenic in bacteria with and without metabolic activation
- Executive summary:
The substance (in DMSO) was tested in the Ames test in Salmonella typhimurium strains TA 1535, TA1537, TA98 and TA100 and in E.coli strain WP2uvrA at concentrations of 3 to 5000 ug/plate with and without metabolic activation.
No cytotoxicity or precipitate was observed up to 5000 ug/plate. The number of revertants was not increased in any of the evaluated concentrations (100 -5000 ug/plate). Vehicle and positive controls included gave results within the historical control ranges. An independent repeat with the same evaluated concentrations gave a similar result.
It is therefore concluded that the substance is not mutagenic in bacteria with and without metabolic activation.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20 October 2007 to 19 December 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- NA
- Species / strain / cell type:
- lymphocytes: primary lymphocytes
- Details on mammalian cell type (if applicable):
- CELLS USED
- Type and source of cells: human peripheral lymphocytes
- Suitability of cells: standard according to the guideline
For lymphocytes:
- Sex, age and number of blood donors:
range finding: male 37 years, AGT 14.5 h
1st exp: male 30 years, AGT 13.5 h
2nd exp: male 40 years, AGT 13.9 h
- Whether whole blood or separated lymphocytes were used: whole blood treated with heparine
- Mitogen used for lymphocytes: phytohaemagglutinin
MEDIA USED : RPMI1640 medium supplemented with 20% v/v foetal calf serum, L-glutamine, penicillin/streptomycin and 30U/mL heparin
CO2 concentration 5 mg/L, humidity level 66-91%, temperature 34.8-37.4 ˚C (deviations were evaluated as of no influence on the study result). - Cytokinesis block (if used):
- colchicine
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- source of S9: liver of phenobarbital/beta-naphthoflavone (80/100 mg/kg bw) treated rats
- method of preparation of S9 mix: A mixture in 0.5 M sodium phosphate buffer of 3.4 mg/mL NADP, 1.7 mg/mL glucose-6-phosphate, 1.63 mg/mL MgCl2, 2.46 mg/mL KCl and 4 umol HEPES was filter (0.22 um) sterilized. To this 0.5 to 1 mL S9 homogenate was added
- concentration or volume of S9 mix and S9 in the exposure medium: 1.8 %v/v - Test concentrations with justification for top dose:
- exp 1: with and without S9: 333, 1000 and 1612 ug/mL (highest dose is 0.01 M)
exp 2: with S9: 333, 1000 and 1612 ug/mL (highest dose is 0.01 M)
without S9 24 exposure: 100, 200, 400, 600, 800,1000, 1200, 1400 and 1612 ug/mL (based on mitotic index evaluated concentrations selected were 100, 200 and 600 ug/mL)
without S9 48 exposure: 33, 100, 300, 400, 500, 600, 700, 800, 900 and 1000 ug/mL (based on mitotic index evaluated concentrations selected were 100, 500 and 600 ug/mL) - Vehicle / solvent:
- DMSO (HBBS for positive controls)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: duplicate
- Number of independent experiments : 2
METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in medium
TREATMENT AND HARVEST SCHEDULE:
- Preculture for 48 hours
- Exposure duration/duration of treatment: exp 1: 3 h (24 h fixation time)
exp 2: with S9 3 h (48 h fixation time); without S9 24 h (24 h fixation time), 48 h (48 h fixation time)
FOR CHROMOSOME ABERRATION AND MICRONUCLEUS:
- Spindle inhibitor (cytogenetic assays): colchicine (0.5 ug/mL medium) at 2.5-3 hours before fixation
- Methods of slide preparation and staining technique: cultures were centrifuged (1300 rpm) and the supernatant was discarded, The cells were swollen during 5 min with potassium chloride and fixed with 3 changes of methanol. Fixed cells were dropped on slides (2/culture) and stained with Giemsa during 10-30 min.
- Number of cells spread and analysed per concentration: 100 metaphases per culture were analysed for chromosomal aberrations by light microscopy (1000 metaphases were counted for assessment of mitotic index)
- Determination of polyploidy: included, but none found
- Determination of endoreplication: included, but none found
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method, mitotic index (MI) - Evaluation criteria:
- positive: if it induced a dose-related statistically significant increase in the number of chromosomal aberration compared with the concurrent negative control; if a statistically significant and biologically relevant increase in the number of chromosomal aberrations is observed without dose-response relationship
- Species / strain:
- lymphocytes: huma
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Remarks:
- in all 3 h experiments
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Remarks:
- 24 h exposure cytotoxicity at 800 ug/mL, 48 h exposure cytotoxicity at 600 ug/mL
- Positive controls validity:
- valid
- Additional information on results:
- details see attached tables
- Conclusions:
- The substance did not induce chromosomal aberrations in presence and absence of metabolic activation
- Executive summary:
In a chromosome aberration assay the substance was tested in 2 independent assays with and without metabolic activation.
In the first assay human peripheral lymphocytes were exposed during 3 hours (24 fixation time with colchicine added 2.5 -3 h before fixation) in absence and presence of metabolic activation at concentrations of 333, 1000 and 1612 ug/mL (highest dose is 0.01 M). No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
In the second assay human peripheral lymphocytes were exposed during 24 hours (24 h fixation time with colchicine added 2.5 -3 h before fixation) in absence of metabolic activation at concentrations of 100, 200, 400, 600, 800,1000, 1200, 1400 and 1612 ug/mL Based on mitotic index the concentrations evaluated were 100, 200 and 600 ug/mL. No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
In an addtional assay human peripheral lymphocytes were exposed during 48 hours (48 h fixation time with colchicine added 2.5 -3 h before fixation) in absence of metabolic activation at concentrations of 33, 100, 300, 400, 500, 600, 700, 800, 900 and 1000 ug/mL. Based on mitotic index the concentrations evaluated were 100, 200 and 600 ug/mL. No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
In another assay human peripheral lymphocytes were exposed during 3 hours (48 fixation time with colchicine added 2.5 -3 h before fixation) with metabolic activation at concentrations of 333, 1000 and 1612 ug/mL (highest dose is 0.01 M). No increase of the number of aberrations was seen at any of the concentrations tested. Vehicle (DMSO) and positive controls were within the expected ranges.
It can be concluded that the substance is not clastogenic.
Referenceopen allclose all
see attached document
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
Based on the available information the substance does not need to be classified for mutagenicity according to EU Regulation 1272/2008 (CLP).
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.
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