Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 922-153-0 | 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
Genetic Toxicity in vitro - Bacterial
reverse mutation assay (OECD TG 471)
Genetic Toxicity in vitro - In vitro Mammalian Chromosome Aberration
Test (OECD TG 473) - Read-Across from C9 Aromatics
Genetic Toxicity in vitro - In vitro Mammalian Cell Gene Mutation Test
(OECD TG 476) - Read-Across from C9 Aromatics
Genetic Toxicity in vitro - In vitro Sister Chromatid Exchange Assay in
Mammalian Cells (OECD TG 479) - Read-Across from C9 Aromatics
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to OECD 471 guidelines. GLP.
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- 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:
- S9 liver fractions from Aroclor exposed rats
- Test concentrations with justification for top dose:
- Tests (done in triplicate) with and without Metabolic Activation: 0, 32, 63, 125, 250, 500 ug/plate
Positive controls:
TA 1535 (S9-: sodium azide 1.0 ug/plate) (S9+: 2-aminoanthracene: 2.0 ug/plate)
TA 1537 (S9-: 9-aminoacridine 80 ug/plate) (S9+: benzo(a)pyrene: 4.0 ug/plate)
TA 98 (S9-: 2-nitrofluorene 2.0 ug/plate) (S9+: 2-aminoanthracene: 2.0 ug/plate)
TA 100 (S9-: sodium azide 1.0 ug/plate) (S9+: 2-aminoanthracene: 2.0 ug/plate)
WP2 uvr A (S9-: N-ethyl-N-nitrosourea 100 ug/plate) (S9+: 2-aminoanthracene: 80 ug/plate) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- no
- True negative controls:
- yes
- Remarks:
- non treated
- Positive controls:
- yes
- Positive control substance:
- other: See Test Concentrations
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar
DURATION
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS:
- triplicate
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants and/or clearing of the background lawn of bacterial growth - Evaluation criteria:
- The mutagenicity study is considered valid if the mean colony counts of the control values of the strains are within acceptable ranges, if the positive controls meet the criteria for a positive response and if no more than 5% of the plates are lost through contamination or other unforeseen events.
A test substance is considered to be positive in the bacterial gene mutation test if the mean number of revertant colonies on the test plates increase in a concentration-related manner and/or if a reproducible two-fold or more increase is observed compared to that on the negative control plates.
A test substance is considered negative in the bacterial gene mutation test if it produces neither a dose-related increase in the mean number of revertant colonies nor a reproducible positive response at any of the test points.
Positive results from the bacterial reverse mutation test indicate that a substance induces point mutations by base substitution or frameshifts in the genome of Salmonella typhimurium. Negative results indicate that under the test conditions, the test substance is not mutagenic. - Statistics:
- The mean plate count and standard deviation for each dose point were determined. Any test value that was equal to or greater than two times the mean value of the concurrent vehicle control was considered to be a positive dose.
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Toxicity pretest was performed from doses of 556, 1667, 5000 ug/plate using all strains. Toxicity was observed at all of these doses and in phase 2 of the study, the doses were reduced to 0, 32, 63, 125, 250, 500 ug/plate.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results: negative
In all cases, the test material did not induce any significant changes in the number of revertant colonies. It is concluded in this study that the test material is not a mutagenic agent and is not classified under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP). - Executive summary:
Test material was examined for mutagenic activity in the bacterial reverse mutation test using histidine-requiring Salmonella typhimurium strains TA 1535, 1537, 98, and 100, and the E. coli strain WP2 uvr A in the absence and presence of a liver S9 fraction for metabolic activation. Concentrations above 500 ug/plate were found to be cytotoxic and so the test was performed in triplicate using doses of 0, 32, 63, 125, 250, 500 ug/plate. In all cases, the test material did not induce any significant changes in the number of revertant colonies. It is concluded in this study that the test material is not a mutagenic agent and is not classified under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).
- 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:
- 1998/11/05-1999/01/25
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to OECD 471 guidelines. GLP.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 liver fractions from Aroclor exposed rats
- Test concentrations with justification for top dose:
- Tests (done in triplicate) with and without Metabolic Activation: 0, 6.25, 12.5, 25, 50, 100, 200 ug/plate
Positive controls:
TA 1535 (S9-: sodium azide 1.0 ug/plate) (S9+: 2-aminoanthracene: 2.0 ug/plate)
TA 1537 (S9-: 9-aminoacridine 80 ug/plate) (S9+: benzo(a)pyrene: 4.0 ug/plate)
TA 98 (S9-: 2-nitrofluorene 2.0 ug/plate) (S9+: 2-aminoanthracene: 2.0 ug/plate)
TA 100 (S9-: sodium azide 1.0 ug/plate) (S9+: 2-aminoanthracene: 2.0 ug/plate)
TA102 (S9-: glutaraldehyde 25 ug/plate) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Remarks:
- non treated
- Positive controls:
- yes
- Positive control substance:
- other: See Test Concentrations
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar
DURATION
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS:
- triplicate
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants and/or clearing of the background lawn of bacterial growth - Evaluation criteria:
- The mutagenicity study is considered valid if the mean colony counts of the control values of the strains are within acceptable ranges, if the positive controls meet the criteria for a positive response and if no more than 5% of the plates are lost through contamination or other unforeseen events.
A test substance is considered to be positive in the bacterial gene mutation test if the mean number of revertant colonies on the test plates increases in a concentration-related manner and/or if a reproducible, two-fold or more increase is observed compared to that on the negative control plates.
A test substance is considered negative in the bacterial gene mutation test if it produces neither a dose-related increase in the mean number of revertant colonies nor a reproducible positive response at any of the test points.
Positive results from the bacterial reverse mutation test indicate that a substance induces point mutations by base substitution for frameshifts in the genome of Salmonella typhimurium. Negative results indicate that under the test conditions, the test substance in not mutagenic. - Statistics:
- The mean plate count and standard deviation for each dose point were determined. Any test value that was equal to or greater than two times the mean value of the concurrent vehicle control was considered to be a positive dose.
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Toxicity was observed at doses above 200 ug/plate with and without S9.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results: negative
In all cases, Shellsol AB did not induce any significant changes in the number of revertant colonies. It is concluded in this study that Shellsol AB is not a mutagenic agent. - Executive summary:
Shellsol AB was examined for mutagenic activity in the bacterial reverse mutation test using histidine-requiring Salmonella typhimurium strains TA 1535, 1537, 98, 102,and 100 in the absence and presence of a liver S9 fraction for metabolic activation. Concentrations above 200 ug/plate were found to be cytotoxic and so the test was performed in triplicate using doses of 0, 6.25, 12.5, 25, 50, 100, 200 ug/plate. In all cases, Shellsol AB did not induce any significant changes in the number of revertant colonies. It is concluded in this study that Shellsol AB is not a mutagenic agent.
- 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:
- 1991/01/28-1991/03/07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to OECD 471 guidelines. GLP.
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Not applicable
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 liver fractions from Aroclor exposed rats
- Test concentrations with justification for top dose:
- Tests (done in triplicate) with and without Metabolic Activation: 0 (DMSO or Acetone), 3.2, 10, 32, 100, 320 ug/plate
Vehicle control: 0.1 ml/plate DMSO (positive controls) or 0.1 ml/plate acetone (test material)
Positive controls: 5ug/plate 2AA, 10ug/plate MNNG, 100ug/plate 9AA, 5ug/plate 2NF - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO/ acetone
- Justification for choice of solvent/vehicle: Positive controls dissolved into DMSO, Test substance soluble in acetone - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- 0.1 ml/plate DMSO; 0.1 ml/plate Acetone
- True negative controls:
- yes
- Remarks:
- non treated
- Positive controls:
- yes
- Positive control substance:
- other: TA 1537 (+S9 2-aminoanthracene) TA 1537 (-S9 9-aminoacridine); TA 98 (-S9 2-nitrofluorene) (+S9 2-aminoanthracene); TA100 (-S9 MNNG) (+S9 2-aminoanthracene); TA1535 (-S9 MNNG) (+S9 2-aminoanthracene); TA138(-S9 2-Nitrofluorene) (+S9 2-aminoanthracene)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar
DURATION
- Exposure duration: 48 hours
NUMBER OF REPLICATIONS:
- triplicate
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants and/or clearing of the background lawn of bacterial growth - Evaluation criteria:
- The mutagenicity study is considered valid if the mean colony counts of the control values of the strains are within acceptable ranges, if the positive controls meet the criteria for a positive response and if no more than 5% of the plates are lost through contamination or other unforeseen events.
A test substance is considered to be positive in the bacterial gene mutation test if the mean number of revertant colonies on the test plates increases in a concentration-related manner and/or if a reproducible two-fold or more increase is observed compared to that on the negative control plates.
A test substance is considered negative in the bacterial gene mutation test if it produces neither a dose-related increase in the mean number of revertant colonies nor a reproducible positive response at any of the test points.
Positive results from the bacterial reverse mutation test indicate that a substance induces point mutations by base substitution for frameshifts in the genome of Salmonella typhimurium. Negative results indicate that under the test conditions, the test substance is not mutagenic. - Statistics:
- The mean plate count and standard deviation for each dose point were determined. Any test value that was equal to or greater than two times the mean value of the concurrent vehicle control was considered to be a positive dose.
- 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 nor precipitates, but tested up to recommended limit concentrations
- Remarks:
- not cytotoxic up to 10,000ug/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Toxicity pretest was performed from doses of 1 to 10000ug/plate using TA98. Toxicity was observed and a maximum dose of 320 ug/plate was selected.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results: negative
In all cases, MRD-90-884 did not induce any significant changes in the number of revertant colonies. It is concluded in this study that MRD-90-884 is not a mutagenic agent and is not classified under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP). - Executive summary:
MRD-90-884 was examined for mutagenic activity in the bacterial reverse mutation test using histidine-requiring Salmonella typhimurium strains TA 1535, 1537, 1538, 98, and 100 in the absence and presence of a liver S9 fraction for metabolic activation. Concentrations above 320 ug/plate were found to be cytotoxic and so the test was performed in triplicate using doses of 0, 3.2, 10, 32, 100, 320 ug/plate. In all cases, MRD-90-884 did not induce any significant changes in the number of revertant colonies. It is concluded in this study that MRD-90-884 is not a mutagenic agent and is not classified under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Source of data is from peer reviewed literature. Acceptable well-documented study report which meets basic scientific principles: GLP.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- CHO-K1-BH4 clone
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from livers of aroclor-induced Sprague-Dawley rats
- Test concentrations with justification for top dose:
- 15.0, 30.1, 45.0, 0.0, 75.0, 90.0 μg/ml without metabolic activation
20.0, 25.0, 37.5, 40.1, 50.0, 60.1, 70.0, 80.2 μg/ml with metabolic activation - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- other: MMC (unactivated cultures) and CP (metabolic activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in suspension
DURATION
- Exposure duration: 7 hrs (w/o activation); 2.5 hrs (w/ activation)
- Expression time (cells in growth medium): After 10 hour incubations, metaphase cells were collected by mitotic shake off
- Fixation: methanol:glacial acetic acid (3:1), stained with 5% Giemsa (pH 6.8)
Positive Controls: MMC (unactivated cultures) and CP (metabolic activation) - Evaluation criteria:
- Treatment groups were evaulated for overall chromosomal aberration frequency, the percentage of cells with aberrations, the percentage of cells with more than one aberration, the presence or absence of a dose-response and the complexity of the aberrations.
- Statistics:
- Fisher’s exact test with an adjustment for multiple comparisons to compare the percentage of cells with aberrations in each treatment group with the results from the controls (Sokal and Rohlf, 1981).
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- cytotoxic at 90.2 ug/mL with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- There were no increases in chromosomal aberrations at any concentration level tested in either the presence or absence of metabolic activation.
- Conclusions:
- Interpretation of results: negative
The test material is not clastogenic, however, it is cytotoxic at concentrations of 80.2 μg/ml or above. - Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Source of data is from peer reviewed literature. Acceptable well-documented study report which meets basic scientific principles: GLP.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- Method was according to:
Hsie, AW, Brimer, PA, Mitchell, TJ, and Gosslee, DG. (1975) Dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxyanthine-guanine phosphoribosyl transferase locus in Chinese hamster overy cells. Somat. Cell Genet. 1:247-261
Hsie, AW, Casciano, DA, Couch, DB, Krahn, DF, O'Neill, JP, and Whitfield, BL. (1981). The use of Chinese hamster ovary cells to quantify specific locus mutation and to determine mutagenicity of chemicals. Mutation Res. 86:193-214.
Myhr, BC and DiPaolo, JA. (1978). Mutagenesis of Chinese hamster cells in vitro by combination treatments with methyl methanosulfonate and N-acetoxy-2-acetylamino-fluorene. Cancer Res. 38: 2539-2543. - GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- CHO-K1-BH4 clone
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from livers of aroclor-induced Sprague-Dawley rats
- Test concentrations with justification for top dose:
- 0.01, 0.02, 0.04, 0.06, 0.07, 0.08, 0.1, 0.13 μl/ml without metabolic activation
0.02, 0.04, 0.06, 0.08, 0.1, 0.13, 0.16, 0.2 μl/ml with metabolic activation - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO 10 μl/ml
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: methylmethanesulfonate at 15 and 20 μl/ml, 5-bromo-2'-deoxyuradine at 50 μl/ml, 3-methylcholanthrene 5 μl/ml
- Remarks:
- without metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in suspension
DURATION
- Exposure duration: 4 hrs
- Expression time (cells in growth medium): 7 days
- Fixation time (start of exposure up to fixation or harvest of cells): 14 days
SELECTION AGENT (mutation assays): 4 micrograms/ml 6-thioguanine - Evaluation criteria:
- Treatment groups were evaulated for relative survival, relative population growth, absolute cloning efficiency, and mutation frequency.
- Statistics:
- Kastenbaum, MA, Bowman, KO. (1970). Tables for determining the statistical significance of mutation frequencies. Mutat. Res. 9: 527-549.
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cytotoxic at concentrations =>0.1 microliters/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Additional information on results:
- There was no evidence of mutagenicity as compared to controls.
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:negative
The test material is not mutagenic, however, it is cytotoxic at concentrations of 0.1 μl/ml or above. - Executive summary:
The test material is not mutagenic, however, it is cytotoxic at concentrations of 0.1 μl/ml or above.
- Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Source of data is from peer reviewed literature. Acceptable well-documented study report which meets basic scientific principles: GLP.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
- GLP compliance:
- yes
- Type of assay:
- sister chromatid exchange assay in mammalian cells
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from livers of aroclor-induced Sprague-Dawley rats
- Test concentrations with justification for top dose:
- 2.0, 6.67, 20.0, 35.0, 50.1, 66.7 μg/ml without metabolic activation
0.667, 2.0, 6.67, 15.0, 20.0, 35.0, 50.1 μg/ml with metabolic activation - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- other: MMC (unactivated cultures) and CP (metabolic activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in suspension
DURATION
- Exposure duration: 22.5 hrs (w/o activation); 2 hrs (w/ activation)
- Expression time (cells in growth medium): After 23 hour incubation with Brdu), metaphase cells were collected by mitotic shake off
Positive Controls: mitomycin C (MMC, unactivated cultures) and cyclophosphamide (CP, metabolic activation) - Evaluation criteria:
- Total sister chromatid exchange (SCE), SCE per chromosome, SCE per cell in the M2 stage of mitosis, percentage of cells in the M1, M1+, or M2 stages of cell cycle.
- Statistics:
- Evaluation of mutagenic responses was based on statistical comparisons of SCE frequencies in the C9 treated cultures with those in the negative (solvent) control cultures (Bancroft 1957, Hollander and Wolfe 1973).
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- cytotoxic at 90.2 ug/mL with metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- There were no increases in SCE at any concentration level tested in either the presence or absence of metabolic activation. Cell-cycle delay was not observed at concentration levels below 66.7 ug/mL (w/o activation) or below 50.1 ug/mL (w/ activation). The positive controls produced significant increases in the % SCE as compared to their respective negative controls.
- Conclusions:
- Interpretation of results: negative
The test material did not cause sister chromatid exchange in CHO cells, however it is cytotoxic at the highest concentrations tested.
Referenceopen allclose all
Dose | Cells | # Aberrations | % Cells with | % Cells with > 1 | |
ug/mL | Scored | Per Cell | Aberrations | Aberrations | |
Assay #1: w/o metabolic activation | |||||
Negative Solvent Control | 200 | 0.03 | 2.5 | 0 | |
Positive Control: MMC | 1 | 25 | 0.32 | 24 | 8 |
C9 Aromatics | 45 | 200 | 0.02 | 2 | 0 |
60 | 200 | 0.01 | 0.5 | 0 | |
75 | 200 | 0 | 0 | 0 | |
90 | 200 | 0.01 | 1 | 0 | |
Assay #2: w/o metabolic activation | |||||
Negative Solvent Control | 200 | 0.01 | 0.5 | 0 | |
Positive Control: MMC | 1 | 25 | 0.32 | 24 | 8 |
C9 Aromatics | 15 | 200 | 0.02 | 1 | 0.5 |
30.1 | 200 | 0.04 | 2 | 0.5 | |
60.1 | 200 | 0.02 | 1.5 | 0 | |
90.2 | 200 | Toxic | - | - | |
Dose | Cells | # Aberrations | % Cells with | % Cells with > 1 | |
ug/mL | Scored | Per Cell | Aberrations | Aberrations | |
Assay #1: w/ metabolic activation | |||||
Negative Solvent Control | 200 | 0.03 | 2.5 | 0 | |
Positive Control: CP | 50 | 25 | 0.28 | 24 | 8 |
C9 Aromatics | 25 | 200 | 0.03 | 2 | 0 |
37.5 | 200 | 0.02 | 0.5 | 0 | |
50 | 200 | 0.01 | 0 | 0 | |
70 | 200 | 0.01 | 1 | 0 | |
Assay #2: w/ metabolic activation | |||||
Negative Solvent Control | 50 | 200 | 0.03 | 0.5 | 0 |
Positive Control: CP | 20 | 25 | 0.28 | 24 | 8 |
C9 Aromatics | 40.1 | 200 | 0.01 | 1 | 0.5 |
60.1 | 200 | 0.02 | 2 | 0.5 | |
80.2 | 200 | 0 | 1.5 | 0 | |
100 | 200 | Toxic | - | - |
CHO/HGPRT Forward Mutation Suspension Assay without Metabolic Activation
|
Mean Colony Number |
Relative Population Growth (%) |
Mutant Frequency in 10-6 units |
DMSO |
202.7 ± 7.6 |
111.0 |
1.0 |
DMSO |
190.0 ±17.8 |
89.0 |
2.2 |
5-bromo-2-deoxyuridine |
161.3 ±11.2 |
114.1 |
14.0 |
Methyl methanesulfonate 15 µl/ml |
83.0 ±7.0 |
63.5 |
59.2 |
Methyl methanesulfonate 20 µl/ml |
41.0 ±7.2 |
38.3 |
59.4 |
0.01 µl/ml |
185.0 ±10.6 |
176.6 |
1.1 |
0.02 µl/ml |
204.7± 1.5 |
148.6 |
0.0 |
0.04 µl/ml |
204.3 ±2.5 |
147.5 |
1.9 |
0.06 µl/ml |
202.7± 20.5 |
107.5 |
0.6 |
0.07 µl/ml |
77.3 ±7.0 |
35.2 |
1.4 |
0.08 µl/ml |
5.7 ±1.5 |
10.7 |
0.9 |
0.1 µl/ml |
0.0± 0.0 |
ND |
ND |
0.13 µl/ml |
0.0 ±0.0 |
ND |
ND |
CHO/HGPRT Forward Mutation Suspension Assay with Metabolic Activation
|
Mean Colony Number |
Relative Population Growth (%) |
Mutant Frequency in 10-6 units |
DMSO |
203.7 ± 16.9 |
90.5 |
0.9 |
DMSO |
201.0 ± 12.5 |
109.5 |
4.4 |
3-methylcholanthene |
201.0 ± 7.8 |
77.1 |
161.3 |
0.02 µl/ml |
185.3 ± 3.5 |
119.7 |
2.6 |
0.04 µl/ml |
205.3 ± 21.1 |
111.7 |
3.4 |
0.06 µl/ml |
196.7 ± 22.0 |
110.0 |
3.4 |
0.07 µl/ml |
3.3 ± 1.5 |
4.0 |
1.3 |
0.08 µl/ml |
0.0 ± 0.0 |
ND |
ND |
0.1 µl/ml |
0.0 ± 0.0 |
ND |
ND |
0.13 µl/ml |
0.0 ± 0.0 |
ND |
ND |
0.16 µl/ml |
0.0 ± 0.0 |
ND |
ND |
0.2 µl/ml |
0.0 ± 0.0 |
ND |
ND |
Dose | Cells | # Chromosomes | # SCE | SCE | SCE/Cell | |
ug/mL | Scored | Chromosomes | (Mean +/- SE) | |||
Assay #1: w/o metabolic activation | ||||||
Negative Control | - | 50 | 1044 | 443 | 0.42 | 8.86 (.36) |
Solvent Control | 11 | 50 | 1038 | 536 | 0.52 | 10.72 (.45) |
Positive Control: MMC | 0.005 | 20 | 420 | 570 | 1.36 | 28.5 (1.13) |
C9 Aromatics | 2 | 50 | 1037 | 530 | 0.51 | 10.6 (.43) |
6.67 | 50 | 1038 | 474 | 0.46 | 9.48 (.51) | |
20 | 50 | 1044 | 480 | 0.46 | 9.6 (.44) | |
66.67 | 50 | 1038 | 524 | 0.5 | 10.48 (.39) | |
200 | Toxic | - | - | - | - | |
Assay #2: w/o metabolic activation | ||||||
Negative Control | - | 50 | 1038 | 399 | 0.38 | 7.98 (.38) |
Solvent Control | 11 | 50 | 1047 | 432 | 0.41 | 8.64 (.5) |
Positive Control: MMC | 0.005 | 20 | 417 | 547 | 1.31 | 27.35 (1.49) |
C9 Aromatics | 35 | 50 | 1043 | 428 | 0.41 | 8.56 (.49) |
50.1 | 50 | 1042 | 461 | 0.44 | 9.22 (.36) | |
66.7 | 50 | 1041 | 443 | 0.43 | 8.86 (.44) | |
90.1 | 50 | Toxic | - | - | - | |
Dose | Cells | # Chromosomes | # SCE | SCE | SCE/Cell | |
ug/mL | Scored | Chromosomes | (Mean +/- SE) | |||
Assay #1: w/ metabolic activation | ||||||
Negative Control | - | 50 | 1037 | 443 | 0.43 | 8.86 (.43) |
Solvent Control | 11 | 50 | 1032 | 430 | 0.42 | 8.60 (.49) |
Positive Control: MMC | 1.5 | 20 | 415 | 379 | 0.91 | 18.95 (1.20) |
C9 Aromatics | 0.667 | 50 | 1038 | 449 | 0.43 | 8.98 (.34) |
2 | 50 | 1034 | 484 | 0.47 | 9.68 (.43) | |
6.67 | 50 | 1045 | 474 | 0.45 | 9.48 (.46) | |
20 | 50 | 1040 | 441 | 0.42 | 8.82 (.45) | |
66.67 | 50 | Toxic | - | - | - | |
Assay #2: w/ metabolic activation | ||||||
Negative Control | - | 50 | 1048 | 417 | 0.4 | 8.34 (.43) |
Solvent Control | 11 | 50 | 1046 | 398 | 0.38 | 7.96 (.38) |
Positive Control: MMC | 1.5 | 20 | 418 | 457 | 1.09 | 22.85 (.91) |
C9 Aromatics | 15 | 50 | 1043 | 372 | 0.36 | 7.44 (.40) |
20 | 50 | 1048 | 444 | 0.42 | 8.88 (0.44) | |
35 | 50 | 1055 | 400 | 0.38 | 8.00 (.46) | |
50.1 | 50 | 1047 | 420 | 0.4 | 8.4 (.48) | |
66.7 | 50 | Toxic | - | - | - |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Genetic Toxicity in vivo - Micronucleus
Assay in Mouse Bone Marrow (OECD TG 474)
Genetic Toxicity in vivo - Mammalian Bone Marrow Chromosome Aberration
Test (OECD TG 475) - Read-Across from C9 Aromatics
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:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to OECD Guideline 474. GLP
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Source: Charles River Breeding Laboratories, Inc.
Sex: Male (65), Female (65)
Age at study initiation: Approximately 9-10 weeks
Weight at study initiation: 23-39g
Housing: Individually
Diet (e.g. ad libitum): Purina Certified Rodent 5002 chow (pellets), ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 35d
ENVIRONMENTAL CONDITIONS
Temperature (°F): 68-76
Humidity (%): 40-70%
Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- Corn oil was used. Dose volume did not exceed 1.0 ml/100 g bw.
- Details on exposure:
- The test material and the carrier were administered by oral gavage as a single dose. The carrier was dosed at a volume equal to the test material dose volume. The individual animal dose volumes did not exceed 1.0 ml/100 g body weight; animals were administered 0.25, 0.5, or 1.0 g test material/ kg body weight. The positive control, cyclophosphamide was administered as a single intraperitoneal injection (40 mg/kg) using water as a carrier.
- Duration of treatment / exposure:
- Animals were sacrificed 24, 48 and 72 hours after dose administration.
- Frequency of treatment:
- One dose was given at either 0.25, 0.5 or 1.0 g test material/ kg body weight.
- Post exposure period:
- Animals were sacrificed 24, 48 and 72 hours after dose administration.
- Remarks:
- Doses / Concentrations:
0.25, 0.5, 1.0g/kg/bw
Basis:
other: oral gavage - No. of animals per sex per dose:
- Male (65), Female (65) ; 5 Males and 5 Females per treatment group
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- The positive control, cyclophosphamide was administered as a single intraperitoneal injection (40 mg/kg) using water as a carrier.
- Tissues and cell types examined:
- Erythrocytes derived from femur bone marrow.
- Details of tissue and slide preparation:
- Immediately following the sacrifice of the animals, both femurs were removed and the bone marrow was removed and suspended in fetal bovine serum. After the suspension was centrifuged the pellet was resuspended and smears were prepared (two slides per animal).
- Evaluation criteria:
- Slides were stained using acridine orange; polychromatic erythrocytes (PCE) stained red/orange, nonchromatic erythrocytes (NCE) are unstained (dull green), and micronuclei stain bright yellow. Additional criteria for scoring micronuclei are a circular appearance and a diameter between 1/20 and 1/5 of the cell’s diameter. 1000 PCE from each animal were examined for the presence of micronuclei and the ratio of PCE to NCE was determined for each animal by counting 1000 erythrocytes (PCE and NCE).
- Statistics:
- Calculation of means and standard deviations of the micronuclei data and a test of equality of group means by a standard one way analysis of variance at each time period (ANOVA). When ANOVA was significant, comparisons of carrier control to dosed group means were made according to Duncan’s Multiple Range Test.
A standard regression analysis was performed to test for a dose response.
Residuals from the ANOVA were analyzed for normality by Wilk’s Criterion. The residuals were normally distributed (values were greater than 0.01 level of significance). Therefore nonparametric analysis was not performed.
Sexes were analyzed separately. - Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- 2(male), 1 (female) animals at 2.5 g/kg; 1 (female) at 1.0 g/kg
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- The positive control (cyclophosphamide) induces a statistically significant increase in the mean number of micronucleated polychromatic erythrocytes, indicating that the positive control was clastogenic and was responding in an appropriate manner. Carrier control values for the mean percent of polychromatic erythrocytes and for the mean number of micronucleated polychromatic erythrocytes are within the normal range for the corn oil control.
MRD-90-884 did not induce a statistically significant increase in the mean number of micronucleated polychromatic erythrocytes. A significant regression coefficient (p<0.05) was observed in the mean micronucleated polychromatic erythrocytes for the 48 hour female group. However, the mean values were not significant when compared to the carrier control and were within the normal range of the carrier control. Therefore this statistical response is not believed to be biologically significant. MRD-90-884 was not clastogenic in mouse bone marrow under the conditions of this test.
Necropsies of the four animals that died prior to the scheduled sacrifice (2(male), 1 (female) animals at 2.5 g/kg; 1 (female) at 1.0 g/kg) revealed that most common effects were urine stains and a tan mucous like material in the small intestine. The most probable cause of death was due to the toxicity of the test material. - Conclusions:
- Interpretation of results: negative
These data indicate that MRD-90-884 is not cytotoxic and is not clastogenic in CD-1 mouse bone marrow cells at doses up to and including 1.0 g/kg of body weight. - Executive summary:
The test material, MRD-90-884 was tested in the mammalian bone marrow micronucleus assay using CD-1 mice. MRD-90-884 was tested at 24, 48, and 72 hour intervals following exposure and did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes or an increase in the mean number of micronucleated polychromatic erythrocytes. Both the positive (cyclophosphamide) and the negative (carrier) controls behaved in an appropriate manner. These data indicate that MRD-90-884 is not cytotoxic and is not clastogenic in CD-1 mouse bone marrow cells at doses up to and including 1.0 g/kg.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Source of data is from secondary literature. Acceptable well-documented study report which meets basic scientific principles: GLP.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- chromosome aberration assay
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of administration:
- inhalation: vapour
- Details on exposure:
- - Exposure apparatus: 16 m glass and steel chambers.
- Method of holding animals in test chamber: cages
- Source and rate of air: Air was provided by a seperate HVAC system.
- Method of conditioning air: Air was filtered for particulates and temperature and humidity controlled.
- System of generating particulates/aerosols: Test atmosphere was generated by heating nitrogen to 200 degree C by passing it through a 1 L stainless steel cylinder with a 1500 W band heater. The nitrogen then passed through a glass column 7.6 cm diameter and 30 cm long packed with glass beads. Test material was delivered by a metering pump into Teflon tubing, to the bottom of the column. The liquid test substance vaporized as it went up the column with the nitrogen. The vapor then went into the test chambers where dilution with the chamber ventilation air produced the desired concentrations.- Temperature, humidity, pressure in air chamber: Air flow rate, temperature and relative humidity were monitored every half-hour during exposure.
TEST ATMOSPHERE
- Brief description of analytical method used: Measurements made hourly using gas-phase IR.
- Samples taken from breathing zone: yes - Duration of treatment / exposure:
- 6 hours/day
- Frequency of treatment:
- 5 days
- Post exposure period:
- 6, 24, or 48 hours
- Remarks:
- Doses / Concentrations:
0, 150, 500, 1500 ppm
Basis:
nominal conc. - Remarks:
- Doses / Concentrations:
0, 153 (9.6), 471 (13.1), 1540 (48) ppm
Basis:
analytical conc. - No. of animals per sex per dose:
- 15 male/15 female
- Control animals:
- yes, concurrent no treatment
- Positive control(s):
- 10 animals of each sex were exposed to cyclophosphamide
- Route of administration: injected intraperitoneally
- Doses / concentrations: 40 mg/kg - Tissues and cell types examined:
- bone marrow
- Details of tissue and slide preparation:
- DETAILS OF SLIDE PREPARATION: 4 slides per rat were stained with Giemsa.
METHOD OF ANALYSIS: Slides were scanned for well resolved metaphase spreads. Fifty metaphases per animal were evaluated. - Evaluation criteria:
- total number of chromosome aberrations, frequency of aberrations per metaphase, percent metaphases with one or more aberrations, percent metaphases with two or more aberrations
- Statistics:
- Kruskal-Wallis multiple group comparison test followed by the Mann-Whitney U test
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- reduced body weight gain in 1500 ppm group
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results: negative
The test substance was not clastogenic at levels up to and including 1500 ppm. - Executive summary:
The test substance was not clastogenic at levels up to and including 1500 ppm.
Referenceopen allclose all
Chromosome Aberrations in Sprague-Dawley Rats
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
C10-C15 Aromatics are not mutagenic using in vitro or in vivo genotoxicity assays. Further data derived from read across data from the supporting substance (structural analogue or surrogate), the C9 Aromatics also support the conclusion that C10-C15 Aromatics are not genotoxic. In bacterial reverse mutation tests, C10-C15 Aromatics were not mutagenic in the presence or absence of metabolic activation. Likewise, there were no mutagenic effects reported in a read-across in vitro mammalian gene mutation test (HGPRT forward mutation assay) in the supporting substance, C9 Aromatics. No in vitro chromosomal effects were reported in a Chinese hamster ovary assay that examined the C9 Aromatics. The test substance, C10-C15 Aromatics, did not produce chromosomal effects when tested in an in vivo mouse bone marrow micronucleus assay. Likewise, the supporting substance C9 Aromatics, were not clastogenic in an in vivo mammalian bone marrow chromosome aberration test. These data demonstrate that these substances are not categorizable genotoxins either in vitro or in vivo. Furthermore, no there evidence of hyperplastic responses or pre-neoplastic lesions in sub-chronic and chronic repeat-dose studies in either the C9 aromatics or the C10-C15 Aromatics. All studies were conducted in a manner similar or equivalent to currently established OECD guidelines. C10-C15 Aromatics are a non-genotoxic agent and classification is not warranted.
Justification for classification or non-classification
The negative results using in vitro and in vivo genotoxicity assays do not warrant the classification of C10-C15 Aromatics fluids as genotoxins under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.