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EC number: 275-604-2 | CAS number: 71550-24-8
- 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
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- Endpoint summary
- Stability
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- 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 was tested in an Ames test in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102 with and without metabolic activation. The maximum concentration tested was limited by a reduction of bacterial background lawn. In two independent experiments no biologically relevant increase in revertant colony numbers of any of the five tester strains was observed. Therefore the substance is considered non-mutagenic (Eurofins 2017).
In 1995 a very pure batch of the substance was tested in an Ames test with TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 with and without metabolic activation in a plate incorporation assay. In TA100 with metabolic activation a dose related > 2 -fold increase of the number of revertants was reported at non-cytotoxic concentrations. In all other strains and TA100 without metabolic activation no increase was reported (JBC 1995).
An additional Ames test with TA 1535, TA 1537, TA 98 and TA 100 with metabolic activation in a plate incorporation assay was negative in all strains tested (Bayer 1980)
In a HPRT assay according to OECD 476 the substance did not induce mutations in V79 cells both in presence and absence of metabolic activation. The substance was tested up to cytotoxic concentrations.
It can be concluded that the substance is negative in this test and does not induce mutations in mammalian cells (Bayer 2002).
In a chromosome aberration test V79 cells were exposed to the substance for 4 hours (with and without metabolic activation) or 21 hours (without metabolic activation). Three or four concentrations (maximum concentration based on 55± 5% cytotoxicity) per experiment were evaluated for the presence of chromosom aberrations. No increase in the number of aberrations compared to control and/or historical controls was observed. Positive controls were within historical ranges. The substance is considered not clastogenic in this assay (Eurofins 2017).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 31 January 2002 to 27 April 2002
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- July 21, 1997
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- GLP compliance:
- yes
- Type of assay:
- other: HPRT forward mutation in mammalian cells
- Specific details on test material used for the study:
- purified laboratory sample
- Target gene:
- 6-thioguanine
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: University of Ulm, Germany
- Cell cycle length, doubling time or proliferation index: 10-14 hours
- Methods for maintenance in cell culture: stock kept under liquid nitrogen
- Modal number of chromosomes: 22
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: maintained in plastic vessels at 37 °C and 5%CO2, recloned by subculturing twice weekly (checked regularly for karyotype and mycoplasma presence)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability:yes - Metabolic activation:
- with and without
- Metabolic activation system:
- S9 derived from Aroclor 1254 induced rat liver homogenate (concentration in test medium 5%)
- Test concentrations with justification for top dose:
- exp 1 without metabolic activation: 10, 20, 40, 60, 80 and 100 µg/mL
exp 2 without metabolic activation: 15, 30, 60, 90, 120 and 240 µg/mL
exp 1 with metabolic activation: 60, 80, 100, 120, 160, 200 and 240 µg/mL
exp 2 with metabolic activation: 60, 80, 100, 120, 160, 200 and 240 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: deionized water
- Justification for choice of solvent/vehicle: substance soluble up to 250 mg/mL in pre-test (precipitate in culture medium at 240 µg/mL and above) - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- other: dimethylbenzanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Exponentially growing cells were plated in culture medium in 250 mL flasks for 16-24 hours to allow attachment. Thereafter the cells were exposed for 5 hours. Monolayers were washed with PBS, trypsinized and replated in 20 mL culture medium (1.5E06 cells/250 mL) in flasks and in 3 petri dishes (5 mL medium with 200 cells/dish).
Petri dishes were incubated for 6 days and used to assess cytotoxicity (survival to treatment).
The cells in the flasks were incubated to permit growth and expression of mutations. After 6 days the cells were re-seeded in 8 petri dishes per culture at 3E05 cells/dish in presence of 6-thioguaninine. Three additional petri dishes with 200 cels/dish were used to calculate cloning efficiency.
After 6-8 days of incubation colonies were fixed, stained with Chiemsa and counted.
NUMBER OF REPLICATIONS: 8/concentration
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency and relative total growth - Evaluation criteria:
- 1) assessment in at least 5 replicates per concentration with relative survival, relative population growth and absolute cloning efficiency > 10%
2) positive result with dose related increase in mutant frequency (at least 2-3 times of vehicle controls) and this finding can be reproduced in a separate experiment
3) no unphysiological culture conditions (effects on pH and osmolality)
4) scientific judgement - Statistics:
- ANOVA and Dunnet test
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- maximum concentrations based on cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none
- Effects of osmolality: none
- Evaporation from medium: NA
- Precipitation: at and above 240 µg/mL
RANGE-FINDING/SCREENING STUDIES:without metabolic activation: 100% cell death at 100 µg/mL; with metabolic activation 100% cell death at 240 µg/mL
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: included in the report
- Negative (solvent/vehicle) historical control data: included in the report
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- cloning efficiency, rel growth: no effects up to 240 µg/mL:
- survival to treatment: in all experiments with and without metabolic activation cell death (100%) at 240 µg/mL - Conclusions:
- The substance did not induce mutations in mammalian cells
- Executive summary:
In a HPRT assay according to OECD 476 the substance did not induce mutations in V79 cells both in presence and absence of metabolic activation. The substance was tested up to cytotoxic concentrations.
It can be concluded that the substance is negative in this test and does not induce mutations in mammalian cells.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: TA 98, TA 1535 and TA 102 MOLTOX, INC., NC 28607, USA; TA 100 and TA 1537 Xenometrix AG, Switzerland.
- Methods for maintenance in cell culture if applicable: stock cultures stored with nutrient broth (OXOID) supplemented with DMSO (approx. 8% v/v) over liquid nitrogen - Metabolic activation:
- with and without
- Metabolic activation system:
- liver microsomal fraction from rats treated with phenobarbital / β-naphthoflavone
- Test concentrations with justification for top dose:
- exp 1: 0.00316, 0.0100, 0.0316, 0.100, 0.316, 1.0 and 2.5 µL/plate (TA 98 and TA 100)
in addition for TA 1535, TA 1537 and TA 102: 0.00100 µL/plate
exp 2: 0.000316, 0.00100, 0.00316, 0.0100, 0.0316, 0.100, 0.316 and 1.0 µL/plate
Top doses limited by reduction of bacterial background lawn (without S9 at and above 0.1-1 ug/plate; with S9 at and above 0.1-2.5 ug/plate). - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: destilled water
- Justification for choice of solvent/vehicle: solubility - Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- methylmethanesulfonate
- other: 4-nitro-o-phenylene-diamine; 2-aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: exp 1 plate incorporation; exp 2 preincubation
DURATION
- Preincubation period: 60 min at at 37 °C
- Incubation time: at 37 °C for at least 48 h in the dark
NUMBER OF REPLICATIONS: 3/concentration
DETERMINATION OF CYTOTOXICITY
- Method: reduction of bacterial background lawn - Evaluation criteria:
- A test item is considered as mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs
in at least one tester strain with or without metabolic activation.
A biologically relevant increase is described as follows:
- if in tester strains TA 98, TA 100 and TA 102 the number of reversions is at least twice as high
- if in tester strains TA 1535 and TA 1537 the number of reversions is at least three times higher
than the reversion rate of the solvent control - Statistics:
- NA
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 0.316 - 2.5 µL/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 0.1-1.0 ug/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 0.1-1.0 ug/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 0.1-1.0 ug/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 0.316-1.0 ug/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- The substance is considered non-mutagenic under the conditions of the test.
- Executive summary:
The substance was tested in an Ames test in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102 with and without metabolic activation. The maximum concentration tested was limited by a reduction of bacterial background lawn. In two independent experiments no biologically relevant increase in revertant colony numbers of any of the five tester strains was observed. Therefore the substance is considered non-mutagenic.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 03 February 2017 to 24 April 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- 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 (incl. QA statement)
- Type of assay:
- other: in vitro chromosome aberration test in mammalian cells
- Target gene:
- NA
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Eurofins Munich (ATCC, CCL-93)
- Cell cycle length: 12-14 hours
- Methods for maintenance in cell culture: stored under liquid nitrogen if applicable:
- Modal number of chromosomes: 2n=22
MEDIA USED
- Type and identity of media including CO2 concentration: MEM (minimum essential medium) supplemented with 10% FBS (fetal bovine serum) (5% CO2)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes - Additional strain / cell type characteristics:
- not applicable
- Cytokinesis block (if used):
- colcemid 17.5 hours after treatment
- Metabolic activation:
- with and without
- Metabolic activation system:
- The S9 liver microsomal fraction was prepared from phenobarbital/β-naphthoflavone induced rat liver homogenate
- Test concentrations with justification for top dose:
- exp 1 (4 h without metabolic activation): 25, 50, 75, 100, 125, 150, 175, 200 and 250 µg/mL (evaluated 25, 50, 75 and 100 µg/mL)
exp 1 (4 h with metabolic activation): 200, 250, 300, 325, 350, 375, 400, 425, 450 and 500(P) µg/mL (evaluated 250, 325 and 375 µg/mL)
exp 2 (21 h without metabolic activation): 25, 50, 75, 100, 125, 150, 175, 200 and 250 µg/mL (evaluated 50, 125 and 250 µg/mL - Vehicle / solvent:
- Exp 1: MEM (minimum essential medium)
Exp 2: MEM (minimum essential medium) supplemented with 10% FBS
pH was adapted to 7 ± 0.4 with sodium hydroxide solution. For osmolality 354 mOsmol/kg was measured at 5 mg/mL - Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in suspension
- Cell density at seeding: 1E04 cells/mL
DURATION
- Exposure duration: 4 hours (with and without metabolic activation) and 21 hours (without metabolic activation)
- Expression time (cells in growth medium): 17 h (4 hours experiments)
- Selection time (if incubation with a selection agent): colcemid 17.5 hours after start of treatment
- Fixation time (start of exposure up to fixation or harvest of cells): 21 hours after start of treatment
SPINDLE INHIBITOR (cytogenetic assays): colcemid
NUMBER OF REPLICATIONS: 2/concentration
PREPARATION: After ca 20 hours preparation was started. At first cells were trypsinated and resuspended in about 9 mL complete culture medium. An aliquot of each culture was removed to determine the cell count by a cell counter (AL-Systems).Then cultures were transferred into tubes and incubated with hypotonic solution (0.4% KCl) for 15-20 min. After hypotonic treatment the cells were fixed at least two times with 3 + 1 methanol + glacial acetic acid and spread onto the slides. After the fixation steps the slides were dried and stained with Giemsa. The slides were coverslipped using 2-3 drops of Eukitt(R). Afterwards they were air dried. 300 well-spread metaphases were microscopically analysed for cytogenetic damage
DETERMINATION OF CYTOTOXICITY
- Method: releative increase in cell count (RICC)
OTHER EXAMINATIONS:
- Determination of polyploidy: included - Rationale for test conditions:
- based on pre-test at 5, 10, 25, 50, 100, 250, 500, 1000, 2500 and 5000 µg/mL (4 h with and without metabolic activation)
- Evaluation criteria:
- positive:
a) at least one of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
b) the increase is dose-related when evaluated with an appropriate trend test,
c) any of the results are outside the distribution of the historical negative control data
negative:
a) none of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
b) there is no concentration-related increase when evaluated with an appropriate trend test,
c) all results are inside the distribution of the historical negative control data. - Statistics:
- Fisher´s exact test; Chi-square Test
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at and above 100 µg/mL (4 hours without metabolic activation) at and above 400 µg/mL (4 hours with metabolic activation) at and above 250 µg/mL (21 hours without metabolic activation)
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS: none
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%): available in the report
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: RICC
RICC compared to controls :
exp 1 without metabolic activation: 59% at 75 µg/mL, 34% at 100 µg/mL, 11% at 125 µg/mL and 0% and below at 150 µg/mL and higher
exp 1 with metabolic activation: 66% at 325 µg/mL, 49% at 350 µg/mL, 43% at 375 µg/mL, 22% at 400 µg/mL, 7% at 425 µg/mL and 0% and below at 450 µg/mL and higher
exp 2: without metabolic activation: 69% at 75 µg/mL, 54% at 100 µg/mL, 62% at 125 µg/mL, 56% at 150 µg/mL, 48% at 175 µg/mL, 50% at 200 µg/mL and 41% at 250 µg/mL - Conclusions:
- The substance did not induce aberrations in V79 cells. The substance is considered not clastogenic in this assay.
- Executive summary:
In a chromosome aberration test V79 cells were exposed to the substance for 4 hours (with and without metabolic activation) or 21 hours (without metabolic activation). Three or four concentrations (maximum concentration based on 55 ± 5% cytotoxicity) per experiment were evaluated for the presence of chromosome aberrations. No increase in the number of aberrations compared to control and/or historical controls was observed. Positive controls were within historical ranges. The substance is considered not clastogenic in this assay.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- August 24 1995 to September 7 1995
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- plated in duplicate
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- JMIT
- Principles of method if other than guideline:
- The use of duplicate plating was not justified
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine (Salmonella typhimurium) or tryptophan (E coli)
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: slamonella typhimurium from Bruce Ames, California University, E coli from Institute of medical Science, University of Tokyo - Metabolic activation:
- with and without
- Metabolic activation system:
- S9 prepared from liver homogenate of rats treated with phenobarbital/5,6-benzoflavone
- Test concentrations with justification for top dose:
- exp 1 : 10, 50, 100, 500, 1000 and 5000 ug/plate (S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 with and without S9)
exp 2: 5, 10, 20, 39, 78 and 156 ug/plate (TA 1535 and TA 100 without S9); 10, 20, 39, 78, 156 and 313 ug/plate ( TA 1537 and TA 98 without S9); 39, 78, 156, 313, 625 and 1250 ug/plate (E. Coli without S9) ;
20, 39, 78, 156, 313 and 625 ug/plate (TA 1535 and TA 100 with S9); 39, 78, 156, 313, 625 and 1250 ug/plate ( TA 1537 and TA 98 with S9); 156, 313, 625, 1250, 2500 and 5000 ug/plate (E. Coli with S9)
exp 3: 5, 10, 20, 39, 78 and 156 ug/plate (TA 1535 and TA 100 without S9); 20, 39, 78, 156 313 and 625 ug/plate ( TA 1537 and TA 98 without S9); 20, 39, 78, 156 313 and 625 ug/plate (TA 1535 and TA 100 with S9): - Vehicle / solvent:
- DMSO
- Justification for choice of solvent/vehicle: stability of substance in vehicle - Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- benzo(a)pyrene
- furylfuramide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Preincubation period: NA
- Exposure duration:48 h at 37 °C
NUMBER OF REPLICATIONS: 2/concentration
DETERMINATION OF CYTOTOXICITY
- Method: not indicated - Evaluation criteria:
- A test item is considered as mutagenic if:
- a significant and dose-related increase in the number of revertants occurs and the number of revertant colonies is at least twice as high with sufficient reproducibility - Statistics:
- NA
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 313 ug/plate and above
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 100 ug/plate and above
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- other: TA 1535, TA 1537, TA 98 and E. coli WP2
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- see doses selected
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: dose related > twofold increase
- Conclusions:
- Under the conditions of the test the substance is considered mutagenic
- Executive summary:
The substance was tested in an Ames test with TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 with and without metabolic activation in a plate incorporation assay. In TA100 with metabolic activation a dose related > 2 -fold increase of the number of revertants was reported at non-cytotoxic concentrations. In all other strains and TA100 without metabolic activation no increase was reported.
Based on this effect the substance has to be considered mutagenic to bacteria.
Referenceopen allclose all
Experiment I,without metabolic activation
Negative Control versus Test Group |
Concentration |
Treatment Time [h] |
Aberrant Cells (excl. gap) |
Significance |
p Value |
1 |
25 |
4 |
11 |
- |
0.6422 |
2 |
50 |
4 |
9 |
- |
1.0000 |
3 |
75 |
4 |
11 |
- |
0.6422 |
4 |
100 |
4 |
7 |
- |
1.0000 |
EMS |
900 |
4 |
20 |
+ |
0.0315 |
Experiment I,with metabolic activation
Negative Control versus Test Group |
Concentration |
Treatment Time [h] |
Aberrant Cells (excl. gap) |
Significance |
p Value |
2 |
250 |
4 |
11 |
- |
0.8208 |
4 |
325 |
4 |
2 |
- |
0.0630 |
6 |
375 |
4 |
9 |
- |
1.0000 |
CPA |
1.11 |
4 |
21 |
+ |
0.0377 |
Experiment II,without metabolic activation
NegativeControl versus Test Group |
Concentration |
Treatment Time [h] |
Aberrant Cells (excl. gap) |
Significance |
p Value |
2 |
50 |
21 |
8 |
- |
0.2222 |
5 |
125 |
21 |
10 |
- |
0.0888 |
9 |
250 |
21 |
8 |
- |
0.2222 |
EMS |
400 |
21 |
24 |
+ |
<0.0001 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
The results of the two Ames tests (Eurofins 2018 and Bayer 1980) are conflicting with one of the tests (JBC 1995) showing a positive result in one strain of Salmonella, TA100 with metabolic activation. As two Ames tests are available with negative results in this strain of Salmonella and all other strains tested are without any effects in all 3 tests, it can be concluded in a weight of evidence approach that the substance is negative in the Ames test.
Justification for classification or non-classification
Based on the information available the substance does not need to be classified for mutagenicity according toRegulation (EC) No 1907/2006.
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