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EC number: 701-459-6 | 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 test substance was found as non-mutagenic in three in vitro studies:
- Gene mutagenicity in bacteria Ames test (S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 and E. coli WP2 uvrA), with or without metabolic activation: negative (OECD 471, BASF, 1995).
- Gene mutagenicity in mammalian cells Mouse lymphoma assay, L5178Y cells, with or without metabolic activation: negative (OECD 476; CHV, 1996)
- Cytogenicity in mammalian cells Chromosome aberration, CHL cells, with or without metabolic activation: negative (OECD 473; BASF 2002).
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2000
- 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)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- - Batch No.: 4879
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver induced with phenobarbital and 5,6-benzoflavone.
- Test concentrations with justification for top dose:
- short-term treatment (-S9 mix): 4.88, 9.77, 19.5, 39.1, 78.1 µg/mL;
short-term treatment (+S9 mix): 19.5, 39.1, 78.1, 156, 313, 625, 1250 µg/mL;
continuous treatment (-S9 mix): 4.88, 9.77, 19.5, 39.1, 78.1 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: Mitomycin C; +S9: Cyclophosphamide
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
NUMBER OF CELLS EVALUATED: 200 - Evaluation criteria:
- The results were judged to be: negative in the case where the appearance frequency of abnormal cells was less than 5 %; equivocal in the case where the frequency was 5 % or more and less than 10 % and also the reproducibility was observed; and positive in the case where the frequency was 10 % or more and also the reproducibility or the dependency on the test substance dose was observed.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cytotoxicity was observed at more than 39.1, 78.1, and 19.5 µg/mL in -S9 mix, +S9 mix and continuous treatments, respectively.
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- Clive et al., 1987, Mutation Research, 189, 143-156
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- thymidine kinase (TK)
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: culture medium: RPMI 1640 supplemented with Pluronic® F68, L-glutamine, sodium pyruvate, antibiotics and 10% horse serum; treatment medium: Fischer's medium with same supplements but 5% horse serum; cloning medium: same culture medium but with 20% horse serum and without Pluronic® F68 and addition of BBL purified agar (0.24%); selection medium: cloning medium containing 3 µg/ml of TFT (5-trifluorothymidine)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced rat liver
- Test concentrations with justification for top dose:
- 3.13, 6.25, 12.5, 25, 50, 100 µg/mL
- Vehicle / solvent:
- - Vehicle used: DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 h
- Expression time (cells in growth medium): 2 h
- Selection time (if incubation with a selection agent): 10-14 h
SELECTION AGENT: 5-trifluorothymidine (TIFT)
NUMBER OF REPLICATIONS: 2 independent trials, 3 vehicle controls, 2 positive controls in each trial
NUMBER OF CELLS EVALUATED: approx. 3*10e5 - Evaluation criteria:
- - The minimum criterion considered necessary to demonstrate mutagenesis for any given treatment is a mutant frequency that is ≥ 2 times the concurrent background mutant frequency (as the average of the vehicle control cultures).
- A dose-related or toxicity-related increase in mutant frequency should be observed.
- If the mutant frequency obtained for a single dose at or near the highest testable toxicity is about two or more times the minimum criterion, the test substance will be considered mutagenic in a single trial.
- Treatments that induce less than ten percent relative growth are included in the assay, but are not used as primary evidence for mutagenicity. - Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: above 100 mg/L
RANGE-FINDING/SCREENING STUDIES: In preliminary range finding tests no cytotoxicity at 1000 µg/mL was observed. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- purity unknown, no second independent trial
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- No second independent trial was performed.
- Principles of method if other than guideline:
- Ames et al. (1975)/ Maron and Ames (1983)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his-
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced rat liver
- Test concentrations with justification for top dose:
- 100, 250, 500, 1000, 2500, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Remarks:
- sterility control
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9 mix : 2-nitrofluorene (TA98, TA1538), sodium azide (TA1535, TA100), ICR-191 (TA1537 ); +S9 mix : 2-Aminoanthracene (five strains)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 ± 8 hours
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- TA98 and TA100 considered positive if the TS produced at least a 2-fold increase in revertants per plate over vehicle control and a dose response to increasing concentrations; same criteria for the other strains but 3-fold increase.
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative 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:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative 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:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative 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:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
Referenceopen allclose all
Trial 1 was not considered acceptable because of cell culture problems (slower growth; positive control cultures were excessively cytotoxic; the vehicle control mutant frequencies, while still in the acceptable range, were higher than usual). However, no mutagenicity of the test substance was observed.
Trial 2 |
|||||
Treatment (µg/mL) |
Metabolic activation |
Suspension growth *a |
Cloning efficiency *b |
Relative growth *c |
Mutant frequency (10e-6units)*d |
3.13 |
no |
109 |
85 |
93 |
92 |
|
yes |
110 |
80 |
88 |
108 |
6.25 |
no |
102 |
77 |
79 |
115 |
|
yes |
105 |
76 |
80 |
81 |
12.5 |
no |
104 |
75 |
78 |
111 |
|
yes |
105 |
89 |
93 |
84 |
25 |
no |
86 |
79 |
68 |
105 |
|
yes |
86 |
92 |
79 |
91 |
50 |
no |
92 |
87 |
79 |
97 |
|
yes |
89 |
85 |
76 |
110 |
100 |
no |
82 |
73 |
60 |
100 |
|
yes |
67 |
90 |
61 |
123 |
*a = relative to vehicle control
*b = relative to vehicle control, total viable colony count/ number of cells seeded * 100
*c = (relative suspension growth + relative cloning efficiency)/ 100
*d = relative to vehicle control, (total mutant colonies/ total viable colonies) * 2 * 10e-4; decimal is moved to express the frequency in units for 10e-6
Table 1: Plate Incorporation Test
Strain |
Metabolic activation system |
Replicates |
Maximum revertant factor |
Dose dependency |
Assessment |
TA 98 |
no |
3 |
1.0 |
no |
negative |
yes |
3 |
0.9 |
no |
negative |
|
TA 100 |
no |
3 |
1.2 |
no |
negative |
yes |
3 |
1.0 |
no |
negative |
|
TA 1535 |
no |
3 |
1.2 |
no |
negative |
yes |
3 |
1.1 |
no |
negative |
|
TA 1537 |
no |
3 |
0.9 |
no |
negative |
yes |
3 |
1.1 |
no |
negative |
|
TA 1538 |
no |
3 |
1.4 |
no |
negative |
yes |
3 |
1.0 |
no |
negative |
|
WP2ucrA |
no |
3 |
0.9 |
no |
negative |
yes |
3 |
1.5 |
no |
negative |
Solvent: DMSO
Precipitation occurred in doses of ≥1000 µg/plate
In preliminary dose range-finding studies (TA100, 6.8-5000 µg/plate, 10 doses) no cytotoxicity with and without S9-mix; precipitates at 1000 µg/plate (background lawn could not be evaluated).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Gene mutagenicity in bacteria
For the gene mutagenicity in bacteria, a GLP compliant study is available, which was performed according to OECD guideline 471 (BASF, 1995). The study was performed as plate incorporation tests with S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 and E. coli WP2 uvrA with or without metabolic activation up to 5000 µg/plate. All strains gave negative results. This result is supported by the negative result of another bacterial reverse mutation assay conducted with S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and E. coli strain WP2 uvrA with and without metabolic activation at doses of 2.29 -5000 µg/plate (MHLW, 2001).
Gene mutagenicity in mammalian cells
In an in vitro mammalian cell gene
mutation assay according to OECD guideline 476, L5178Y cells cultured
in vitro were exposed to C.I. Pigment Yellow 53 at concentrations of
3.13, 6.25, 12.5, 25, 50 and 100 µg/mL (suspension with DMSO) in the
presence and absence of mammalian metabolic activation (Aroclor-induce
rat liver (S9)) (BASF, 1996). Higher concentrations were not tested
because of the insoluble nature of the test substance. All dosing
solutions were washed to remove the visible precipitate before
application. Two trials of the non-activation and the S9 metabolic
activation mutation assays were performed but the first trial was
disregarded because of problems in the cell cultures. In Trial 2, six
treatments from 3.13 µg/mL to 100 µg/mL were initiated and all doses
were cloned for mutant analysis. No cytotoxicity was observed under
either activation conditions. None of the six analysed treatments with
or without metabolic activation induced a mutant frequency that
exceeded the minimum criterion for a positive response. Nickel
Antimony Titanate was therefore evaluated as negative with and without
metabolic activation at the TK locus in L5178Y mouse lymphoma cells
under the conditions used in this study.
Cytogenicity in mammalian cells
In a mammalian chromosomal
aberration test according to OECD guideline 473 (MHLW 2002), Chinese
hamster lung cells (CHL/IU) were exposed to the test substance at
concentrations of:
- 9.79, 19.5, 39.1 μg/mL without metabolic activation (short term
treatment, -S9)
- 19.5, 39.1, 78.1 μg/mL with metabolic activation (short term
treatment,+S9)
- 4.88, 9.75, 19.5 μg/mL without metabolic activation (continuous
treatment, 24 hours)
The S9 mix was composed of phenobarbital- and 5,6-benzoflavone-induced
rat liver. No increase in chromosomal aberrations was observed in the
test with either the short term treatment (-S9 mix and +S9 mix) or the
continuous treatment.
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on the available in vitro data, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the ninth time in Regulation (EC) No 2016/1179.
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