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EC number: 215-199-1 | CAS number: 1312-76-1
- 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
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Remarks:
- RCC-Cytotest Cell Research GmbH
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELL CULTURE DETAILS:
- Type and identity of media: Minimal Essential Medium supplemented with 10% fetal calf serum.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital / ß-Naphthoflavone induced rat liver S9-mix
- Test concentrations with justification for top dose:
- 19.5, 39.1, 78.1 & 156.3 µg active ingredient/mL
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- medium
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 300-400 µg/mL Ethylmethane sulfonate (-S9), 1.4-2.0 µg/mL Cyclophosphamide (+S9)
- Details on test system and experimental conditions:
- - Spindle inhibitor: 0.2 µg/ml Colcemid
- Stain: Giemsa
- No. of metaphases analyzed: 100
- Dosing: Cytotoxic concentrations were determined in a range-finder study with and without metabolic activation. 312.5 µg/ml was chosen as top concentration in the actual experiments.
- Number of replicates: 2 - Evaluation criteria:
- Breaks, fragments, deletions, exchanges, and chromosome disintegrations were recorded as structural chromosome aberrations. Gaps were recorded as well, but not included in the calculation of aberration rates. Only metaphases with characteristic chromosome numbers (22+-1) were included in the analysis. The mitotic index (% cells in mitosis) and the percentage of polyploid cells in 500 metaphase plates/culture were determined.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 156.3 - 312.5 µg active ingredient/mL
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: according to OECD 476
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Guideline:
- other: Japanese Guidelines: Kanpoan No. 287, Environment Protection Agency; Eisei No. 127, Ministry of Health and Welfare; Heisei 09/10/31 Kikyoku No. 2, Ministry of International Trade and Industry
- Principles of method if other than guideline:
- first experiment 4 hours treatment with and without metabolic activation
second experiment 24 hours treatment without metabolic activation and 4 hours treatment with metabolic activation - GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Harlan Cytotest Cell Research GmbH
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- HPRT
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: MEM
- 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:
- Rat liver S9
- Test concentrations with justification for top dose:
- Experiment I:
without S9 mix: 28.1; 56.3; 112.5; 225.0; 337.5; 450 µg/mL
with S9 mix: 56.3; 112.5; 225.0; 450.0; 675.0; 900.0 µg/mL
Experiment II:
without S9 mix: 28.1; 56.3; 112.5; 225.0; 450.0; 675.0 µg/mL
with S9 mix: 112.5; 225.0; 450.0; 900.0; 1350.0; 1800 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: solubility properties - Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- Migrated to IUCLID6: 7,12-dimethylbenz(a)anthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours with and without metabolic activation in experiment 1, 24 hours without metaoblic activation in experiment 2
- Expression time (cells in growth medium): 72 hours
- Selection time (if incubation with a selection agent): 10 days
SELECTION AGENT (mutation assays): Thioguanine
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: >1,5x10exp.6
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
- Evaluation criteria:
- A test item is classified as positive if it induces either a concentration-related increase of the mutant frequency or a reproducible and positive response at one of the test points.
A test item producing neither a concentration- related increase of the mutant frequency nor a reproducible positive response at any of the test points is considered non-mutagenic in this system.
A positive response is described as follows:
A test item is classified as mutagenic if it reproducibly induces a mutation frequency that is three times above the spontaneous mutation fre¬quency at least at one of the concentrations in the experiment.
The test item is classified as mutagenic if there is a reproducible concentration-related increase of the mutation frequency. Such evaluation may be considered also in the case that a threefold increase of the mutant frequency is not observed.
However, in a case by case evaluation this decision depends on the level of the corre-sponding negative control data. If there is by chance a low spontaneous mutation rate in the range normally found (0.5 – 31.8 mutants per 10exp.6 cells) a concentration-related in-crease of the mutations within this range has to be discussed. The variability of the mutation rates of negative and solvent controls within all experiments of this study was also taken into consideration. - Statistics:
- Linear regression analysis (least squares) .
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, C-SAT 080094 is considered to be non-mutagenic in this HPRT assay. - Executive summary:
The study was performed to investigate the potential of C-SAT 080094 to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster.
The assay was performed in three independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The experimental part without metabolic activation was terminated prematurely due to exceedingly severe cytotoxic effects even al low concentrations. This part of the first experiment was repeated in experiment IA using a lower concentration range. The data of the repeat experiment IA are included in the first experiment.
The second experiment was performed in the absence of metabolic activation with a treatment period of 24 hours and in the presence of metabolic activation with a treatment period of 4 hours.
The highest applied concentration in the pre-test on toxicity (7300 µg/mL) was based on the purity of the test item (36 % active ingredient). The dose range of the main experiments was limited by toxicity of the test item.
No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments.
Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.
- 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:
- other: see 'Remark'
- Remarks:
- GLP - Guideline study, tested with the source substance disodium metasilicate nonahydrate. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
- 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:
- his operon (for S. tyhphimurium strains)
trp operon (for E. coli strain) - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor-induced rat liver S-9 mix and uninduced hamster liver S-9 mix
- Test concentrations with justification for top dose:
- standard plate test: 33, 100, 333, 1000, 2500, 5000 µg/plate with and without metabolic activation
preincubation test: 10, 33, 100, 333, 1000, 2500 µg/plate with and without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: with rat S-9: 2-aminoanthracene: TA tester strains, 2.5 µg; E.coli WP2uvrA, 60 µg
- Remarks:
- with S9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-methyl-N'-nitro-N-nitrosoguanidine (TA1535, TA100: 5 µg/plate), 4-nitro-o-phenylendiamine (TA98: 10 µg/plate), 9-aminoacridine (TA1537, 100 µg/plate), 4-nitroquinoline-N-oxide (E. coli WP2 uvrA, 5 µg/plate)
- Remarks:
- without S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: standard plate test and preincubation test
DETERMINATION OF CYTOTOXICITY
- Method: reduced background growth - Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results:
negative - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well-documented study, but not according to established guidelines.
- Principles of method if other than guideline:
- E. coli reverse mutation assay according to Demerec (1951), Bertani (1951).
- GLP compliance:
- no
- Type of assay:
- bacterial gene mutation assay
- Species / strain / cell type:
- E. coli, other: B/Sd-4/1,3,4,5 and B/Sd-4/3,4
- Additional strain / cell type characteristics:
- other: streptomycin-dependant strains
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 0.025 - 0.30%
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- no
- Details on test system and experimental conditions:
- - Number of replicates: 3 hrs exposure, 5-10 replicates/dose
- Species / strain:
- E. coli, other: B/Sd-4/1,3,4,5 and B/Sd-4/3,4
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not examined
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Study seems to be performed according to established test procedures, but report too limited in detail.
- Principles of method if other than guideline:
- Bacterial reverse mutation assay (e.g. Ames test), plate count
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: Salmonella typhimurium TA98, TA100, TA1535, TA1537
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- 0.1, 1 and 10 mg/plate
- Untreated negative controls:
- yes
- Remarks:
- buffer solution
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 0.01 µg/plate AF2 without metabolic activation was used as a positive control for TA100 and TA 98, 100 µg/plate 9-aminoacridine without metabolic activation was used as a positive control for TA 1537, and 2 µg/plate 2-aminoanthracene with metabolic activa
- Details on test system and experimental conditions:
- plate incorporation
- Species / strain:
- S. typhimurium, other: TA98, TA100, TA1535, TA1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 10 mg/plate
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Endpoint:
- in vitro DNA damage and/or repair study
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented publication report which meets basic scientific principles
- Principles of method if other than guideline:
- Rec assay described by Kada et al. (1972)
- GLP compliance:
- no
- Type of assay:
- Bacillus subtilis recombination assay
- Species / strain / cell type:
- other: Bacillus subtilis H17 and M45
- Additional strain / cell type characteristics:
- other: H17 is recombination-repair-proficient, trp-deficient and arg-deficient. M45 is recombinant-repair-deficient, trp-deficient and arg-deficient.
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- 0.005-0.5 M
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Species / strain:
- bacteria, other: Bacillus subtilis H17 and M45
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
Referenceopen allclose all
PRECIPITATION CONCENTRATION:
156.3 µg active ingredient/ml (except experiment II after 18h preparation interval without S9 mix where precipitation occurred at 78.1 µg/ml and above)
Summary Table
|
|
relative |
relative |
mutant |
|
relative |
relative |
mutant |
|
|
|
conc. µg |
S9 |
cloning |
cloning |
colonies/ |
induction |
cloning |
cloning |
colonies/ |
induction |
|
per mL |
mix |
efficiency I |
efficiency II |
106 cells |
factor |
efficiency I |
efficiency II |
106 cells |
factor |
|
|
% |
% |
|
% |
% |
|
|||
column |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
Experiment I / 4 h treatment |
culture I |
culture II |
||||||||
Solvent control with water |
- |
100.0 |
100.0 |
18.4 |
1.0 |
100.0 |
100.0 |
17.1 |
1.0 |
|
Positive control with |
150.0 |
- |
76.2 |
94.8 |
137.7 |
7.5 |
84.7 |
86.2 |
132.3 |
7.7 |
Test item |
28.1 |
- |
98.4 |
114.2 |
15.4 |
0.8 |
92.7 |
104.2 |
13.0 |
0.8 |
Test item |
56.3 |
- |
100.0 |
110.3 |
12.0 |
0.7 |
97.1 |
98.0 |
16.8 |
1.0 |
Test item |
112.5 |
- |
102.8 |
101.8 |
16.7 |
0.9 |
88.2 |
96.3 |
15.5 |
0.9 |
Test item |
225.0 |
- |
87.2 |
102.0 |
21.5 |
1.2 |
76.9 |
95.5 |
19.9 |
1.2 |
Test item |
337.5 |
- |
0.2 |
98.4 |
14.6 |
0.8 |
8.8 |
89.2 |
20.5 |
1.2 |
Test item |
450.0 |
- |
0.0 |
culture was not continued# |
0.0 |
culture was not continued# |
||||
Solvent control with water |
+ |
100.0 |
100.0 |
24.6 |
1.0 |
100.0 |
100.0 |
17.9 |
1.0 |
|
Positive control with DMBA |
1.1 |
+ |
43.9 |
89.0 |
636.4 |
25.9 |
36.6 |
99.5 |
620.9 |
34.7 |
Test item |
56.3 |
+ |
94.4 |
culture was not continued## |
97.3 |
culture was not continued## |
||||
Test item |
112.5 |
+ |
89.5 |
94.1 |
16.9 |
0.7 |
95.7 |
105.9 |
22.3 |
1.2 |
Test item |
225.0 |
+ |
94.1 |
89.8 |
17.6 |
0.7 |
94.2 |
85.8 |
20.6 |
1.2 |
Test item |
450.0 |
+ |
84.7 |
90.5 |
16.3 |
0.7 |
94.5 |
81.5 |
20.9 |
1.2 |
Test item |
675.0 |
+ |
88.5 |
114.3 |
13.2 |
0.5 |
93.6 |
92.6 |
17.9 |
1.0 |
Test item |
900.0 |
+ |
85.0 |
85.7 |
27.8 |
1.1 |
92.9 |
96.4 |
15.5 |
0.9 |
Experiment II / 24 h treatment |
culture I |
culture II |
||||||||
Solvent control with water |
- |
100.0 |
100.0 |
13.7 |
1.0 |
100.0 |
100.0 |
14.1 |
1.0 |
|
Positive control with |
75.0 |
- |
92.5 |
97.7 |
132.5 |
9.7 |
102.2 |
93.2 |
105.6 |
7.5 |
Test item |
28.1 |
- |
104.7 |
culture was not continued## |
101.8 |
culture was not continued## |
||||
Test item |
56.3 |
- |
102.5 |
95.7 |
16.9 |
1.2 |
102.2 |
69.3 |
18.8 |
1.3 |
Test item |
112.5 |
- |
88.0 |
94.5 |
17.4 |
1.3 |
102.7 |
97.8 |
9.0 |
0.6 |
Test item |
225.0 |
- |
95.1 |
88.7 |
23.2 |
1.7 |
102.0 |
71.3 |
17.4 |
1.2 |
Test item |
450.0 |
- |
94.1 |
84.2 |
23.6 |
1.7 |
101.4 |
65.3 |
17.7 |
1.3 |
Test item |
675.0 |
- |
43.3 |
90.9 |
16.2 |
1.2 |
102.9 |
63.5 |
28.4 |
2.0 |
Experiment II / 4 h treatment |
culture I |
culture II |
||||||||
Solvent control with water |
+ |
100.0 |
100.0 |
13.7 |
1.0 |
100.0 |
100.0 |
16.1 |
1.0 |
|
Positive control with DMBA |
1.1 |
+ |
55.9 |
73.5 |
809.9 |
59.1 |
51.2 |
78.8 |
595.5 |
36.9 |
Test item |
112.5 |
+ |
114.6 |
78.2 |
20.1 |
1.5 |
95.6 |
90.4 |
22.6 |
1.4 |
Test item |
225.0 |
+ |
91.3 |
101.5 |
24.6 |
1.8 |
107.2 |
98.0 |
14.5 |
0.9 |
Test item |
450.0 |
+ |
95.5 |
109.1 |
22.9 |
1.7 |
99.1 |
83.9 |
20.5 |
1.3 |
Test item |
900.0 |
+ |
111.7 |
99.4 |
26.1 |
1.9 |
112.6 |
80.5 |
20.8 |
1.3 |
Test item |
1350.0 |
+ |
10.6 |
100.7 |
11.4 |
0.8 |
7.4 |
102.9 |
8.8 |
0.5 |
Test item |
1800.0 |
+ |
0.0 |
culture was not continued# |
0.0 |
culture was not continued# |
# culture not continued due to exceedingly strong toxic effects
## culture was not continued since a minimum of only four analysable concentrations is required
Table 1: Results of tester strains TA1537 and TA98 with and without metabolic activation
(*reduced background growth)
|
|
TA 1537 |
TA 98 |
||||||||||
Dose [µg/plate] |
S-9 mix |
Standard Test |
Preincubation Test |
Standard Test |
Preincubation Test |
||||||||
0 |
+ |
9 |
7 |
6 |
8 |
5 |
7 |
28 |
25 |
21 |
21 |
24 |
22 |
10 |
+ |
- |
- |
- |
6 |
8 |
6 |
- |
- |
- |
28 |
21 |
19 |
33 |
+ |
8 |
6 |
9 |
6 |
7 |
8 |
28 |
19 |
27 |
28 |
17 |
26 |
100 |
+ |
8 |
8 |
7 |
9 |
4 |
7 |
25 |
23 |
18 |
24 |
21 |
20 |
333 |
+ |
10 |
5 |
8 |
5 |
8 |
7 |
22 |
25 |
26 |
20 |
15 |
21 |
1000 |
+ |
8 |
5 |
7 |
4 |
5 |
4 |
21 |
23 |
24 |
17 |
10 |
11 |
2500 |
+ |
7 |
7 |
5 |
2* |
2* |
3* |
18 |
14 |
17 |
4* |
4* |
5* |
5000 |
+ |
2* |
5* |
5* |
- |
- |
- |
10* |
8* |
6* |
- |
- |
- |
2-aminoanthracene |
+ |
155 |
129 |
111 |
164 |
119 |
138 |
668 |
634 |
529 |
665 |
578 |
634 |
0 |
- |
8 |
6 |
6 |
5 |
7 |
7 |
21 |
17 |
19 |
21 |
15 |
18 |
10 |
- |
- |
- |
- |
7 |
5 |
6 |
- |
- |
- |
17 |
19 |
16 |
33 |
- |
8 |
5 |
9 |
8 |
5 |
4 |
18 |
23 |
14 |
20 |
18 |
14 |
100 |
- |
7 |
6 |
5 |
5 |
7 |
4 |
15 |
22 |
21 |
16 |
19 |
21 |
333 |
- |
8 |
6 |
6 |
6 |
5 |
6 |
17 |
18 |
20 |
21 |
15 |
14 |
1000 |
- |
7 |
8 |
5 |
2* |
1* |
2* |
20 |
14 |
18 |
9* |
5* |
5* |
2500 |
- |
3 |
5 |
5 |
0* |
0* |
0* |
12 |
13 |
17 |
0* |
0* |
0* |
5000 |
- |
2* |
4* |
1* |
- |
- |
- |
8* |
5* |
5* |
- |
- |
- |
AAC(TA1537)/NOPD(TA98) |
- |
336 |
378 |
329 |
335 |
412 |
368 |
558 |
534 |
611 |
551 |
539 |
571 |
Table 2: Results of tester strains TA1535 and TA100 with and without metabolic activation
(*reduced background growth)
|
|
TA 1535 |
TA 100 |
||||||||||
Dose [µg/plate] |
S-9 mix |
Standard Test |
Preincubation Test |
Standard Test |
Preincubation Test |
||||||||
0 |
+ |
16 |
13 |
14 |
12 |
13 |
10 |
92 |
96 |
100 |
85 |
77 |
86 |
10 |
+ |
- |
- |
- |
11 |
14 |
11 |
- |
- |
- |
89 |
86 |
80 |
33 |
+ |
16 |
13 |
15 |
10 |
12 |
12 |
103 |
102 |
81 |
80 |
74 |
95 |
100 |
+ |
15 |
14 |
12 |
13 |
14 |
13 |
109 |
90 |
113 |
81 |
93 |
83 |
333 |
+ |
20 |
11 |
11 |
14 |
10 |
11 |
100 |
91 |
103 |
71 |
83 |
81 |
1000 |
+ |
12 |
11 |
15 |
8 |
9 |
9 |
92 |
111 |
90 |
55 |
78 |
65 |
2500 |
+ |
10 |
10 |
8 |
2* |
5* |
5* |
89 |
80 |
73 |
40* |
51* |
46* |
5000 |
+ |
8* |
5* |
8* |
- |
- |
- |
46* |
48* |
40* |
- |
- |
- |
2-aminoanthracene |
+ |
126 |
193 |
164 |
178 |
136 |
154 |
882 |
739 |
812 |
- |
- |
- |
0 |
- |
10 |
13 |
9 |
12 |
10 |
10 |
100 |
85 |
97 |
71 |
69 |
80 |
10 |
- |
- |
- |
- |
11 |
10 |
12 |
- |
- |
- |
76 |
75 |
88 |
33 |
- |
13 |
11 |
10 |
13 |
9 |
10 |
88 |
100 |
90 |
68 |
71 |
82 |
100 |
- |
10 |
13 |
10 |
11 |
10 |
14 |
86 |
93 |
88 |
87 |
79 |
73 |
333 |
- |
12 |
12 |
9 |
7 |
13 |
13 |
105 |
85 |
87 |
72 |
80 |
71 |
1000 |
- |
9 |
10 |
12 |
2* |
1* |
1* |
76 |
79 |
76 |
16* |
11* |
14* |
2500 |
- |
11 |
8 |
8 |
0* |
0* |
0* |
70 |
57 |
66 |
0* |
0* |
0* |
5000 |
- |
7* |
3* |
6* |
- |
- |
- |
33* |
30* |
24* |
- |
- |
- |
MNNG(TA1535 +TA100) |
- |
819 |
802 |
915 |
668 |
712 |
731 |
773 |
813 |
761 |
- |
- |
- |
Table 3: Results of E.coli WP2 uvrA with and without metabolic activation (*reduced background growth)
|
|
E. coli WP2 uvrA |
|||||
Dose [µg/plate] |
S-9 mix |
Standard Test |
Preincubation Test |
||||
0 |
+ |
44 |
45 |
39 |
40 |
37 |
37 |
10 |
+ |
- |
- |
- |
38 |
38 |
37 |
33 |
+ |
41 |
38 |
51 |
37 |
36 |
34 |
100 |
+ |
45 |
42 |
40 |
38 |
41 |
35 |
333 |
+ |
40 |
41 |
36 |
40 |
39 |
31 |
1000 |
+ |
47 |
36 |
45 |
17 |
14 |
21 |
2500 |
+ |
33 |
29 |
32 |
12* |
15* |
14* |
5000 |
+ |
17* |
14* |
14* |
- |
- |
- |
2-aminoanthracene |
+ |
265 |
228 |
255 |
247 |
258 |
264 |
0 |
- |
32 |
38 |
41 |
40 |
33 |
35 |
10 |
- |
- |
- |
- |
40 |
30 |
37 |
33 |
- |
45 |
39 |
33 |
31 |
44 |
32 |
100 |
- |
36 |
41 |
42 |
36 |
35 |
37 |
333 |
- |
41 |
36 |
29 |
31 |
32 |
34 |
1000 |
- |
38 |
41 |
45 |
26 |
25 |
20 |
2500 |
- |
32 |
28 |
18 |
7* |
8* |
8* |
5000 |
- |
12* |
14* |
14* |
- |
- |
- |
4-NQO |
- |
559 |
688 |
634 |
731 |
712 |
644 |
MNNG: N-methyl-N'-nitro-N-nitrosoguanidine
NOPD: 4-nitro-o-phenylendiamine
AAC: 9-aminoacridine
4NQO: 4-nitroquinoline-N-oxide
mutant
frequency (mutants per 10E6 bacteria):
conc. (%)
mut.freq.(treated) mut.freq.(control) survival (%)
0.025 5.9
6.3
66
0.100 2.4
5.3
33
0.050 8.7
6.3
27
0.100 6.6
6.1
16
0.100 11.4
6.2
4.6
0.150 2.0
6.2
3
0.300 0.0
7.0
0.11
Genetic toxicity in vivo
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study was performed similar to OECD TG 475, with the restriction that no positive controls were used.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- not specified
- GLP compliance:
- no
- Type of assay:
- chromosome aberration assay
- Species:
- mouse
- Strain:
- other: BDF1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Age: 9 weeks
- Route of administration:
- oral: feed
- Duration of treatment / exposure:
- 24 hours
- Frequency of treatment:
- once, 4 mg/kg bw colchicine was administered intraperitoneally 2 hours before necropsy.
- Post exposure period:
- sampling time was 24 h after administration
- Remarks:
- Doses / Concentrations:
740-1340 mg/kg bw (7 graduated levels)
Basis:
nominal conc. - No. of animals per sex per dose:
- 4 - 6
- Control animals:
- yes, concurrent vehicle
- Tissues and cell types examined:
- femur bone marrow cells
- Evaluation criteria:
- The chromosomes were examined blind by three persons. Slides from femur bone marrow cells were prepared according to standard methods, and 100 metaphases per animal analyzed for chromosomal aberrations (including gaps, breaks, deletions, and exchanges).
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
Reference
MUTANT/ABERRATION/mPCE/ POLYPLOIDY FREQUENCY:
No significant increase of chromosomal aberrations compared to negative control even at dosage levels exceeding the M.T.D. of 940 mg/kg bw.
Additional information
The in-vitro genetic toxicity of disodium metasilicate nonahydrate was investigated in the Ames test (BASF SE, 2012).The standard plate test and the preincubation test were conducted each with S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvrA in the presence and absence of a metabolic activation system. Concentrations up to 5000 µg/plate were used for the standard plate test and concentrations up to 2500 µg/plate for the preincubation test. The test substance did not induce reversions in any of the S. typhimurium strains or in E. coli WP2 uvrA with or without metabolic activation.
All other in vitro mutagenicity tests with bacteria were negative. Sodium silicate (MR = 3.3) also did not induce chromosomal aberrations and HPRT mutations in V79 mammalian cells in vitro, both in the presence and the absence of metabolic activation. In vivo, sodium metasilicate did not induce chromosome aberrations in the bone marrow of mice. From the available results it can be concluded that there is no evidence of a genotoxic potential for potassium silicate.
Short description of key information:
in vitro: negative
in vivo: negative
Endpoint Conclusion:
Justification for classification or non-classification
The available data is conclusive but not sufficient for classification.
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