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EC number: 466-380-9 | CAS number: 52350-17-1
- 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
Description of key information
Negative, OECD 471, Bowles, 2004
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11 Aug-24 Nov 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- Adopted 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- EC Commissiion Directive 2000/32/EC
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United kingdom, London, England
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his operon (for S. typhimurium) and trp operon (for E. coli)
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbitone/ β-naphthoflavone
- Test concentrations with justification for top dose:
- First experiment: 50, 150, 500, 1500 and 5000 µg/plate with and without metabolic activation
Second experiment: 50, 150, 500, 1500 and 5000 µg/plate with and without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test material was non-soluble in distilled water, dimethyl sulfoxide, acetone, dimethyl formamide, ethanol and acetonitrile at 50 mg/mL and tetrahydrofuran at 200 mg/mL in solubility checks. It formed the best doseable suspension in dimethyl sulfoxide, and this was selected as the vehicle of choice.
- Prior to use, the solvent was dried using molecular seives. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- other: 2-Aminoanthracene (2AA) (+S9)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (direct plate incorporation)
DURATION
- Exposure duration: 37 °C for 48 h
NUMBER OF REPLICATIONS: triplicates each in two independent experiments
DETERMINATION OF CYTOTOXICITY
- Method: Inspection of the bacterial background lawn - Rationale for test conditions:
- The test material caused no reduction in the growth of the bacterial background lawn at any dose level. The test material therefore, was tested up to the maximum recommended dose level of 5000 µg/plate
- Evaluation criteria:
- The test material may be considered positive in this test if the following criteria are met:
The test material should have induced a reproducible, dose-related and statistically (Dunnett's method of linear regression) significant increase in the revertant count in at least one strain of bacteria. - Statistics:
- Mean values and standard deviation were calculated.
- 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:
- not examined
- 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:
- not examined
- Positive controls validity:
- valid
- 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:
- not examined
- 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:
- not examined
- 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:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Other confounding effects: A grey colour was observed at 5000 µg/plate with an associated black precipitate visible only with the use of a light microscope at 5000 µg/plate. These observations did not prevent the scoring of revertant colonies.
RANGE-FINDING/SCREENING STUDIES: The test material dose range was the same for both the range-finding and the main tests.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation)
- Negative (solvent/vehicle) historical control data:
- Positive historical control data:
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Combined Vehicle and Untreated Control Values 2002
TA100 TA1535 WP2uvrA- TA98 TA1537
-S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9
Mean 91 100 20 17 23 27 22 35 12 17
SD 16.6 18.0 5.5 4.3 4.8 5.3 5.2 6.8 4.0 4.7
Min 61 68 8 8 10 14 11 13 4 5
Max 160 162 38 37 47 45 44 66 29 38
Values 939 742 912 718 685 521 946 749 918 718
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Positive Control Values 2002
TA100 TA1535 WP2uvrA- TA98 TA1537
-S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9
Mean 460 1880 347 310 621 866 136 239 1953 453
SD 118.2 594.3 204.0 119.7 235.5 350.5 38.2 74.7 803.1 145.9
Min 235 499 80 91 185 210 66 91 486 140
Max 952 3397 1985 810 1295 3406 323 507 4622 1365
Values 190 190 188 186 169 168 192 192 188 184
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Combined Vehicle and Untreated Control Values 2003
TA100 TA1535 WP2uvrA- TA98 TA1537
-S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9
Mean 98 106 20 15 23 28 20 30 10 14
SD 20.7 23.4 8.5 3.9 5.6 7.0 5.1 7.1 3.9 5.0
Min 61 64 8 7 11 13 10 15 3 3
Max 165 191 45 39 44 57 52 53 26 32
Values 882 735 838 690 686 539 877 721 838 678
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Positive Control Values 2003
TA100 TA1535 WP2uvrA- TA98 TA1537
-S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9 -S9 +S9
Mean 429 1529 297 305 649 656 174 249 1273 370
SD 108.1 493.1 156.8 82.6 175.7 264.4 64.4 72.2 623.1 109.9
Min 197 485 98 162 273 136 64 87 262 148
Max 849 3662 1099 625 1198 1373 410 465 3704 759
Values 160 160 156 156 150 150 162 162 155 155
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - Conclusions:
- Interpretation of results: negative -- the test material was considered to be non-mutagenic under the conditions of this study.
- Executive summary:
In a reverse gene mutation assay in bacterial strains were exposed to the test itme in DMSO (as an undissolved suspension) at concentrations of 50, 150, 500, 1500 and 5000 µg/plate the test was conducted in the presence and absence of S9 mix.
The test item was tested up to maximum recommended concentration of 5000 µg/plate.
It was concluded that the test item did not have mutagenic potential.
Reference
Test Results: Range-Finding Test
EXPERIMENT 1 (Standard Plate Test, SPT) |
|||||
S9-Mix |
Without |
||||
Test Item (mg/plate) |
Base-pair substitution type |
Frameshift type |
|||
TA100 |
TA1535 |
WP2uvrA- |
TA98 |
TA1537 |
|
VC |
85±13.0 |
19±12.4 |
22±5.5 |
22±5.5 |
13±4.5 |
50 |
84±9.0 |
20±1.5 |
14±2.1 |
27±5.2 |
18±2.0 |
150 |
81±7.5 |
20±7.0 |
13±5.5 |
20±2.0 |
15±3.0 |
500 |
71±11.8 |
21±6.4 |
17±4.0 |
22±8.4 |
11±5.0 |
1500 |
79±7.2 |
23±2.0 |
17±4.5 |
24±7.5 |
14±4.0 |
5000 |
85±5.6 |
21±4.0 |
20±4.2 |
20±3.8 |
16±4.0 |
PC (mg/plate) |
ENNG (3) |
ENNG (5) |
EENG (2) |
4NQO (0.2) |
9-AA (80) |
586±25.6 |
526±91.0 |
899±32.5 |
180±24.7 |
574±53.3 |
|
S9-Mix |
With |
||||
Test Item (mg/plate) |
Base-pair substitution type |
Frameshift type |
|||
TA100 |
TA1535 |
WP2uvrA- |
TA98 |
TA1537 |
|
VC |
98±6.5 |
13±4.5 |
24±1.0 |
36±1.5 |
14±5.3 |
50 |
97±6.9 |
12±1.0 |
22±0.6 |
27±2.0 |
14±4.2 |
150 |
96±10.2 |
9±3.1 |
17±7.1 |
27±6.1 |
16±3.6 |
500 |
87±15.5 |
8±1.5 |
21±1.5 |
21±4.6 |
11±5.3 |
1500 |
89±13.2 |
10±1.5 |
20±6.2 |
29±2.6 |
15±2.9 |
5000 |
104±12.3 |
12±0.6 |
25±6.7 |
28±4.9 |
20±4.7 |
PC (mg/plate) |
2-AA (1) |
2-AA (2) |
2-AA (10) |
BP (5) |
2-AA (2) |
637±37.2 |
424±16.1 |
403±6.9 |
239±20.0 |
278±36.3 |
VC = Vehicle control; PC = Positive control
EENG = N-ethyl-N-nitro-N-nitrosoguanidine
4NQO = 4-Nitroquinoline-1-oxide
9-AA = 9-Aminoacridine
2-AA = 2-Aminoanthracene
BP = Benzo(a)pyrene
Test Results: Main Test
EXPERIMENT 2 (Standard Plate Test, SPT) |
|||||
S9-Mix |
Without |
||||
Test Item (mg/plate) |
Base-pair substitution type |
Frameshift type |
|||
TA100 |
TA1535 |
WP2uvrA- |
TA98 |
TA1537 |
|
VC |
71±6.4 |
33±4.5 |
27±7.2 |
21±2.1 |
18±5.5 |
50 |
72±8.7 |
18±2.5 |
26±6.1 |
19±4.9 |
13±4.2 |
150 |
72±7.6 |
38±9.7 |
22±2.5 |
18±4.4 |
16±7.4 |
500 |
60±6.7 |
31±9.5 |
25±5.2 |
18±6.1 |
17±1.0 |
1500 |
69±5.0 |
42±9.2 |
30±8.7 |
15±4.5 |
17±2.5 |
5000 |
74±6.5 |
39±13.7 |
21±2.1 |
20±2.0 |
18±1.0 |
PC (mg/plate) |
ENNG (3) |
ENNG (5) |
EENG (2) |
4NQO (0.2) |
9-AA (80) |
402±22.4 |
386±84.1 |
1133±67.5 |
215±16.7 |
612±120.1 |
|
S9-Mix |
With |
||||
Test Item (mg/plate) |
Base-pair substitution type |
Frameshift type |
|||
TA100 |
TA1535 |
WP2uvrA- |
TA98 |
TA1537 |
|
VC |
89±25.0 |
11±1.5 |
17±4.5 |
27±8.5 |
21±1.5 |
50 |
76±9.5 |
8±1.2 |
25±3.6 |
21±2.0 |
18±5.2 |
150 |
73±7.1 |
12±5.5 |
25±3.6 |
27±10.1 |
27±3.5 |
500 |
70±7.0 |
15±2.9 |
14±1.7 |
24±1.2 |
19±6.9 |
1500 |
70±4.4 |
8±0.6 |
18±6.8 |
29±3.5 |
20±3.8 |
5000 |
72±10.5 |
12±6.1 |
20±2.3 |
27±7.5 |
17±1.5 |
PC (mg/plate) |
2-AA (1) |
2-AA (2) |
2-AA (10) |
BP (5) |
2-AA (2) |
967±74.1 |
215±27.0 |
430±61.3 |
178±17.0 |
329±51.0 |
VC = Vehicle control; PC = Positive control
EENG = N-ethyl-N-nitro-N-nitrosoguanidine
4NQO = 4-Nitroquinoline-1-oxide
9-AA = 9-Aminoacridine
2-AA = 2-Aminoanthracene
BP = Benzo(a)pyrene
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Mode of Action Analysis / Human Relevance Framework
Not relevant.
Additional information
AMES study 2004 - In a reverse gene mutation assay in bacterial strains were exposed to the test itme in DMSO (as an undissolved suspension) at concentrations of 50, 150, 500, 1500 and 5000 µg/plate the test was conducted in the presence and absence of S9 mix.
The test item was tested up to maximum recommended concentration of 5000 µg/plate.
It was concluded that the test item did not have mutagenic potential.
The study was conducted on the particulate nanoform (i.e. not the dissolved form). Based on dissolution study results (Rosenfeldt, 2021, Section 4) this aligns with the draft ECHA guidance (Appendix R7-1 for nanoforms applicable to Chapter R7a and R7c Endpoint specific guidance, draft v3.0, 2021), whereby testing on the nanoform should be conducted if the nanoform is not highly soluble in water (>33,3 g/L) and/or does not have a half-life of water dissolution ≤ 10 min (Appendix R7-1 for nanoforms applicable to Chapter R7a and R7c Endpoint specific guidance, draft v3.0, 2021; Figure 1). This is further supported by the lack of dissolution seen in any vehicle and at pH 4 (relevant gut pH) seen during the dissolution study (Section 4, Rosenfeldt, 2021).
In accordance with the updated legislation (Regualtion (EC) No. 1907/2006) Section for nanoforms "The [AMES] study does not need to be conducted for nanoforms where it is not appropriate. In this case other studies involving one or more in vitro mutagenicity study(ies) in mammalian cells (Annex VIII, sections 8.4.2. and 8.4.3 or other internationally recognised in vitro methods) shall be provided." In order to further support the results of the OECD 471 (AMES test), a confirmatory study is being conducted, that of an OECD 490 is ongoing, this test is considered appropriate for nanoforms and in line with ECHA guidance may provide evidence that the results from the AMES were appropriate (ECHA Appendix R7-1 for nanomaterials applicable to Chapter R7a and R7c Endpoint specific guidance - draft v3.0 2021).
Justification for classification or non-classification
Interpretation of results: negative -- the test material was considered to be non-mutagenic under the conditions of this study. No requirement to classify under Regulation (EC) No. 1272/2008.
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