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EC number: 215-691-6 | CAS number: 1344-28-1
Genetic toxicity: in vitro
Administrative data
- 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:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay
- Author:
- Balasubramanyam, A., et al.
- Year:
- 2 010
- Bibliographic source:
- Toxicology in Vitro 24: 1871-1876
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 2020
- Deviations:
- yes
- Remarks:
- No test concentration (< 5 µg/plate) was insoluble in the final treatment mixture. No justificatin provided for not performing a confirmation of negative results; no data, if the efficacy of the S9 mix was chararcterized by a second mutagen.
- GLP compliance:
- not specified
- Remarks:
- The investigation was reported in a scientific paper without specifying whether GLP conditions were applied.
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Aluminium oxide
- EC Number:
- 215-691-6
- EC Name:
- Aluminium oxide
- Cas Number:
- 1344-28-1
- Molecular formula:
- Al2O3
- IUPAC Name:
- oxo[(oxoalumanyl)oxy]alumane
Constituent 1
Method
- Target gene:
- his operon
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium, other: 97a
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- S. typhimurium TA 100
- Species / strain / cell type:
- S. typhimurium TA 98
- Species / strain / cell type:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- method of preparation of S9 mix: The S9 mix was prepared just before use by adding 900 µL of co-factors (5.2 mM D-glucose-6-phosphate, 4.4 mM nicotinamide adenine dinucleotide phosphate, 18 mM MgCl2, 28 mM KCl, 90 mM Na2HPO4.H2O, 8 mM NaH2PO4.H2O) and 100 µL S9 fraction. - Test concentrations with justification for top dose:
- 0.02, 0.04, 0.075, 0.15, 0.3, 0.6, 1.25 and 2.5 µg/plate with and without metabolic activation in all strains
The test material precipitated at concentrations higher than 2.5 µg/plate. Thus, this concentration was chosen as maximum one to test. - Vehicle / solvent:
- - Vehicle used: DMSO/H2O 1:1
The test material was suspended in the vehicle and ultrasonicated for 10 min.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO/H2O 1:1 (v/v)
- True negative controls:
- yes
- Remarks:
- DMSO
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- mitomycin C
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: sextuplicates
- Number of independent experiments : single experiment
METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding: approx. 1E+09 bacterial cells/mL
- Test substance added in: preincubation mixture
TREATMENT AND HARVEST SCHEDULE:
- Preincubation period: 30 min at 37 °C
- Exposure duration/duration of treatment: 48 h
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: reduction in the number of revertant colonies or a clearing of the background lawn in comparison with control plates - Evaluation criteria:
- A positive response in the test was defined as an increase (at least twofold above the control) in His+/wild revertant colonies in every strain.
- Statistics:
- Mean values and standard deviation were calculated. The one-way analysis of variance (one-way ANOVA), followed by Dunnett’s multiple comparison post test, was used to verify the significance of a positive response. A P value < 0.05 was considered statistically significant.
Results and discussion
Test resultsopen allclose all
- 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
- True negative controls validity:
- valid
- Positive controls validity:
- valid
- 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
- True negative controls validity:
- valid
- Positive controls validity:
- valid
- 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
- True negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium, other: 97a
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- STUDY RESULTS
- Concurrent positive control data : The positive control substances (SA, 2NF, 9AA, mitomycin C and 2AA) at µg levels increased the number of revertant colonies by several fold compared to the control, revealing the sensitivity of the system to detect a mutagenic effect.
For all test methods and criteria for data analysis and interpretation:
- Concentration-response relationship where possible : Even at the highest tested concentration no increase in the number of revertants was detected and thus no concentration-response relationship is evident.
- Statistical analysis; P-value : All positive control substances resulted in P < 0.01 vs. control (ANOVA).
Ames test:
- Signs of toxicity : All concentrations tested did not show any statistically significant decrease in the number of revertant colonies compared to the control and thus, they resulted in lack of cytotoxicity.
- Individual plate counts : no data
- Mean number of revertant colonies per plate and standard deviation : please refer to table 1
HISTORICAL CONTROL DATA: no data
Any other information on results incl. tables
Table 1. Test results for Al2O3-bulk
With or without S9-Mix |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate (n=6) ± standard deviation |
||||
TA100 |
TA1535 |
TA98 |
TA97a |
TA102 |
||
+ |
DMSO (50 µL/plate) |
153.3 ± 14.9 |
12.6 ± 5.6 |
23.3 ± 4.5 |
178.3 ± 11.5 |
320.6 ± 21.5 |
+ |
DMSO/H2O 1:1 (v/v) |
146.4 ± 16.2 |
13.3 ± 4.9 |
26.1 ± 5.3 |
169.2 ± 10.2 |
311.2 ± 22.2 |
+ |
20 |
154.6 ± 10.9 |
12.4 ± 3.2 |
24.3 ± 4.5 |
177.1 ± 14.5 |
319.0 ± 23.1 |
+ |
40 |
151.3 ± 9.0 |
13.4 ± 3.8 |
26.5 ± 4.0 |
178.6 ± 14.2 |
320.8 ± 21.3 |
+ |
75 |
154.7 ± 10.5 |
11.9 ± 5.8 |
24.6 ± 4.1 |
179.6 ± 11.8 |
322.1 ± 19.3 |
+ |
150 |
157.3 ± 10.1 |
12.6 ± 3.7 |
26.7 ± 4.8 |
176.2 ± 15.1 |
323.6 ± 21.1 |
+ |
300 |
152.2 ± 9.7 |
12.3 ± 6.1 |
24.1 ± 3.6 |
175.3 ± 11.5 |
320.3 ± 39.1 |
+ |
600 |
161.3 ± 10.5 |
13.3 ± 4.9 |
26.9 ± 6.2 |
175.3 ± 16.4 |
320.6 ± 27.2 |
+ |
1250 |
166.3 ± 11.2 |
13.9 ± 5.1 |
25.3 ± 5.5 |
171.2 ± 16.1 |
327.3 ± 24.5 |
+ |
2500 |
169.7 ± 9.8 |
13.2 ± 4.4 |
26.6 ± 4.4 |
174.5 ± 14.8 |
323.4 ± 22.3 |
+ |
Positive controls |
2AA |
2AA |
2AA |
2AA |
2AA |
Mean No. of colonies/plate ± SD |
695.6 ± 32.9* |
432.4 ± 27.9* |
208.9 ± 17.2* |
830.6 ± 36.4* |
1212 ± 82.5* |
|
- |
DMSO (50 µL/plate) |
102.3 ± 17.5 |
16.6 ± 5.0 |
25.3 ± 3.1 |
174.0 ± 19.8 |
254.0 ± 25.0 |
- |
DMSO/H2O 1:1 (v/v) |
104.6 ± 10.2 |
14.4 ± 3.9 |
23.1 ± 3.3 |
169.6 ± 15.5 |
241.2 ± 22.2 |
- |
20 |
106.0 ± 14.3 |
18.0 ± 3.0 |
26.1 ± 3.1 |
171.6 ± 14. |
241.1 ± 20.2 |
- |
40 |
99.3 ± 14.2 |
17.2 ± 5.2 |
23.3 ± 2.5 |
184.0 ± 24.5 |
264.0 ± 21.6 |
- |
75 |
112.6 ± 8.5 |
15.0 ± 5.1 |
26.3 ± 3.5 |
171.3 ± 19.6 |
251.0 ± 25.7 |
- |
150 |
108.3 ± 10.5 |
16.0 ± 2.6 |
23.3 ± 3.1 |
180.0 ± 22.0 |
267.3 ± 31.7 |
- |
300 |
116.0 ± 11.3 |
16.6 ± 4.1 |
25.1 ± 3.7 |
172.3 ± 19.0 |
268.6 ± 28.8 |
- |
600 |
126.0 ± 13.7 |
18.3 ± 3.5 |
24.3 ± 3.5 |
177.3 ± 17.7 |
277.3 ± 29.1 |
- |
1250 |
114.4 ± 12.3 |
17.7 ± 2.9 |
25.2 ± 2.8 |
180.1 ± 16.8 |
268.6 ± 30.1 |
- |
2500 |
121.4 ± 14.2 |
19.1 ± 3.1 |
26.7 ± 3.3 |
182.1 ± 15.4 |
271.4 ± 33.1 |
- |
Positive controls |
SA |
SA |
2NF |
9AA |
Mitomycin C |
Mean No. of colonies/plate ± SD |
483.6 ± 53.5* |
323.3 ± 26.5* |
95.3 ± 8.6* |
625.6 ± 43.4* |
1101 ± 84.02* |
|
SA = sodium azide
9AA = 9-aminoacridine
2NF = 2-nitrofluorene
2AA = 2-aminoanthracene
* P < 0.01 vs. Control (ANOVA)
Applicant's summary and conclusion
- Conclusions:
- Al2O3-bulk was negative in the Ames test in the S. typhimurium strains TA 97a, TA 98, TA 100, TA 1535 and TA102 up to and including a concentration of 2500 µg/plate. No cytotoxicity nor precipitation was noted in any of the tested concentrations.
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