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EC number: 811-188-6 | CAS number: 16184-79-5
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-01-20 to 2016-03-04
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Version / remarks:
- 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Guideline S2 (R1): Genotoxicity testing and data interpretation for pharmaceuticals intended for human use, June 2012
- Version / remarks:
- 2012
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 2,2-dimethyl-3-oxopropyl acetate
- EC Number:
- 811-188-6
- Cas Number:
- 16184-79-5
- Molecular formula:
- C7H12O3
- IUPAC Name:
- 2,2-dimethyl-3-oxopropyl acetate
- Test material form:
- liquid
Constituent 1
Method
- Target gene:
- The Salmonella typhimurium histidine (his) reversion system measures his- → his+ reversions. The Salmonella typhimurium strains are constructed to differentiate between base pair (TA1535, TA100) and frameshift (TA1537, TA98) mutations. The Escherichia coli WP2 uvrA (trp) reversion system measures trp– → trp+ reversions. The Escherichia coli WP2 uvrA strain detects mutagens that cause other base-pair substitutions (AT to GC).
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Trinova Biochem GmbH (Rathenau Str. 2 (earlier: Kerkrader Str. 10));
D-35394 Giessen, Germany
- Species / strain / cell type:
- E. coli WP2 uvr A
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Trinova Biochem GmbH (Rathenau Str. 2 (earlier: Kerkrader Str. 10));
D-35394 Giessen, Germany
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 fraction of Phenobarbital (PB) and β-naphthoflavone (BNF) induced rat liver
- Test concentrations with justification for top dose:
- Six (+S9 Mix) and seven (-S9 Mix) concentrations of the test item were tested in the main study. The test concentrations were:
-S9 Mix: 5000; 4000; 2000; 800; 320; 128 and 51.2 μg/plate;
+S9 Mix: 5000; 2000; 800; 320; 128 and 51.2 μg/plate.
Selection of the concentrations was done on the basis of a solubility test and a concentration range finding test (Informatory Toxicity Test). - Vehicle / solvent:
- - Vehicle used: DMSO
- Justification for choice of solvent/vehicle: The suitability of the solvent had been determined in the preliminary Solubility Test.
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-1,2-phenylene-diamine (NPD)
- Remarks:
- Strain: Salmonella TA 98; without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- Strain: Salmonella TA 100 and TA 1537; without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- Strain: Salmonella TA 1537; without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- Strain: E. coli WP2 uvrA; without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene (2AA)
- Remarks:
- Strain: all strains used; with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
A dose level is considered toxic if:
- the reduced revertant colony numbers are observed as compared to the mean vehicle control value and the reduction shows a dose-dependent relationship, and / or
- the reduced revertant colony numbers are below the historical control data range and / or
- pinpoint colonies appear and / or
- reduced background lawn development occurs
- other: The toxicity of the test item was determined with strains Salmonella typhimurium TA98 and TA100 in a pre-experiment. 7 concentrations were tested for toxicity and mutation induction with 3 plates each. The experimental conditions in this pre-experiment were the same as for the main experiment I (plate incorporation test) and included non-activated and S9 activated test conditions with appropriate positive and negative controls. The test item concentrations, including the controls (untreated, vehicle and positive reference) were tested in triplicate. In the toxicity test the concentrations examined were: 5000, 1600, 500, 160, 50, 16 and 5 μg/plate. - Rationale for test conditions:
- According to guidelines
- Evaluation criteria:
- The colony numbers on the control, positive control and the test plates were determined, the mean values, standard deviations and the mutation rates were calculated.
Mutation Rate = Mean revertants at the test item (or control) treatments / Mean revertrants of vehicle control
A test item is considered mutagenic if:
- a dose-related increase in the number of revertants occurs and/or;
- a reproducible biologically relevant positive response for at least one of the dose groups occurs in at least one strain with or without metabolic activation.
An increase is considered biologically relevant if:
- in strain TA100 the number of reversions is at least twice as high as the reversion rate of the vehicle control
- in strain TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA the number of reversions is at least three times higher than the reversion rate of the vehicle control.
According to the guidelines, the biological relevance of the results was the criterion for the interpretation of results, a statistical evaluation of the results was not regarded as necessary.
Criteria for a Negative Response:
A test article is considered non-mutagenic in this bacterial reverse mutation assay if it produces neither a dose-related increase in the number of revertants nor a reproducible biologically relevant positive response at any of the dose groups, with or without metabolic activation.
Results and discussion
Test resultsopen allclose all
- 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:
- positive
- 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
- Precipitation: No precipitation of the test item was observed on the plates in the examined bacterial strains at any examined concentration level (±S9 Mix) throughout the study.
HISTORICAL CONTROL DATA
- Positive historical control data: see "Any other information on results" table 1
- Negative historical control data: "Any other information on results" table 1
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Inhibitory effects of the test item (decreased number of revertant colony numbers and/or affected background lawn development) was not observed in any case.
Any other information on results incl. tables
Table 1 Historical control values for revertants/plate (for the period of 2008-2015)
|
|
Bacterial strains |
|||||
Historical control data of DMSO control |
-S9 |
|
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
E. coli |
Average |
20.9 |
101.4 |
10.3 |
7.9 |
24.9 |
||
SD |
3.5 |
26.2 |
1.4 |
2.5 |
4.9 |
||
Minimum |
10 |
65 |
3 |
2 |
11 |
||
Maximum |
39 |
150 |
23 |
20 |
44 |
||
+S9 |
|
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
E. coli |
|
Average |
27.1 |
114.7 |
12.0 |
8.8 |
34.2 |
||
SD |
4.0 |
19.3 |
1.5 |
2.1 |
5.2 |
||
Minimum |
15 |
71 |
4 |
3 |
16 |
||
Maximum |
48 |
161 |
24 |
20 |
56 |
||
Historical control data of positive control |
-S9 |
|
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
E. coli |
Average |
255.6 |
958.9 |
842.1 |
467.4 |
712.3 |
||
SD |
30.7 |
149.+ |
134.0 |
105.7 |
57.5 |
||
Minimum |
123 |
522 |
354 |
109 |
320 |
||
Maximum |
647 |
1927 |
1871 |
1498 |
1283 |
||
+S9 |
|
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
E. coli |
|
Average |
1224.8 |
1431.9 |
165.4 |
148.0 |
264.7 |
||
SD |
293.8 |
339.9 |
35.1 |
21.3 |
74.2 |
||
Minimum |
409 |
581 |
85 |
68 |
141 |
||
Maximum |
2587 |
2923 |
507 |
407 |
487 |
Applicant's summary and conclusion
- Conclusions:
- The reported data of this mutagenicity assay shows that under the experimental conditions reported, the test item (acting as direct mutagen, in absence of exogenous metabolic activation) induced gene mutations by base-pair substitution in the genome of the Salmonella typhimurium TA100 tester strain investigated. Therefore, the test item is considered mutagenic in this bacterial reverse mutation assay.
- Executive summary:
The test item was dissolved in dimethyl sulfoxide (DMSO). In the Initial and Confirmatory Mutation Tests the following concentrations were examined: -S9 Mix: 5000; 4000; 2000; 800; 320; 128 and 51.2 μg/plate; +S9 Mix: 5000; 2000; 800; 320; 128 and 51.2 μg/plate. An Additional Plate Incorporation Test was performed (in parallel with the pre-incubation test) with S. typhimurium TA100 in the absence of metabolic activation (-S9 Mix). In this additional experiment the corresponding Initial Mutation Test part was repeated with the same concentration levels. Bacteria In the Initial and Confirmatory Mutation Tests Salmonella typhimurium TA98, TA1537, TA1535 and TA100 strains and Escherichia coli WP2 uvrA were used. In the Additional Plate Incorporation Test the Salmonella typhimurium TA100 strain was investigated. Five bacterial strains were used to investigate the mutagenic potential of the test item in two independent experiments, in a plate incorporation test (experiment I, Initial Mutation Test) in a pre-incubation test (experiment II, Confirmatory Mutation Test). Each assay was conducted with and without metabolic activation (±S9 Mix). The concentrations, including the controls, were tested in triplicate. In the performed experiments positive and negative (vehicle) controls were run concurrently. In parallel with the Confirmatory Mutation Test an Additional Plate Incorporation Test (partial) was performed with Salmonella typhimurium TA100 in the absence of metabolic activation (-S9 Mix). In the performed experiments all of the validity criteria, regarding the investigated strains, negative and positive controls, S9 activity and number of investigated analyzable concentration levels were fulfilled. In the Initial Mutation Test following treatment with the test item significant, biological relevant revertant colony number increases, positive result was noticed at the concentration of 5000 μg/plate in S. typhimurium TA100 in the absence of exogenous metabolic activation (-S9 Mix). The revertant colony number increases showed clear dose-relationship at the further, lower concentration levels. The dose related tendencies, the unequivocal positive results were repeated in subsequent experiments: in the Additional Plate Incorporation Test, and in the Confirmatory Mutation Test. In the performed experiments inhibitory effect of the test item (decreased number of revertant colony numbers and/or affected background lawn development) was not observed in any case. No precipitation of the test item was observed on the plates in the examined bacterial strains at any examined concentration level (±S9 Mix) throughout the study.
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