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EC number: 238-851-7 | CAS number: 14782-75-3
Toxicological information
Genetic toxicity: in vitro
Currently viewing:
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 22 November 2017 to 7 February 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The Ames test was undertaken as a bridging study to demonstrate equivalence between the Target substance (XP 475) and the Source substance (XP 338; CAS 569318-35-0) for the read-across of other data. A full discussion of read-across and supporting data is given in the attached justification below.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 20 November 2003 to 14 December 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- XP 475 is an analogue of XP 338. An Ames test is used as a bridging study to demonstrate similarity of results for both substances.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- The substance is the Source of the read-across.
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S-9 mix
- Vehicle / solvent:
- Acetone
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- mitomycin C
- other: 2-Aminoanthracene, 1,8-Dihydroxyanthraquinone
- Details on test system and experimental conditions:
- Five concentrations of test material (50, 150, 500, 1500, and 5000 microgram per plate, were assayed in triplicate against each tester strain, using the direct plate incorporation method.
Bacterial cultures, followed by trace-histidine-supplemented top-agar, test material formulation, vehicle, or positive control, and either S9-mix or phosphate buffer.
The plates were incubated at 37 °C for 48 h, and the frequency of revertant colonies assessed using a colony counter. - Evaluation criteria:
- The test material is considered positive if it induces a reproducible, dose-related and statistically significant increase in the revertant count in at least one strain of bacteria.
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle 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
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle 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
- 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
- Positive controls validity:
- valid
- Conclusions:
- Test material non-mutagenic.
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 20 November 2003 to December 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- XP 475 is an analogue of XP 339. An Ames test is used as a bridging study to demonstrate similarity of results for both substances.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Test concentrations of 50, 150, 500, 1500 and 5000 microgram/plate were used in teh main experiment. The test material caused no visible reduction in the growth of the baterial background lawn at any dose level. No precipitate seen in the main experiment, although a light precipitate was seen in the preliminary experiment.
- Vehicle / solvent:
- Acetone
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- mitomycin C
- other: 2-Aminoanthracene, 1,8-Dihydroxyanthraquinone
- Evaluation criteria:
- The test material should induce a reproducible, dose-related and statistically significant increase in the revertant count in at least one strain of bacteria.
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle 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
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle 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
- Positive controls validity:
- valid
- Conclusions:
- Test material non-mutagenic.
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Principles of method if other than guideline:
- Not available.
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- 4 to 10,000 μg/plate
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Vehicle controls validity:
- not valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Conclusions:
- In a well conducted study ethyl acetoacetate did not induce gene mutations in bacteria in the
absence or presence of Aroclor-induced rat liver S-9 mix in doses ranging from 4 to 10,000
μg/plate.
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- genetic toxicity in vitro, other
- Remarks:
- Summary of in vitro and in vivo genetic toxicity tests for isopropanol.
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Specific details on test material used for the study:
- Test substance is a hydrolysis product of Target Substance.
- Species / strain:
- other: Summary of test results from various in vitro and in vivo studies
- Genotoxicity:
- negative
- Conclusions:
- Isopropanol is not a hazard for genotoxic effects.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- (ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium
- EC Number:
- 238-851-7
- EC Name:
- (ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium
- Cas Number:
- 14782-75-3
- Molecular formula:
- C12 H23 O5
- IUPAC Name:
- (ethyl 3-oxobutyrato-O1',O3)bis(propan-2-olato)aluminium
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- The substance is the Source of the read-across.
Method
Species / 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:
- S9 fraction of Phenobarbital (PB) and β-naphthoflavone (BNF)-induced rat liver
- Test concentrations with justification for top dose:
- Based on the results of the preliminary Concentration Range Finding Test (Informatory Toxicity Test) the following concentrations of the test item were prepared and investigated in the Initial and Confirmatory Mutation Tests: 5000; 1600; 500; 160; 50 and 16 μg/plate.
At the concentration choice the guideline criterion for soluble, non-toxic test compounds was taken into consideration where the recommended maximum test concentration is 5 mg/plate. - Vehicle / solvent:
- Acetone
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- methylmethanesulfonate
- other: 4-Nitro-1,2-phenylenediamine, NPD
- Details on test system and experimental conditions:
- The study included a Preliminary Solubility Test, a Preliminary Concentration Range Finding Test (Informatory Toxicity Test) an Initial Mutation Test (Plate Incorporation Test), and a Confirmatory Mutation Test (Pre-Incubation Test).
In the Preliminary Concentration Range Finding Test as well as in the Initial Mutation Test the plate incorporation method was used. - Evaluation criteria:
- 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.
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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle 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 nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Applicant's summary and conclusion
- Conclusions:
- Test material non-mutagenic.
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