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EC number: 904-155-3 | CAS number: -
- 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
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 3rd May 2012 to 17th August 2012.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted in accordance with GLP and OECD Guideline 471, with no deficiencies to affect the validity of the study.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- not applicable
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
- Deviations:
- not specified
- Principles of method if other than guideline:
- Not applicable.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 2,6-diethyl-2,6-bis(hydroxymethyl)heptane-1,3,5,7-tetrol; 2-ethyl-2-(hydroxymethyl)propane-1,3-diol; 2-ethyl-2-{[2-ethyl-3-hydroxy-2-(hydroxymethyl)propoxy]methyl}propane-1,3-diol
- EC Number:
- 904-155-3
- Molecular formula:
- C12H28O6 C12H26O5 C6H14O3
- IUPAC Name:
- 2,6-diethyl-2,6-bis(hydroxymethyl)heptane-1,3,5,7-tetrol; 2-ethyl-2-(hydroxymethyl)propane-1,3-diol; 2-ethyl-2-{[2-ethyl-3-hydroxy-2-(hydroxymethyl)propoxy]methyl}propane-1,3-diol
- Test material form:
- not specified
- Details on test material:
- - Name of test material (as cited in study report): HB TMP
- Analytical purity: 69%
- Composition of test material, percentage of components: 2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol] (CAS: 23235-61-2, EC No.: 245-509-0), Propylidynetrimethanol (CAS: 77-99-6, EC No.: 201- 074-9) and 2,2'-[methylenebis(oxymethylene)]bis[2-ethylpropane-1,3-diol] (CAS: 93983-16-5, EC No.: 301-304-9).
- Lot/batch No.: 7LTQA002
- Expiration date of the lot/batch: 8th May 2014
- Storage condition of test material: Stored at ambient temperature in the dark when not in use.
Constituent 1
Method
- Target gene:
- Histidine and tryptophan.
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):
- The S. typhimurium strains contain mutations in the histidine operon, thereby imposing the essential requirement for histidine in the growth medium. Three mutations in the histidine operon are involved his G 46 in TA 1535 and TA 100, his C 3076 in TA 1537 and his D 3052 in TA 98. All 4 strains also contain the deep rough (rfa) mutation.
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- E. coli WP2 uvr A
- Details on mammalian cell type (if applicable):
- The strain contains an ochre mutation in the trpE locus and can be mutated to tryptophan-independence either by a base-pair reversion of an A-T base-pair in the trpE locus, or more commonly, by a base-pair substitution within a number of transfer RNA loci elsewhere in the chromosome.
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- Preliminary toxicity test: 16.6, 49.8, 166, 498, 1659 and 4978 μg per plate
First mutation test: 16.6, 49.8, 166, 498, 1659 and 4978 μg per plate
Second mutation test: 17, 50, 167, 500, 1667 and 5000 μg per plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 2 μg per plate with S typhimurium TA 1535 and TA 1537, 0.5 μg per plate with S. typhimurium TA 98 and TA 100 and 20 μg per plate with E. coli WP2uvrA
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- Prepared in DMSO ; With S9 mix
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 1 μg per plate with S. typhimurium TA 1535 and TA 100
- Positive control substance:
- sodium azide
- Remarks:
- Prepared in water ; Without S9 mix
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 80 μg per plate with S. typhimurium TA 1537
- Positive control substance:
- 9-aminoacridine
- Remarks:
- Prepared in DMSO ; Without S9 mix
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 1 μg per plate with S. typhimurium TA 98
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Prepared in DMSO ; Without S9 mix
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 2 μg per plate with E. coli WP2uvrA
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- Prepared in DMSO ; Without S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation) and pre-incubation method.
The Direct Plate Incorporation Method was used in the initial toxicity testing to determine suitable exposure levels to be used for the subsequent mutation tests. In the initial toxicity testing, a single strain of bacteria, S. typhimurium TA 100 was used, and one plate per exposure level of test item was prepared.
In the mutation tests, Diluted agar (Difco Bacto-agar (0.6%, w/v), NaCl (0.6%, w/v)) was autoclaved and, just before use, were supplemented with sterile L-histidine.HCl (1.0 mM)/biotin (1.0 mM) was added at 50 mL per litre of soft agar for S. typhimurium. For E. coli, sterile L-tryptophan (1.35 mM) was added at 10 mL per litre of soft agar. These soft agars were thoroughly mixed and kept in a water bath set to maintain a temperature of 45°C.
For the Direct Plate Incorporation Method, soft agar (2 mL) was dispensed into a small plastic sterile tube. S9 mix or phosphate buffer (0.05 M, pH 7.4) (0.5 mL) was added, followed by the bacteria (0.1 mL) and, finally, the test solution. The tube contents were mixed, then poured on to minimal medium plates prepared in-house. The plates contained BBL Purified Agar (1.5%, 20 mL) in Vogel-Bonner Medium E (Vogel and Bonner, 1956) with glucose (2%, w/v).
For the Pre-incubation Method, S9 mix or phosphate buffer (0.05 M, pH 7.4) (0.5 mL) was dispensed into a small plastic sterile tube followed by the bacteria (0.1 mL) and, finally, the test solution. The tubes were then placed for 20 min in a shaking incubator set to maintain a temperature of 37°C. After incubation, soft agar (2 mL) was added to each tube. The tube contents were then mixed and poured onto minimal medium plates. When the soft agar had set, the plates were inverted and placed in an incubator set to maintain a temperature of 37°C for 3 days and then examined. The numbers of mutant colonies on each plate were determined and captured electronically in a validated software system. The plates were also examined microscopically for precipitates and for microcolony growth.
SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays):
NUMBER OF REPLICATIONS: All test items were tested in triplicate, (100 μL per plate), both in the absence and in the presence of S9 mix.
DETERMINATION OF CYTOTOXICITY
- Method: Colony count - Evaluation criteria:
- For S. typhimurium strains TA 1535, TA 1537, and TA 98 and for E. coli WP2uvrA, at least a doubling of the mean concurrent vehicle control value is required before mutagenic activity is suspected. For S. typhimurium strain TA 100, a 1.5-fold increase over the control value is required before mutagenic activity is suspected.
If the mean colony count on the vehicle control plates is less than 10, then a minimum count of 20 (representing a 2-fold increase over 10) is required before a response is registered. Rationale: As the vehicle control counts for strains with low spontaneous mutation rates (such as TA 1535, TA 1537 and particularly E. coli WP2uvrA) often range from 0 to 30, it is normal to have occasions where the vehicle mean is <10 while random treatment means are in the range 10 to 20. The use of the ‘minimum of 20’ rule avoids unnecessary repeat work due to strict application of the 2-fold rule.
A concentration-related response is also required for identification of a mutagenic effect. At high concentrations this relationship may be reversed because of, for example, toxicity of the test item to the bacteria, specific toxicity of the test item to the mutants, or inhibition of S9 enzymes (where a mutagen requires metabolic activation by the S9 mix). A response should be reproducible in an independent test. - Statistics:
- Not performed in this study.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation of HB TMP was observed at any concentration in either mutation test.
RANGE-FINDING/SCREENING STUDIES:
In the first test, conducted by the Direct Plate Incorporation Method, no toxicity to the bacteria was observed at any concentration of HB TMP. In the second test, conducted by the Pre-incubation Method, toxicity to all 5 strains was observed as a slight thinning of the background lawn of microcolonies. This observation was made at the highest concentration of 5000 μg per plate, only in the absence of S9 mix.
COMPARISON WITH HISTORICAL CONTROL DATA:
The vehicle and positive control groups were all within the normal/historical ranges for each bacterial strain and activation condition. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative with and without metabolic activation.
Under the conditions of this study, HB TMP is not considered mutagenic when tested on Salmonella typhimurium and Escherichia coli in the presence and absence of metabolic activation at concentrations up to the predetermined maximum of 5000 μg per plate. - Executive summary:
In a study to determine the mutagenic potential of HB TMP, a bacterial reverse mutation assay was conducted in accordance with OECD guideline 471. The test strains used were Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 and Escherichia coli WP2uvrA. DMSO was used as the vehicle and the positive controls included 2 -Aminoanthracene in the presence of S9 mix and Sodium azide, 9-Aminoacridine, 2-Nitrofluorene and N-Ethyl-N-nitro-N-nitrosoguanidine in the absence of S9 mix.
Initial toxicity testing was conducted to determine the concentrations to use in the 2 subsequent tests. In the first mutagenicity test conducted by the Direct Plate Incorporation method, the concentrations used were 16.6, 49.8, 166, 498, 1659 and 4978 μg per plate while in the second mutagenicity test conducted by the Pre-incubation method, concentrations of 17, 50, 167, 500, 1667 and 5000 μg- per plate were used. Triplicate plates were used at each exposure level.
In the initial toxicity test, no toxicity to the bacteria was observed at any concentration in either the absence or the presence of S9 mix and no precipitation of HB TMP was observed at any tested concentration. In the subsequent mutation tests, in the direct plate incorporation method, no toxicity to the bacteria was observed at any concentration of HB TMP. In the second test, conducted by the Pre-incubation Method, toxicity to all 5 strains was observed as a slight thinning of the background lawn of microcolonies. This observation was made at the highest concentration of 5000 μg per plate, only in the absence of S9 mix. No precipitation of HB TMP was observed at any concentration in either mutation test.
Under the conditions of this study, HB TMP is not considered mutagenic when tested on Salmonella typhimurium and Escherichia coli in the presence and absence of metabolic activation at concentrations up to the predetermined maximum of 5000 μg per plate. Consequently, HB TMP does not require classification according to CLP.
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