Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 214-222-2 | CAS number: 1115-20-4
- 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:
- Jan 10, 2023 - Jan 26, 2023
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 023
- Report date:
- 2023
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 26 Jun 2020
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 30 May 2008
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Version / remarks:
- Aug 1998
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Landesamt für Umwelt, Rheinland Pfalz, Germany
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 3-hydroxy-2,2-dimethylpropyl 3-hydroxy-2,2-dimethylpropionate
- EC Number:
- 214-222-2
- EC Name:
- 3-hydroxy-2,2-dimethylpropyl 3-hydroxy-2,2-dimethylpropionate
- Cas Number:
- 1115-20-4
- Molecular formula:
- C10H20O4
- IUPAC Name:
- 3-hydroxy-2,2-dimethylpropyl 3-hydroxy-2,2-dimethylpropanoate
- Details on test material:
- - Name of test material (as cited in study report): Hydroxypivalic acid neopentylglycol ester
- Batch identification: 09129047G0
- Purity: 99.6 %
- Homogeneity: The homogeneity of the test substance was ensured by mixing before preparation of the test substance preparations.
- Stability under test conditions: The stability of the test substance under storage conditions was guaranteed until 04 Apr 2024 as indicated by the sponsor and the sponsor holds this responsibility.The test facility is organizationally independent from the BASF SE sponsor division.
- Date of production: 05 Apr 2022
- Physical state, appearance: solid, white
- Storage conditions: room temperature
Constituent 1
Method
- Target gene:
- his, trp
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:
- Type and composition of metabolic activation system: rat liver S9-mix
- Source of S9: male Wistar rats i.p. injected with 80 mg/kg b.w. phenobarbital and ß-naphthoflavone orally each on three consecutive days; 24 h after the last administration rats were sacrificed and liver S9-fraction prepared
- Method of preparation of S9 mix: was prepared freshly prior to each experiment; a sufficient amount of S9 fraction was thawed at room temperature and 1 part of S9 fraction is mixed with 9 parts of S9 supplement (cofactors: MgCl2 8mM, KCl 33 mM, glucose-6-phosphate 5 mM, NADP 4 mM, phosphate buffer pH 7.4 15mM); mixture of both components (S9 mix) was kept on ice until used
- Concentration or volume of S9 mix and S9 in the final culture medium
- Quality controls of S9: sterility of the S9 fraction was assessed and confirmed; to demonstrate the efficacy of the S9 mix in this assay, the S9 batch was characterized with benzo(a)pyrene - Test concentrations with justification for top dose:
- 33 μg - 5000 μg/plate (SPT)
33 μg - 5000 μg/plate (PIT)
In agreement with the recommendations of current guidelines 5 mg/plate or 5 μL/plate is generally selected as maximum test dose at least in the 1st Experiment. However, this maximum dose can be tested even in the case of relatively insoluble test compounds to detect possible mutagenic impurities. Furthermore, doses > 5 mg/plate or > 5 μL/plate might also be tested in repeat experiments for further clarification/substantiation. In this study, 5 mg/plate could be used as top concentration. - Vehicle / solvent:
- Due to the good solubility of the test substance in water, ultrapure water was used as vehicle.
Controls
- 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
- other: 2-aminoanthracene (2-AA), N-methyl-N`-nitro-N-nitrosoguanidine (MNNG), 4-nitro-o-phenylenediamine (NOPD),
- Details on test system and experimental conditions:
- MUTAGENICITY TESTS
i) Standard plate test (3 test plates per dose or per control)
The experimental procedure of the standard plate test (plate incorporation method) was based on the method of Ames et al. (1975, 1983).
a) Salmonella typhimurium
Test tubes containing 2-mL portions of soft agar (overlay agar), which consists of 100 mL agar (0.8% [w/v] agar + 0.6% [w/v] NaCl) and 10 mL amino acid solution (minimal amino acid solution for the determination of mutants: 0.5 mM histidine + 0.5 mM biotin) were kept in a water bath at about 42 - 45°C, and the remaining components were added in the following order: 0.1 mL test solution, vehicle or positive control, 0.1 mL fresh bacterial culture, 0.5 mL S9 mix (with external metabolic activation) or 0.5 mL phosphate buffer (without external metabolic activation). After mixing, the samples were poured onto Minimal glucose agar plates within approx. 30 seconds. After incubation at 37°C (mean value ±2°C) for 48-72 h in the dark, the bacterial colonies (his+ revertants) were counted. The colonies were counted using the Sorcerer Image Analysis System with the software program Ames Study Manager. In several cases, colonies were counted manually, in particular, if precipitation of the test substance hindered the counting using the Image Analysis System.
b) Escherichia coli
Test tubes containing 2-mL portions of soft agar (overlay agar), which consists of 100 mL agar (0.8% [w/v] agar + 0.6% [w/v] NaCl) and 10 mL amino acid solution (minimal amino acid solution for the determination of mutants: 0.5 mM tryptophan) were kept in a water bath at about 42 - 45°C, and the remaining components were added in the following order: 0.1 mL test solution, vehicle or positive control, 0.1 mL fresh bacterial culture, 0.5 mL S9 mix (with external metabolic activation) or 0.5 mL phosphate buffer (without external metabolic activation). After mixing, the samples were poured onto Minimal glucose agar plates within approx. 30 sec. After incubation at 37°C (mean value ±2°C) for 48-72 h in the dark, the bacterial colonies (trp+ revertants) were counted. The colonies were counted using the Sorcerer Image Analysis System with the software program Ames Study Manager. In several cases, colonies were counted manually, in particular, if precipitation of the test substance hindered the counting using the Image Analysis System.
ii) Preincubation test (3 test plates per dose or per control)
The experimental procedure was based on the method described by Yahagi et al. (1977) and Matsushima et al. (1980). 0.1 mL test solution, vehicle or positive control, 0.1 mL bacterial suspension and 0.5 mL S9 mix (with external metabolic activation) or phosphate buffer (without external metabolic activation) were incubated at 37°C for the duration of about 20 minutes using a shaker. Subsequently, 2 mL of soft agar was added and, after mixing, the samples were poured onto the agar plates within approx. 30 seconds. After incubation at 37°C (mean value ±2°C) for 48-72 h in the dark, the bacterial colonies were counted. The colonies were counted using the Sorcerer Image Analysis System with the software program Ames Study Manager. In several cases, colonies were counted manually, in particular, if precipitation of the test substance hindered the counting using the Image Analysis System.
EVALUATION OF TOXICITY
Toxicity defined by a decrease in the number of revertants (factor ≤ 0.6) and clearing or diminution of the background lawn (= reduced his- or trp- background growth) was investigated for all test groups both with and without S9 mix in all experiments. Single values with a factor ≤ 0.6 are not detected as toxicity in low dose groups.
EVALUATION OF SOLUBILTY
If precipitation of the test material is observed, it is recorded. As long as precipitation do not interfere with the colony scoring, 5 mg/plate is generally selected and analyzed (in cases of nontoxic compounds) as the maximum dose at least in the 1st Experiment even in the case of relatively insoluble test compounds to detect possible mutagenic impurities. Furthermore, doses > 5 mg/plate might also be tested in repeat experiments for further clarification/substantiation.
ACCEPTANCE CRITERIA
Generally, the experiment is considered valid if the following criteria are met:
- The number of revertant colonies in the negative controls are within the range of the historical negative control data for each tester strain. If a value is not within the control range, the value might be accepted if it is not a clear outlier and there is evidence that the test system is “under control” and there is evidence of no technical or human failure
- The sterility controls reveal no indication of bacterial contamination. Test substance precipitation should not interfere with the scoring.
- The positive control substances both with and without S9 mix induce a distinct increase in the number of revertant colonies compatible with the range of the historical positive control data or above
- Fresh bacterial culture containing approximately 109 cells per mL are used. - Rationale for test conditions:
- In agreement with the recommendations of current guidelines.
- Evaluation criteria:
- The test substance is considered positive in this assay if the following criteria are met:
- A dose-related and reproducible increase in the number of revertant colonies, i.e. at least doubling (bacteria strains with high spontaneous mutation rate, like TA 98, TA 100 and E.coli WP2 uvrA) or tripling (bacteria strains with low spontaneous mutation rate, like TA 1535 and TA 1537) of the spontaneous mutation rate in at least one tester strain either without S9 mix or after adding a metabolizing system.
A test substance is generally considered non-mutagenic in this test if:
- The number of revertants for all tester strains are within the range of the historical negative control data under all experimental conditions in at least two experiments carried out independently of each other. - Statistics:
- not specified
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- only in the PIT with S9 mix at 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- 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
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- 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
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- only in the SPT with S9 mix at 2500 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- only in the PIT with S9 mix at 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
No test substance precipitation was observed with and without S9 mix.
The additional treated plates for sterility control showed no contamination in all performed experiments.
STUDY RESULTS
No relevant increase in the number of his+ or trp+ revertants with and without S9 mix in all strains tested (see tables 1-4).
A bacteriotoxic effect (slight decrease in the number of his+ revertants) was observed in the standard plate test depending on the strain and test conditions at 2500 μg/plate. In the preincubation assay bacteriotoxicity (slight decrease in the number of his+ or trp+ revertants) was occasionally observed depending on the strain and test conditions at 5000 μg/plate.
HISTORICAL CONTROL DATA
see tables 5-8
Any other information on results incl. tables
Table 1: Mutagenicity without metabolic activation - SPT
Strain | Test group | Dose (µg/plate) | Mean revertants per plate | Standard deviation | Factor | Individual revertant colony counts |
TA 1535 | Water | - | 16.3 | 0.6 | - | 16, 16, 17 |
Test Item | 33 | 15.3 | 6.5 | 0.9 | 15, 22 ,9 | |
| 100 | 17.0 | 1.0 | 1.0 | 17, 16, 18 | |
| 333 | 20.3 | 2.5 | 1.2 | 18, 20, 23 | |
| 1000 | 16.7 | 3.5 | 1.0 | 13, 17, 20 | |
| 2500 | 11.3 | 3.2 | 0.7 | 10, 9, 15 | |
| 5000 | 12.0 | 5.0 | 0.7 | 12, 17, 7 | |
MNNG | 5.0 | 2356.3 | 434.5 | 144.3 | 2432, 2748, 1889 | |
TA 100 | Water | - | 135.7 | 16.3 | - | 117, 143, 147 |
Test Item | 33 | 129.0 | 10.5 | 1.0 | 119, 140, 128 | |
| 100 | 143.3 | 7.5 | 1.1 | 136, 151, 143 | |
| 333 | 136.0 | 14.7 | 1.0 | 128, 153, 127 | |
| 1000 | 133.3 | 6.4 | 1.0 | 138, 126, 136 | |
| 2500 | 147.3 | 10.5 | 1.1 | 147, 137, 158 | |
| 5000 | 146.0 | 1.0 | 1.1 | 146, 145, 147 | |
MNNG | 5.0 | 2243.0 | 421.2 | 16.5 | 2657, 2257, 1815 | |
TA 1537 | Water | - | 11.3 | 3.1 | - | 8, 14, 12 |
Test Item | 33 | 11.0 | 4.4 | 1.0 | 9, 16, 8 | |
| 100 | 11.7 | 7.6 | 1.0 | 17, 15, 3 | |
| 333 | 13.3 | 4.2 | 1.2 | 12, 18, 10 | |
| 1000 | 8.3 | 3.2 | 0.7 | 12, 7, 6 | |
| 2500 | 10.7 | 5.0 | 0.9 | 16, 6, 10 | |
| 5000 | 13.0 | 7.0 | 1.1 | 21, 10, 8 | |
AAC | 100 | 1005.3 | 240.0 | 88.7 | 775, 987, 1254 | |
TA 98 | Water | - | 17.7 | 2.1 | - | 16, 17, 20 |
Test Item | 33 | 26.3 | 5.5 | 1.5 | 30, 29, 20 | |
| 100 | 17.7 | 4.2 | 1.0 | 21, 13, 19 | |
| 333 | 17.3 | 6.0 | 1.0 | 23, 11, 18 | |
| 1000 | 13.7 | 5.7 | 0.8 | 20, 9, 12 | |
| 2500 | 20.0 | 4.6 | 1.1 | 19, 25, 16 | |
| 5000 | 25.7 | 1.5 | 1.5 | 24, 26, 27 | |
NOPD | 10 | 469.3 | 109.3 | 26.6 | 595, 417, 396 | |
E. coli | Water | - | 26.7 | 3.2 | - | 23, 29, 28 |
Test Item | 33 | 18.3 | 2.9 | 0.7 | 20, 15, 20 | |
| 100 | 25.7 | 5.5 | 1.0 | 32, 22, 23 | |
| 333 | 25.7 | 0.6 | 1.0 | 25, 26, 26 | |
| 1000 | 24.0 | 2.6 | 0.9 | 21, 25, 26 | |
| 2500 | 27.0 | 3.6 | 1.0 | 24, 31, 26 | |
| 5000 | 20.3 | 5.5 | 0.8 | 15, 26, 20 | |
4-NQO | 5 | 1011.0 | 41.2 | 37.9 | 1041, 964, 1028 |
Table 2: Mutagenicity with metabolic activation - SPT
Strain | Test group | Dose (µg/plate) | Mean revertants per plate | Standard deviation | Factor | Individual revertant colony counts |
TA 1535 | Water | - | 11.3 | 1.5 | - | 11, 10, 13 |
Test Item | 33 | 8.3 | 2.9 | 0.7 | 10, 10, 5 | |
| 100 | 14.3 | 2.1 | 1.3 | 12, 15, 16 | |
| 333 | 11.3 | 4.2 | 1.0 | 8, 16, 10 | |
| 1000 | 10.7 | 2.5 | 0.9 | 13, 11,8 | |
| 2500 | 8.7 | 6.0 | 0.8 | 8, 15, 3 | |
| 5000 | 10.7 | 0.6 | 0.9 | 11, 10, 11 | |
MNNG | 5.0 | 162.0 | 14.8 | 14.3 | 179, 152, 155 | |
TA 100 | Water | - | 133.0 | 5.3 | - | 131, 139, 129 |
Test Item | 33 | 129.3 | 7.1 | 1.0 | 123, 128, 137 | |
| 100 | 131.7 | 21.1 | 1.0 | 118, 121, 156 | |
| 333 | 131.3 | 9.7 | 1.0 | 123, 129, 142 | |
| 1000 | 137.0 | 4.0 | 1.0 | 133, 137, 141 | |
| 2500 | 122.7 | 3.1 | 0.9 | 120, 126, 122 | |
| 5000 | 122.3 | 17.8 | 0.9 | 138, 103, 126 | |
MNNG | 5.0 | 1426.0 | 122.6 | 10.7 | 1552, 1419, 1307 | |
TA 1537 | Water | - | 13.0 | 3.6 | - | 17, 10, 12 |
Test Item | 33 | 9.3 | 4.0 | 0.7 | 13, 10, 5 | |
| 100 | 12.7 | 2.5 | 1.0 | 10, 15, 13 | |
| 333 | 10.0 | 2.0 | 0.8 | 8, 12, 10 | |
| 1000 | 14.0 | 5.6 | 1.1 | 8, 15, 19 | |
| 2500 | 13.7 | 5.5 | 1.1 | 10, 11, 20 | |
| 5000 | 14.0 | 1.0 | 1.1 | 13, 15, 14 | |
AAC | 100 | 96.3 | 2.1 | 7.4 | 94, 97, 98 | |
TA 98 | Water | - | 25.3 | 3.8 | - | 21, 28, 27 |
Test Item | 33 | 23.3 | 4.0 | 0.9 | 21, 28, 21 | |
| 100 | 16.0 | 4.4 | 0.6 | 13, 21, 14 | |
| 333 | 25.0 | 4.4 | 1.0 | 20, 27, 28 | |
| 1000 | 24.0 | 4.4 | 0.9 | 26, 27, 19 | |
| 2500 | 13.7 | 2.1 | 0.5 | 16, 13, 12 | |
| 5000 | 20.0 | 3.5 | 0.8 | 24, 18, 18 | |
NOPD | 10 | 872.7 | 87.1 | 34.4 | 934, 911, 773 | |
E. coli | Water | - | 27.3 | 5.7 | - | 29, 21, 32 |
Test Item | 33 | 29.7 | 2.3 | 1.1 | 31, 31, 27 | |
| 100 | 29.3 | 3.5 | 1.1 | 26, 29, 33 | |
| 333 | 27.0 | 6.2 | 1.0 | 25, 22, 34 | |
| 1000 | 20.7 | 5.5 | 0.8 | 26, 15, 21 | |
| 2500 | 31.7 | 2.1 | 1.2 | 30, 31, 34 | |
| 5000 | 23.0 | 4.6 | 0.8 | 27, 24, 18 | |
4-NQO | 5 | 118.0 | 10.4 | 4.3 | 130, 111, 113 |
Table 3: Mutagenicity without metabolic activation - PIT
Strain | Test group | Dose (µg/plate) | Mean revertants per plate | Standard deviation | Factor | Individual revertant colony counts |
TA 1535 | Water | - | 13.0 | 1.0 | - | 13, 14, 12 |
Test Item | 33 | 7.7 | 0.6 | 0.6 | 8, 8, 7 | |
| 100 | 11.0 | 2.6 | 0.8 | 9, 14, 10 | |
| 333 | 14.3 | 2.3 | 1.1 | 13, 17, 13 | |
| 1000 | 10.7 | 3.8 | 0.8 | 9, 8, 15 | |
| 2500 | 9.0 | 1.0 | 0.7 | 9, 8, 10 | |
| 5000 | 12.3 | 2.1 | 0.9 | 14, 13, 10 | |
MNNG | 5.0 | 5219.7 | 289.6 | 401.5 | 5060, 5554, 5045 | |
TA 100 | Water | - | 127.7 | 19.6 | - | 144, 133, 106 |
Test Item | 33 | 120.3 | 7.5 | 0.9 | 116, 116, 129 | |
| 100 | 110.3 | 9.7 | 0.9 | 108, 121, 102 | |
| 333 | 123.7 | 13.5 | 1.0 | 137, 124, 110 | |
| 1000 | 123.0 | 10.4 | 1.0 | 117, 117, 135 | |
| 2500 | 120.3 | 10.7 | 0.69 | 108, 127, 126 | |
| 5000 | 113.7 | 5.9 | 0.9 | 107, 118, 116 | |
MNNG | 5.0 | 4176.0 | 395.8 | 32.7 | 4431, 4377, 3720 | |
TA 1537 | Water | - | 12.0 | 2.0 | - | 14, 12, 10 |
Test Item | 33 | 15.7 | 3.2 | 1.3 | 12, 18, 17 | |
| 100 | 12.7 | 4.9 | 1.1 | 15, 16, 7 | |
| 333 | 14.3 | 4.2 | 1.2 | 19, 11, 13 | |
| 1000 | 9.7 | 1.2 | 0.8 | 11, 9, 9 | |
| 2500 | 12.7 | 5.8 | 1.1 | 16, 16, 6 | |
| 5000 | 8.3 | 3.1 | 0.7 | 11, 5, 9 | |
AAC | 100 | 1249.7 | 371.3 | 104.1 | 1174, 922, 1653 | |
TA 98 | Water | - | 27.0 | 6.6 | - | 34, 21, 26 |
Test Item | 33 | 19.7 | 8.1 | 0.7 | 14, 16, 29 | |
| 100 | 20.3 | 6.7 | 0.8 | 13, 26, 22 | |
| 333 | 18.7 | 5.9 | 0.7 | 12, 21, 23 | |
| 1000 | 23.3 | 7.0 | 0.9 | 16, 24, 30 | |
| 2500 | 25.0 | 7.0 | 0.9 | 32, 25, 18 | |
| 5000 | 22.3 | 2.1 | 0.8 | 20, 23, 24 | |
NOPD | 10 | 395.7 | 35.1 | 14.7 | 359, 399, 429 | |
E. coli | Water | - | 26.7 | 1.2 | - | 26, 26, 28 |
Test Item | 33 | 28.7 | 3.5 | 1.1 | 25, 32, 29 | |
| 100 | 27.3 | 9.0 | 1.0 | 32, 17, 33 | |
| 333 | 25.0 | 3.6 | 0.9 | 29, 24, 22 | |
| 1000 | 24.7 | 6.0 | 0.9 | 24, 19, 31 | |
| 2500 | 18.0 | 6.1 | 0.7 | 15, 14, 25 | |
| 5000 | 17.7 | 1.5 | 0.7 | 16, 18, 19 | |
4-NQO | 5 | 962.3 | 6.4 | 36.1 | 967, 965, 955 |
Table 4: Mutagenicity with metabolic activation - PIT
Strain | Test group | Dose (µg/plate) | Mean revertants per plate | Standard deviation | Factor | Individual revertant colony counts |
TA 1535 | Water | - | 16.0 | 7.0 | - | 11, 24, 13 |
Test Item | 33 | 9.3 | 1.5 | 0.6 | 9, 11, 8 | |
| 100 | 10.7 | 0.6 | 0.7 | 11, 11, 10 | |
| 333 | 10.0 | 2.0 | 0.6 | 8, 10, 12 | |
| 1000 | 12.7 | 6.0 | 0.8 | 19, 12, 7 | |
| 2500 | 11.3 | 1.5 | 0.7 | 10, 13, 11 | |
| 5000 | 6.7 | 1.5 | 0.4 | 5, 7, 8 | |
MNNG | 5.0 | 203.7 | 24.0 | 12.7 | 194, 231, 186 | |
TA 100 | Water | - | 114.3 | 19.4 | - | 131, 93, 119 |
Test Item | 33 | 120.7 | 11.4 | 1.1 | 108, 124, 130 | |
| 100 | 118.7 | 1.5 | 1.0 | 119, 117, 120 | |
| 333 | 120.3 | 11.0 | 1.1 | 124, 108, 129 | |
| 1000 | 121.0 | 6.6 | 1.1 | 122, 127, 114 | |
| 2500 | 113.7 | 16.8 | 1.0 | 110, 99, 132 | |
| 5000 | 112.3 | 12.9 | 1.0 | 98, 123, 116 | |
MNNG | 5.0 | 1848.3 | 221.3 | 16.2 | 2102, 1695, 1748 | |
TA 1537 | Water | - | 12.0 | 3.6 | - | 11, 16, 9 |
Test Item | 33 | 13.3 | 4.2 | 1.1 | 18, 10, 12 | |
| 100 | 13.7 | 5.5 | 1.1 | 14, 19, 8 | |
| 333 | 12.3 | 2.1 | 1.0 | 14, 10, 13 | |
| 1000 | 11.7 | 0.6 | 1.0 | 12, 11, 12 | |
| 2500 | 12.7 | 3.1 | 1.1 | 12, 10, 16 | |
| 5000 | 11.7 | 3.2 | 1.0 | 8, 14, 13 | |
AAC | 100 | 141.0 | 19.1 | 11.8 | 129, 131, 163 | |
TA 98 | Water | - | 25.7 | 5.7 | - | 32, 21, 24 |
Test Item | 33 | 17.0 | 4.0 | 0.7 | 13, 17, 21 | |
| 100 | 26.3 | 2.1 | 1.0 | 28, 24, 27 | |
| 333 | 27.3 | 7.6 | 1.1 | 19, 29, 34 | |
| 1000 | 30.3 | 4.0 | 1.2 | 28, 35, 28 | |
| 2500 | 19.7 | 4.6 | 0.8 | 17, 17, 25 | |
| 5000 | 20.3 | 8.7 | 0.8 | 13, 18, 30 | |
NOPD | 10 | 1683.7 | 84.9 | 65.6 | 1718, 1587, 1746 | |
E. coli | Water | - | 26.7 | 6.8 | - | 19, 29, 32 |
Test Item | 33 | 29.0 | 4.0 | 1.1 | 25, 29, 33 | |
| 100 | 29.3 | 2.1 | 1.1 | 31, 27, 30 | |
| 333 | 30.7 | 5.9 | 1.2 | 24, 33, 35 | |
| 1000 | 28.0 | 3.6 | 1.1 | 29, 24, 31 | |
| 2500 | 24.7 | 4.5 | 0.9 | 29, 20, 25 | |
| 5000 | 15.3 | 6.7 | 0.6 | 23, 11, 12 | |
4-NQO | 5 | 171.7 | 48.4 | 6.4 | 117, 189, 209 |
Table 5: Historical Negative Controls - SPT
Strain | S9 mix | Vehicle | No. of plates | No. of values | Min | Max | Mean | SD |
TA 1535 | without | all | 324 | 131 | 6 | 23 | 14 | 3.0 |
with | all | 330 | 131 | 4 | 19 | 13 | 2.6 | |
TA 100 | without | all | 342 | 132 | 82 | 202 | 117 | 15.4 |
with | all | 363 | 132 | 81 | 201 | 116 | 15.7 | |
TA 1537 | without | all | 336 | 132 | 6 | 14 | 10 | 1.9 |
with | all | 339 | 132 | 6 | 16 | 10 | 1.9 | |
TA 98 | without | all | 324 | 132 | 12 | 28 | 20 | 3.3 |
with | all | 348 | 132 | 16 | 33 | 24 | 3.4 | |
E. coli | without | all | 309 | 132 | 14 | 47 | 31 | 5.4 |
with | all | 309 | 132 | 18 | 50 | 32 | 7.5 |
Table 6: Historical Positive Controls - SPT
Strain | S9 mix | Pos. con. | No. of plates | No. of values | Min | Max | Mean | SD |
TA 1535 | without | MNNG | 254 | 96 | 2152 | 7963 | 4519 | 1068.5 |
with | 2-AA | 255 | 96 | 76 | 470 | 217 | 66.8 | |
TA 100 | without | MNNG | 264 | 95 | 593 | 5718 | 3470 | 931.8 |
with | 2-AA | 264 | 95 | 348 | 4066 | 2156 | 725.8 | |
TA 1537 | without | AAc | 267 | 96 | 283 | 1653 | 1049 | 271.8 |
with | 1-AA | 264 | 96 | 49 | 361 | 169 | 61.6 | |
TA 98 | without | NOPD | 258 | 96 | 332 | 1060 | 516 | 111.3 |
with | 2-AA | 261 | 95 | 350 | 3004 | 1580 | 564.0 | |
E. coli | without | 4-NQO | 240 | 96 | 517 | 1902 | 1076 | 233.6 |
with | 2-AA | 237 | 96 | 96 | 233 | 158 | 32.7 |
Table 7: Historical Negative Controls - PIT
Strain | S9 mix | Vehicle | No. of plates | No. of values | Min | Max | Mean | SD |
TA 1535 | without | all | 276 | 102 | 8 | 24 | 13 | 2.7 |
with | all | 273 | 102 | 7 | 29 | 13 | 3.1 | |
TA 100 | without | all | 281 | 103 | 75 | 150 | 114 | 14.9 |
with | all | 282 | 103 | 75 | 143 | 110 | 13.6 | |
TA 1537 | without | all | 282 | 102 | 5 | 14 | 10 | 2.0 |
with | all | 279 | 102 | 5 | 17 | 10 | 2.0 | |
TA 98 | without | all | 294 | 102 | 13 | 42 | 21 | 3.6 |
with | all | 282 | 102 | 17 | 35 | 25 | 3.5 | |
E. coli | without | all | 273 | 102 | 19 | 46 | 31 | 5.7 |
with | all | 273 | 102 | 17 | 45 | 30 | 5.9 |
Table 8: Historical Positive Controls - PIT
Strain | S9 mix | Pos. con. | No. of plates | No. of values | Min | Max | Mean | SD |
TA 1535 | without | MNNG | 219 | 81 | 6651 | 5758 | 3273 | 800.3 |
with | 2-AA | 2179 | 81 | 58 | 329 | 168 | 63.8 | |
TA 100 | without | MNNG | 228 | 81 | 546 | 4583 | 2502 | 845.5 |
with | 2-AA | 225 | 81 | 263 | 4056 | 1458 | 893.5 | |
TA 1537 | without | AAc | 225 | 81 | 195 | 2240 | 944 | 315.6 |
with | 1-AA | 225 | 81 | 45 | 419 | 141 | 61.5 | |
TA 98 | without | NOPD | 234 | 81 | 376 | 797 | 526 | 88.2 |
with | 2-AA | 225 | 81 | 163 | 3105 | 1138 | 648.1 | |
E. coli | without | 4-NQO | 219 | 81 | 235 | 1574 | 634 | 364.0 |
with | 2-AA | 219 | 81 | 99 | 276 | 167 | 38.1 |
Applicant's summary and conclusion
- Conclusions:
- negative
- Executive summary:
In the GLP OECD471 study, hydroxypivalic acid neopentylglycol ester (HPN) was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay.
STRAINS: TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA
DOSE RANGE: 33 μg - 5000 μg/plate (SPT); 33 μg - 5000 μg/plate (PIT)
TEST CONDITIONS: Standard plate test (SPT) and preincubation test (PIT) both with and without external metabolic activation (liver S9 mix from rats treated with enzyme inducers).
SOLUBILITY: No precipitation of the test substance was observed with and without S9 mix.
TOXICITY: A bacteriotoxic effect was occasionally observed depending on the strain and test conditions at and above 2500 μg/plate
MUTAGENICITY: A relevant increase in the number of his+ or trp+ revertants (increased by a factor of 2 or above compared to the concurrent control for Salmonella typhimurium TA 100, TA 98 and Escherichia coli WP2 uvrA, or a factor of 3 or above for Salmonella typhimurium TA 1535 and TA 1537) was not observed in the standard plate test or in the preincubation test with or without the addition of an external metabolizing system (liver S9 mix of rats treated with enzyme inducers).
Under the experimental conditions of this study, the test substance Hydroxypivalic acid neopentylglycol ester is not mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay in the absence and the presence of external metabolic activation.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.