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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 627-199-2 | CAS number: 120728-10-1
- 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:
- 2015-12-14 to 2015-12-21
- 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)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 1-[(tert-butoxycarbonyl)amino]cyclobutane-1-carboxylic acid
- EC Number:
- 627-199-2
- Cas Number:
- 120728-10-1
- Molecular formula:
- C10H17NO4
- IUPAC Name:
- 1-[(tert-butoxycarbonyl)amino]cyclobutane-1-carboxylic acid
- Test material form:
- solid: particulate/powder
- Details on test material:
- Physical state: powder
Appearance: white powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: M15BD0548
- Expiration date of the lot/batch: 2017-01-30 (retest date)
- Purity test date: 2015-01-31
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature, dessicated
- Solubility and stability of the test substance in the solvent/vehicle: not indicated
OTHER SPECIFICS: A correction factor of 1.06 for the purity/composition of the test item was applied in this study.
Method
- Target gene:
- histidine locus (histidine-dependent S. typhimurium strains)
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix (Aroclor 1254 induced rat liver metabolic activation system).
- Test concentrations with justification for top dose:
- Dose-range finding test: 1.6, 5.1, 16, 49, 155, 483, 1509 and 4717 µg/plate with and without 5% S9-mix (TA100).
Mutation experiment I: 49, 155, 483, 1509 and 4717 µg/plate with and without 5% S9-mix (TA1535, TA1537, TA98 and TA102).
Mutation experiment II: 492, 878, 1568, 2800 and 5000 µg/plate with and without 10% S9-mix (all tester strains).
Mutation experiment III: 2500 and 5000 µg/plate with and without 5% S9-mix (all tester strains).
Since the test item was soluble in DMSO at 47.17 mg/ml (=4717 µg/plate), this was selected as the highest dose level for the dose range finding test. Based on the results of the dose range finding test, 4717 and 5000 µg/plate were selected as the highest dose levels for the mutation experiments. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO.
- Justification for choice of solvent/vehicle: The test item was observed to be insoluble in water at 47.17 mg/ml. In DMSO, the test item was soluble at 47.17 mg/ml (= 4717 µg/plate). Based on these solubility findings, DMSO was selected as vehicle and 4717 µg/plate was selected as the maximum final concentration for the dose range finding test.
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- Without metabolic activation; 5 μg/plate (TA1535)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ICR-191
- Remarks:
- Without metabolic activation; 2.5 μg/plate (TA1537)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Without metabolic activation; 10 μg/plate (TA98)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- Without metabolic activation; 650 μg/plate (TA100)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: tert-butyl hydroperoxide
- Remarks:
- Without metabolic activation; 250 μg/plate (TA102)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- With S9-mix; 2.5μg/plate (TA1535 with 5 and 10% S9-mix, TA1537 with 5% S9-mix), 5μg/plate (TA1537 with 10% S9-mix), 1μg/plate (TA98 with 5 and 10% S9-mix, TA100 with 5% S9-mix), 2μg/plate (TA100 with 10% S9-mix), 10μg/plate (TA102 with 5 and 10% S9-mix)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation):
Top agar in top agar tubes was melted by heating to 45 ± 2°C. The following solutions were successively added to 3 ml molten top agar: 0.1 ml of a fresh bacterial culture (109 cells/ml) of one of the tester strains, 0.1 ml of a dilution of the test item in DMSO and either 0.5 ml S9-mix (in case of activation assays) or 0.5 ml 0.1 M phosphate buffer (in case of non-activation assays). The ingredients were mixed on a Vortex and the content of the top agar tube was poured onto a selective agar plate. After solidification of the top agar, the plates were inverted and incubated in the dark at 37.0 ± 1.0 °C for 48 ± 4 h. After this period revertant colonies were counted.
DURATION
- Exposure duration: 48+-4h
- Selection time (if incubation with a selection agent): 48+-4h (simultaneous with exposure)
SELECTION AGENT (mutation assays): histidine
NUMBER OF REPLICATIONS: triplicate
DETERMINATION OF CYTOTOXICITY
- Method: the reduction of the bacterial background lawn, the increase in the size of the microcolonies and/or the reduction of the revertant colonies - Evaluation criteria:
- A test item is considered negative (not mutagenic) in the test if:
a) The total number of revertants in the tester strain TA100 or TA102 is not greater than two (2) times the concurrent control, and the total number of revertants in tester strains TA1535, TA1537 or TA98 is not greater than three (3) times the concurrent vehicle control.
b) The negative response should be reproducible in at least one follow-up experiment.
A test item is considered positive (mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 or TA102 is greater than two (2) times the concurrent control, or the total number of revertants in tester strain TA1535, TA1537 or TA98 is greater than three (3) times the concurrent control.
b) A concentration related effect is observed.
c) In case a follow up experiment is performed when a positive response is observed in one of the tester strains, the positive response should be reproducible in at least one follow up experiment. - Statistics:
- No formal hypothesis testing was done.
In addition to the criteria stated below, any increase in the total number of revertants was evaluated for its biological relevance including a comparison of the results with the historical control data range.
Results and discussion
Test results
- Key result
- Species / strain:
- S. typhimurium, other: TA 1535, TA1537, TA98, TA100 and TA102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 4717 µg/plate in TA102 without S9-mix (experiment 1); at 5000 µg/plate in TA1535 without S9-mix (experiment 3)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test item was observed to be insoluble in water at 47.17 mg/ml.
- Precipitation: Precipitation of the test item on the plates was not observed at the start or at the end of the incubation period.
RANGE-FINDING/SCREENING STUDIES: Selection of an adequate range of doses was based on a dose range finding test with tester strain TA100 with and without 5% (v/v) S9-mix. Eight concentrations, 1.6, 5.1, 16, 49, 155, 483, 1509 and 4717 µg/plate were tested in triplicate. The highest concentration of the test item used in the subsequent mutation experiment was 4717 µg/plate. No increase in the number of revertants was observed upon treatment with the test item under all conditions tested. Precipitation of the test item on the plates was not observed at the start or at the end of the incubation period in any tester strain. No cytotoxicity was observed in any tester strain, except for TA102, where a slight reduction in the number of revertanst was observed (absence of S9-mix). Based on the results of the dose range finding test, the following dose range was selected for the first mutation experiment with the tester strains, TA1535, TA1537, TA98 and TA102 in the absence and presence of S9-mix: 49, 155, 483, 1509 and 4717 μg/plate.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: The strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly, except the responses for TA102 (absence of S9-mix, second and third experiment; presence of S9-mix, first experiment) . The purpose of the positive control is as a reference for the test system, where a positive response is required to check if the test system functions correctly. Since the values were 5.7 times greater in the presence of S9-mix and 1.7 to 2.1 times greater in the absence of S9-mix than the concurrent solvent control values, this deviation in the mean plate count of the positive control had no effect on the validity of the test results
- Negative (solvent/vehicle) historical control data: The negative control values were within the laboratory historical control data ranges, except the response for TA100 in the first experiment. Since the mean number of revertant colonies showed a slightly lower number of revertant colonies (54 and 65 revertant colonies in the absence and presence of S9-mix, respectively) when compared against relevant historical control data (64 and 70 relevant colonies in the absence and presence of S9-mix, respectively), the validity of the test was considered to be not affected.
Any other information on results incl. tables
Mutation experiment 2
Toxicity: In strain TA100 (absence and presence of S9-mix), fluctuations in the number of revertant colonies below the laboratory historical control data range were observed. However, since no dose-relationship was observed and the reductions were less than 20% compared to the concurrent vehicle control, these reduction are not considered to be caused by toxicity of the test item, and rather it is more likely these reductions are caused by an incidental fluctuation in the number of revertant colonies.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: negative with and without metabolic activation
Based on the results of this study it is concluded that the test item is not mutagenic in the Salmonella typhimurium reverse mutation assay.
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.