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EC number: 207-889-6 | CAS number: 499-75-2
- 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:
- 14 February 2017-23 May 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Carvacrol
- EC Number:
- 207-889-6
- EC Name:
- Carvacrol
- Cas Number:
- 499-75-2
- Molecular formula:
- C10H14O
- IUPAC Name:
- 2-methyl-5-(propan-2-yl)phenol
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Wanxiang International Flavors & Fragrances Pte., Ltd.; 2016111001
- Expiration date of the lot/batch:10 November 2018
- Purity test date:10-11-2016
- Purity: 99.91%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Refrigerated (2-8C), protected from light and humidity
Method
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/β- naphthoflavone-induced rat liver S9
- Test concentrations with justification for top dose:
- Preliminary toxicity test: 5000; 2500; 1000; 316; 100, 31.6, 10 μg/plate
Main test (1): 5000, 1581, 500, 158.1, 50, 15.81, 5 and 1.581 μg/plate
Main test (2): 5000, 1581, 500, 158.1, 50, 15.81, 5, 1.581 and 0.5 μg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle:The solubility of the test item was examined using Distilled water, Dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF). The test item was insoluble in Distilled water at 100 mg/ml concentration. The test item was soluble at this concentration using DMSO, DMF (clear solution was detected in both cases). Based on the results, DMSO was selected as vehicle (solvent) for the study.
Controls
- Untreated negative controls:
- yes
- Remarks:
- Untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- methylmethanesulfonate
- Remarks:
- TA98: 4-nitro-1,2-phenylenediamine (NPD) without activation; All strains: 2-aminoanthracene (2AA) with activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Preliminary Concentration Range Finding Test as well as in the Initial Mutation Test, the plate incorporation method was used. In the Confirmatory Mutation Test, the pre-incubation method was used.
DURATION
- Preincubation period: 20min at 37ºC
- Exposure duration: 48±1 hours
NUMBER OF REPLICATIONS: Triplicate.
DETERMINATION OF CYTOTOXICITY
- Method: Reduction in background lawn - Evaluation criteria:
- Criteria for Validity:
The study was considered valid if:
- the number of revertant colonies of the negative (solvent) and positive controls were in the historical control range in all strains of the main tests;
- at least five analyzable concentrations were presented in all strains of the main tests.
Criteria for a Positive Response:
A test item was considered mutagenic if:
- a dose–related increase in the number of revertants occurred and/or;
- a reproducible biologically relevant positive response for at least one of the dose groups occurred in at least one strain with or without metabolic activation.
An increase was considered biologically relevant if:
- the number of reversions was more than two times higher than the reversion rate of the negative (solvent) control in Salmonella typhimurium TA98, TA100 and
Escherichia coli WP2 uvrA bacterial strains;
- the number of reversions was more than three times higher than the reversion rate of the negative (solvent) control in Salmonella typhimurium TA1535 and
TA1537 bacterial strains.
Criteria for a Negative Response:
The test item was considered to have shown no mutagenic activity in this study 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. - Statistics:
- According to the guidelines, statistical method may be used as an aid in evaluating the test results. However, statistical significance should not be the only
determining factor for a positive response.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- other: All strains
- Remarks:
- Main test (1)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- >500 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- other: All strains
- Remarks:
- Main test (2)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 158.1 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitate was detected on the plates in the main tests in all examined strains with and without metabolic activation at higher concentrations.
RANGE-FINDING/SCREENING STUDIES:
In the Preliminary Concentration Range Finding Test (Informatory Toxicity Test), the plate incorporation method was used. This test was performed using Salmonella typhimurium TA98 and TA100 strains in the presence and absence of metabolic activation system (±S9 mix) with appropriate untreated, negative (vehicle/solvent) and positive controls. In the test, each sample (including the controls) was tested in triplicate.
Concentrations of 5000, 2500, 1000, 316, 100, 31.6 and 10 μg/plate were examined in the Preliminary Concentration Range Finding Test.
In the preliminary experiment, the numbers of revertant colonies were mostly in the normal range (minor differences were detected in some sporadic cases, but they were without biological significance and considered as biological variability of the test system).
No precipitate of the test item was detected in the Preliminary Range Finding Test. Inhibitory, cytotoxic effect of the test item (absent, reduced and sligtly reduced background lawn development, pinpoint colonies) was detected in the Preliminary Concentration Range Finding Test in Salmonella typhimurium TA98, TA100 strains at 5000, 2500 and 1000 μg/plate concentrations with and without metabolic
activation. The experimental results (revertant colony numbers per plate, mutation factors and standard deviations) are detailed in Table 7 (Appendix 2) and in Appendix 3.
HISTORICAL CONTROL DATA
- Positive historical control data: Yes with ranges, means and standard deviation (Period of 2011-2015) Appendix 6
- Negative (solvent/vehicle) historical control data: Yes with ranges, means and standard deviation (Period of 2011-2015) Appendix 6
Applicant's summary and conclusion
- Conclusions:
- The test item CARVACROL had no mutagenic activity in the applied bacterium tester strains under the test conditions used in this study.
- Executive summary:
In a reverse gene mutation assay in bacteria (16_399-007M), strains of S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvr A were exposed to Carvacrol (99.91%) in DMSO at concentrations of 5000, 1581, 500, 158.1, 50, 15.81, 5, 1.581 and 0 μg/plate (direct plate incorporation; experiment 1) and 5000, 1581, 500, 158.1, 50, 15.81, 5, 1.581, 0.5 and 0 μg/plate (20 minute pre-incubation; experiment 2) in the presence and absence of mammalian metabolic activation (Phenobarbital/β- naphthoflavone-induced rat liver S9).
Carvacrol was tested up to the limit concentration (5000 µg/plate). The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.
This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.
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