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EC number: 203-518-7 | CAS number: 107-75-5
- 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 mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Aug 2017 - May 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test using the Hprt and xprt genes)
- Version / remarks:
- Jul 2016
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- May 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Version / remarks:
- Aug 1998
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht
- Type of assay:
- in vitro mammalian cell gene mutation test using the Hprt and xprt genes
Test material
- Reference substance name:
- 7-hydroxycitronellal
- EC Number:
- 203-518-7
- EC Name:
- 7-hydroxycitronellal
- Cas Number:
- 107-75-5
- Molecular formula:
- C10H20O2
- IUPAC Name:
- 7-hydroxy-3,7-dimethyloctanal
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source: BASF SE, Ludwigshafen, Germany
- Batch No.of test material: 00084577L0
- Purity: 99.4%
- Physical state, appearance: liquid, colorless, clear
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: guaranteed
- Homogeneity: guaranteed, ensured by mixing
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: weighed, topped up and dissolved in culture medium to achieve the required concentration. Achieving a solution, ultrasonic waves, shaking or pipetting thoroughly was used. Solutions were prepared immediately before administration.
OTHER SPECIFICS:
- measurement of pH (at least top concentrations and negative control), osmolality (at least top concentration and negative control), solubility, cell morphology, and precipitation
Method
- Target gene:
- X-linked hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- source of S9: rat liver induced phenobarbital and beta-naphthoflavone
- method of preparation of S9 mix: according to Ames et al. ( 1975)
- concentration or volume of S9 mix and S9 in the final culture medium: 1 part S9 fraction with 9 parts S9 supplement. S9 mix consisted of 10% S9 fraction. - Test concentrations with justification for top dose:
- 1st experiment: 400, 600, 800, 1000, 1200, 1400, 1600 µg/ml (without S9); 37.5, 75, 150, 300, 600, 800, 1200 µg/ml (with S9)
2nd experiment: 800, 1000, 1200, 1300, 1400, 1500, 1600, 1750 µg/ml (without S9); 200, 400, 800, 1000, 1200, 1300, 1500 µg/ml (with S9)
3rd experiment: 1000, 1200, 1300, 1400, 1500, 1600, 1750 µg/ml (without S9); 200, 400, 800, 1000, 1200, 1300, 1500 µg/ml (with S9)
4th experiment: 200, 400, 800, 1000, 1200, 1300, 1400, 1500, 1600 µg/ml (without S9)
5th experiment: 800, 1000, 1100, 1200, 1250, 1300, 1350, 1400, 1450, 1500 µg/ml (without S9)
The doses/concentrations tested in this study were selected in accordance with the requirements set forth in the test guidelines and based on the results of a preliminary range finding test. - Vehicle / solvent:
- - Vehicle used: culture medium (Ham's F12)
- Justification for choice of vehicle: Due to the good solubility of the test substance in water, culture medium (Ham's F12) was used as most suitable vehicle.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: single
- Number of independent experiments : 5
METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding: 20x10^6 cells in 40 ml
- Test substance added in medium
TREATMENT AND HARVEST SCHEDULE:
- Test substance incubation: 20-24 h after seeding
- Exposure duration/duration of treatment: 4 h
FOR GENE MUTATION:
- Expression time (cells in growth medium between treatment and selection): 7-9 days
- Selection time (if incubation with a selective agent): 6-7 days, seeded in 20 ml selection medium (Ham's F12 with 6-thioguanine (10 µg/ml) and 10% FCS)
- Fixation time: Fixed with methanol, stained with Giemsa
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: relative survival (RS), cloning efficiency
METHODS FOR MEASUREMENTS OF GENOTOXICIY
- Method: mutant frequency
- OTHER:
In the 2nd Experiment strong precipitation occurred from 1200.0 μg/mL onward with and without S9 mix while no precipitation could be observed in the pre-test and in the 1st Experiment. Due to this discrepancy, the 2nd Experiment was discontinued and is not reported. This experimental part was repeated in Experiment 3.
In the 3rd Experiment after 4 hours treatment in the absence of metabolic activation strong cytotoxicity occurred at 1300.0 μg/mL and above. Thus, with only two remaining test groups this experimental part of the study did not fulfill the recommendations of the current OECD Guideline 476 and is not reported. This experimental part was repeated in Experiment 4. The results of the experiments 1 and 4 in the absence of metabolic activation were reassessed in an additional experiment (5th Experiment). - Evaluation criteria:
- A test substance is considered to be clearly positive if all following criteria are met:
• A statistically significant increase in mutant frequencies is obtained.
• A dose-related increase in mutant frequencies is observed.
• The corrected mutation frequencies (MFcorr.) exceeds both the concurrent negative control value and the range of our laboratory’s historical negative control data (95% control limit)
Isolated increases of mutant frequencies above our historical negative control range or isolated statistically significant increases without a dose-response relationship may indicate a biological effect but are not regarded as sufficient evidence of mutagenicity.
A test substance is considered to be clearly negative if the following criteria are met:
• Neither a statistically significant nor dose-related increase in the corrected mutation frequencies is observed under any experimental condition.
• The corrected mutation frequencies in all treated test groups is close to the concurrent vehicle control value and within the range of our laboratory’s historical negative control data (95% control limit) - Statistics:
- Trend test (MS Excel function RGP) assessing possible dose-related increase of mutant frequencies. Statistical significance was judged if trend was below probability value (p value) of 0.05 and slope was greater than 0.
Pair-wise comparison was carried out using one-sided Fisher's exact test with Bonferroni-Holm correction. The calculation was performed using R.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Remarks:
- At 1300 µg/ml a statistically increase in mutant frequency was observed but was considered as biologically irrelevant, because the value was well within the historical negative control data range
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- At 1200 µg/ml and above
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- At 1100 µg/ml and above
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- True negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Data on pH: Not influenced by test substance treatment
- Data on osmolality: Not influenced by test substance treatment
- Precipitation: no precipitation was observed
- Cell morphology: cell morphology and attachment of cells not adversely influenced, except in experiments 4 and 5 after 4 h in the absence of metabolic activation in at least the highest applied concentration where cells were adversely influenced
RESULTS OF MAIN STUDY:
- Summary table of results obtained in the study were attached to dossier.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation, and 95% control limits for the distribution as well as the number of data)
- Positive historical control data: range 42.47 - 419.90 (without S9, EMS), mean 158.01, SD 80.87, 95% control limits 0.00 (lower) and 320.94 (upper); range 21.52 - 270.48 (with S9, DMBA), mean 125.89, SD 56.16, 95% control limits 13.02 (lower) and 238.77 (upper)
- Negative historical control data: range 0.00 - 7.09 (without S9), mean 2.86, SD 1.81, 95% control limits 0.00 (lower) and 6.49 (upper); range 0.00 - 9.93 (with S9), mean 2.93, SD 2.24, 95% control limits 0.00 (lower) and 7.43 (upper)
Applicant's summary and conclusion
- Conclusions:
- Thus, the conclusion is drawn that in the absence of metabolic activation, the test substance induces gene mutations in the HPRT locus assay using CHO cells under the experimental conditions chosen.
- Executive summary:
The test substance was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro. Five independent experiments were carried out, with and without the addition of liver S9 mix from phenobarbital- and β-naphthoflavone induced rats (exogenous metabolic activation).
According to an initial range-finding cytotoxicity test for the determination of the experimental doses and taking into account the cytotoxicity actually found in the main experiments, the following concentrations were tested, whereby the highest tested concentration. Test groups printed in bold type were evaluated for gene mutations:
1st Experiment
without S9 mix
0; 400.0; 600.0; 800.0; 1000.0; 1200.0; 1400.0; 1600.0 μg/mL
with S9 mix
0; 37.5; 75.0; 150.0; 300.0; 600.0; 800.0; 1200.0 μg/mL
2nd Experiment (not valid; data not shown)
without S9 mix
0; 800.0; 1000.0; 1200.0; 1300.0; 1400.0; 1500.0; 1600.0; 1750.0 μg/mL
with S9 mix
0; 200.0; 400.0; 800.0; 1000.0; 1200.0; 1300.0; 1500.0 μg/mL
3rd Experiment
without S9 mix (did not fulfil the recommendations of the OECD Guideline 476; data
not shown)
0; 1000.0; 1200.0; 1300.0; 1400.0; 1500.0; 1600.0; 1750.0 μg/mL
with S9 mix
0; 200.0; 400.0; 800.0; 1000.0; 1200.0; 1300.0; 1500.0 μg/mL
4th Experiment
without S9 mix
0; 200.0; 400.0; 800.0; 1000.0; 1200.0; 1300.0; 1400.0; 1500.0; 1600.0 μg/mL
5th Experiment
without S9 mix
0; 800.0; 1000.0; 1100.0; 1200.0; 1250.0; 1300.0; 1350.0; 1400.0; 1450.0; 1500.0 μg/mL
Following attachment of the cells for 20 - 24 hours, cells were treated with the test substance for 4 hours in the absence and presence of metabolic activation. Subsequently, cells were cultured for 6 - 8 days and then selected in 6-thioguanine-containing medium for another week.
Finally, the colonies of each test group were fixed with methanol, stained with Giemsa and counted.
The vehicle controls gave mutant frequencies within the range expected for the CHO cell line.
Both positive control substances, ethyl methanesulfonate (EMS) and 7,12-dimethylbenz[a]-
anthracene (DMBA), led to the expected statistically significant increase in the frequencies of
forward mutations.
In this study, in all experimental parts, at least the highest concentrations evaluated for gene mutations were clearly cytotoxic in the absence and the presence of metabolic activation.
Based on the results of the present study, the test substance caused a statistically significant increase in the mutant frequencies in the absence of metabolic activation in all experiments.
Thus, under the experimental conditions of this study, the test substance is considered to induce forward mutations in the HPRT locus assay under in vitro conditions in CHO cells in the absence of metabolic activation.
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