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EC number: 240-759-7 | CAS number: 16712-64-4
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1999-08-17 - 2000-02-07
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented GLP study performed in compliance with OECD 476
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- HPRT Locus
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- V79 cells supplied by Laboratory for Mutagenicity Testing, Technical University, D-64293 Darmstadt.
- Type and identity of media: MEM + 10% FCS
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Mammalian S9
- Test concentrations with justification for top dose:
- Experiment 1:
- Without S9: 62.5, 125.0, 250.0, 500.0, 1000.0 and 1500.0 microg/mL
- With S9: 125.0, 250.0, 500.0, 1000.0, 1500.0 and 2000.0 microg/mL
Experiment 2:
- Without S9: 62.5, 125.0, 250.0, 500.0, 750.0 and 1000.0 microg/mL - Vehicle / solvent:
- Vehicle selected was DMSO.
Vehicle was chosen based on test article solubility properties in vehicle and lack of toxicity to the V79 cells. - Untreated negative controls:
- yes
- Remarks:
- no treatement; cells in culture medium
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Remarks:
- EMS used for "-S9"; DMBA used for "+S9"
- Positive control substance:
- 7,12-dimethylbenzanthracene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium.
DURATION
- Preincubation period: No pre-incubation for treatments.
- Exposure duration: 4 hours for Experiment No. 1; 24 hours for Experiment No. 2
- Expression time (cells in growth medium): 7 days.
- Selection time (if incubation with a selection agent): 8 days, post-expression time.
- Fixation time (start of exposure up to fixation or harvest of cells): 16 - 17 days.
SELECTION AGENT (mutation assays): 6-thioguanine (6-TG)
STAIN (for cytogenetic assays): 10% methylene blue in 0.01 KOH Solution.
NUMBER OF REPLICATIONS: One replicate each (with two flasks per condition) for each experiment (4 hr/-S9; 4 hr/+S9; 24 hr/-S9)
NUMBER OF CELLS EVALUATED: 1.5 x10^6 cells seeded for mutation rate experiment; 5.0 x10^2 cells seeded for toxicity experiment.
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency. - Evaluation criteria:
- Acceptability of the Assay:
The assay was considered acceptable if:
A. The number of mutant colonies per 10^6 cells found in the negative and/or solvent controls falls within the laboratory's historical control data range.
B. The positive control substances produce a significant increase in mutant colony frequencies.
C. The cloning efficiency (absolute value) of the negative and/or solvent controls must exceed 50%.
A test article is considered mutagenic if it induces either a concentration-dependent increase of the mutant frequency, or a reproducible and positive response at one of the test points. Additionally, the increase must be 3X above the spontaneous mutation frequency at least at one concentration. If the increase is not 3X, then if the dose-dependent increase is reproducible, the test article may still be considered to be mutagenic, dependent on a comparison to the spontaneous mutation frequency.
A test article not producing either a concentration-dependent increase in the mutant frequency or a reproducible positive response at any of the test points is considered non-mutagenic. - Statistics:
- Since the distribution of mutant cells does not follow known statistical models, an adequate statistical method is not available.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cytotoxicity observed at highest doses.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitation was observed only in the pre-test toxicity experiment, and only at the top dose.
RANGE-FINDING/SCREENING STUDIES: Based on the pre-test toxicity experiment, the concentration ranges were selected to yield cytotoxic effects at the higher doses.
COMPARISON WITH HISTORICAL CONTROL DATA: All experimental results requiring comparison to historical values were within the limits of those historical values. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
In conclusion, it can be stated that during the described mutagenicity test, and under the experimental conditions reported, the test article did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, 6-hydroxy-2-naphthoic acid is considered to be non-mutagenic in this assay. - Executive summary:
The study was performed to investigate the potential of the test article to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The assay was performed in two independent experiments. The cells were exposed to the test article for 4 hours in the first experiment with and without metabolic activation (S9 mix). In the second experiment, cells were exposed to test article for 24 hours, and solely in the absence of metabolic activation.
In the main experiments, the following concentrations were evaluated:
Experiment 1
- without S9 mix: 125.0, 250.0, 500.0, 1000.0 and 1500.0 microg/mL
- with S9 mix: 125.0, 250.0, 500.0, 750.0 and 1000.0 microg/mL
Experiment 2
- without S9 mix: 125.0, 250.0, 500.0, and 1000.0 microg/mL
Visible precipitation of the test item only occurred in the pre-experiment at the highest concentration of test article (2000.0 microg/mL). Toxic effects occurred in the pre-experiment at 1000.0 microg/mL and above without metabolic activation (4h and 24h treatments), and at 2000.0 microg/mL with metabolic activation. Based on the results of the pre-test on toxicity, the concentrations were selected to yield concentration-related toxic effects. The highest concentration produced a low-level of survival, and the survival at the lowest concentration was relatively close to the negative control.
The concentration range of the test article was limited by toxicity. In the first experiment, strong toxic effects occurred at 1500.0 microg/mL in the absence of metabolic activation and 2000.0 microg/mL in the presence of metabolic activation. In the second experiment, relevant toxic effects were observed at 500.0 microg/mL and above.
No relevant and reproducible increases in mutant frequency were observed at any concentration, neither in the absence or presence of metabolic activiation. Appropriate reference mutagens were used as positive controls, and showed a distinct increase in mutant frequencies.
In conclusion, it can be stated that during the described mutagenicity test, and under the experimental conditions reported, the test article did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, 6-hydroxy-2-naphthoic acid is considered to be non-mutagenic in this assay.
Reference
Pre-Test Cytotoxicity Experiment:
Concentration (microg/mL) | Duration of Treatment | S9 | Cloning Efficiency (%; absolute) | Cloning Efficiency (%; relative) |
Negative Control | 4 | - | 62.2 | 100.0 |
Solvent Control | 4 | - | 64.1 | 100.0 |
15.6 | 4 | - | 63.4 | 98.9 |
31.3 | 4 | - | 69.5 | 108.5 |
62.5 | 4 | - | 55.9 | 87.3 |
125.0 | 4 | - | 56.6 | 88.4 |
250.0 | 4 | - | 60.9 | 95.1 |
500.0 | 4 | - | 60.9 | 95.1 |
1000.0 | 4 | - | 23.2 | 36.2 |
2000.0 | 4 | - | 0.0 | 0.0 |
Negative Control | 4 | + | 56.2 | 100.0 |
Solvent Control | 4 | + | 58.7 | 100.0 |
15.6 | 4 | + | 53.8 | 91.6 |
31.3 | 4 | + | 55.6 | 94.8 |
62.5 | 4 | + | 56.3 | 96.0 |
125.0 | 4 | + | 58.5 | 99.7 |
250.0 | 4 | + | 54.5 | 92.7 |
500.0 | 4 | + | 57.4 | 97.8 |
1000.0 | 4 | + | 49.5 | 84.3 |
2000.0 | 4 | - | 0.0 | 0.0 |
Negative Control | 24 | - | 76.4 | 100.0 |
Solvent Control | 24 | - | 70.7 | 100.0 |
15.6 | 24 | - | 78.0 | 110.4 |
31.3 | 24 | - | 81.7 | 115.5 |
62.5 | 24 | - | 77.2 | 109.2 |
125.0 | 24 | - | 59.4 | 84.0 |
250.0 | 24 | - | 56.6 | 80.1 |
500.0 | 24 | - | 45.0 | 63.7 |
1000.0 | 24 | - | 4.1 | 5.7 |
2000.0 | 24 | - | 0.0 | 0.0 |
Main Experiment: Experiment 1, Culture 1
Concentration | S9 | Cloning Efficiency (relative % survival) | Cloning Efficiency Factor | Mutant Colonies per 10^6 cells |
Negative Control (untreated cells) | - | 100.0 | 0.68 | 12.8 |
Solvent Control | - | 100.0 | 0.68 | 9.6 |
Positive Control with EMS (300.0 microg/mL) | - | 92.0 | 0.63 | 262.8 |
62.5 microg/mL | - | 103.7 | *culture not continued | *culture not continued |
125.0 microg/mL | - | 94.0 | 0.69 | 13.8 |
250.0 microg/mL | - | 107.5 | 0.74 | 2.2 |
500.0 microg/mL | - | 105.0 | 0.69 | 7.1 |
1000.0 microg/mL | - | 85.2 | 0.69 | 2.6 |
1500.0 microg/mL | - | 0.0 | 0.68 | 2.7 |
Negative Control (untreated cells) | 100.0 | 0.82 | 2.9 | |
Solvent Control | + | 100.0 | 0.74 | 6.1 |
Positive Control (DMBA 2.5 microg/mL) | + | 53.0 | 0.74 | 721.0 |
125.0 microg/mL | + | 106.7 | 0.91 | 2.1 |
250.0 microg/mL | + | 105.1 | 0.76 | 7.6 |
500.0 microg/mL | + | 82.2 | 0.91 | 7.3 |
1000.0 microg/mL | + | 90.9 | 0.74 | 7.4 |
1500.0 microg/mL | + | 93.3 | 0.46 | 8.8 |
2000.0 microg/mL | + | 13.4 | 0.41 | 4.4 |
Main Experiment: Experiment 1, Culture 2
Concentration | S9 | Cloning Efficiency (relative % survival) | Cloning Efficiency Factor | Mutant Colonies per 10^6 cells |
Negative Control (untreated cells) | - | 100.0 | 0.50 | 7.8 |
Solvent Control | - | 100.0 | 0.44 | 5.5 |
Positive Control with EMS (300.0 microg/mL) | - | 105.0 | 0.67 | 267.0 |
62.5 microg/mL | - | 103.8 | *Culture not continued | *Culture not continued |
125.0 microg/mL | - | 108.8 | 0.62 | 5.7 |
250.0 microg/mL | - | 97.2 | 0.40 | 9.2 |
500.0 microg/mL | - | 96.2 | 0.52 | 8.2 |
1000.0 microg/mL | - | 88.9 | 0.33 | 14.9 |
1500.0 microg/mL | - | 0.0 | 0.45 | 4.9 |
Negative Control (untreated cells) | + | 100.0 | 0.54 | 6.5 |
Solvent Control | + | 100.0 | 0.54 | 2.7 |
Positive Control (DMBA 2.5 microg/mL) | + | 45.4 | 0.33 | 1417.4 |
125.0 microg/mL | + | 145.1 | 0.44 | 12.8 |
250.0 microg/mL | + | 93.1 | 0.41 | 4.5 |
500.0 microg/mL | + | 95.7 | 0.50 | 5.7 |
1000.0 microg/mL | + | 90.6 | 0.44 | 22.7 |
1500.0 microg/mL | + | 92.9 | 0.42 | 6.9 |
2000.0 microg/mL | + | 1.1 | 0.45 | 3.6 |
Main Experiment: Experiment 2, Culture 1
Concentration | S9 | Cloning Efficiency (relative % survival) | Cloning Efficiency Factor | Mutant Colonies per 10^6 cells |
Negative Control | - | 100.0 | 0.69 | 5.8 |
Solvent Control | - | 100.0 | 0.85 | 9.8 |
Positive Control with EMS (300.0 microg/mL) | - | 76.9 | 0.49 | 1064.7 |
62.5 microg/mL | - | 100.0 | *Culture not continued | *Culture not continued |
125.0 microg/mL | - | 88.6 | 0.76 | 4.9 |
250.0 microg/mL | - | 81.3 | 0.71 | 3.0 |
500.0 microg/mL | - | 59.7 | 0.67 | 10.6 |
750.0 microg/mL | - | 27.0 | 0.63 | 11.2 |
1000.0 microg/mL | 25.4 | 0.63 | 4.6 |
Main Experiment: Experiment 2, Culture 2
Concentration | S9 | Cloning Efficiency (relative % survival) | Cloning Efficiency Factor | Mutant Colonies per 10^6 cells |
Negative Control | - | 100.0 | 0.86 | 6.6 |
Solvent Control | - | 100.0 | 0.92 | 5.0 |
Positive Control with EMS (300.0 microg/mL) | - | 75.6 | 0.62 | 707.5 |
62.5 microg/mL | - | 100.4 | *Culture not continued | *Culture not continued |
125.0 microg/mL | - | 85.6 | 0.81 | 14.1 |
250.0 microg/mL | - | 78.3 | 0.67 | 3.3 |
500.0 microg/mL | - | 51.9 | 0.63 | 5.1 |
750.0 microg/mL | - | 28.3 | 0.76 | 8.0 |
1000.0 microg/mL | 21.5 | 0.73 | 9.7 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In all genotoxicity studies performed, there were no positive findings. This included the following:
- In vitro:
Bacterial Mutagenicity - (6 -HNA and 3 -HNA)
Mutation in Mammalian Cells (6 -HNA)
Chromosomal aberration in Mammalian Cells (6 -HNA)
- In vivo:
Chromosomal aberration in mice (6 -HNA and 3 -HNA)
Justification for selection of genetic toxicity endpoint
Taken together, the total evidence for genetic toxicity derived from the substance of record, 6-hydroxy-2-naphthoic acid (6-HNA) and the read-across substance support the finding that 6-HNA is not genotoxic. This is based on the lack of positive findings in any genotoxicity study.
Justification for classification or non-classification
Based on the lack of positive response in any of the genotoxicity assays, for either 6 -HNA or 3 -HNA, neither substance meet the criteria for classification as genotoxic.
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