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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
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- Density
- Particle size distribution (Granulometry)
- Vapour pressure
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
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- 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
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- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Genetic toxicity: in vitro
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 28 - September 12, 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 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: mammalian cell gene mutation assay in mouse lymphoma L5178Y cells
Test material
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature protected from light
- Solubility and stability of the test substance in the solvent/vehicle: 5 mg/mL in 0.25% THF
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: A stock solution of the test item was made with 0.25% THF. This stock solution was then diluted in RPMI and 5% HS.
- Final preparation of a solid: The test solution was then soniticated for 10 minutes at 37 degree C.
FORM AS APPLIED IN THE TEST (if different from that of starting material): Solution
Method
- Target gene:
- TK locus
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Eurofins Munich cell bank
- Cell cycle length, doubling time or proliferation index: 10-12 hr doubling time
- Whether whole blood or separated lymphocytes were used if applicable: lymphoma cells
- Methods for maintenance in cell culture if applicable: Thawed stock cultures are maintained in RPMI 1640 complete medium.
- Modal number of chromosomes: 40
MEDIA USED
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 10, 20, 50, 100, 200, and 300 µg/mL
Top dose based on results of toxicity pre-experiment which found precipitation at concentrations of 400 µg/mL and above. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: THF
- Justification for choice of solvent/vehicle: THF was chosen due to the solubility of the test item in that solvent as compared to other solvents.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- ethylmethanesulphonate
- methylmethanesulfonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in suspension of 11 mL RPMI medium and 5% horse serum
- Cell density at seeding (if applicable): 1 x 10E07
DURATION
- Preincubation period: 1-3 days
- Exposure duration: 4 hrs
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 12 days
- Fixation time (start of exposure up to fixation or harvest of cells): 14 days (8 days for cloning efficiency experiment)
SELECTION AGENT (mutation assays): RPMI with 20% horse serum, 100 U/100 µg/mL penicillin/streptomycin, 1 mM sodium pyruvate, 2 mM L-glutamine, 25 mM HEPES, 2.5 µg/mL amphotericin B, 5 µg/mL TFT
NUMBER OF REPLICATIONS: 4
NUMBER OF CELLS EVALUATED: all
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency - Evaluation criteria:
- The test substance is considered mutagenic if the following criteria were met:
induced mutant frequency of >= 126 mutants per 10E06 cells
dose-dependent increase in mutant frequency
increased occurrence of small colonies >= 40% of all colonies - Statistics:
- Mean mutant frequency
Mean induced mutant frequency
p-value
Results and discussion
Test results
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: yes, at hightest dose level of 300 µg/mL
RANGE-FINDING/SCREENING STUDIES: A range-finding study was performed at concentrations of 10, 30, 100, 200, 400, and 1000 µg/mL with and without metabolic activation. Precipitation was seen at the 400 and 1000 µg/mL concentrations both with and without metabolic activation.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data:
Ethylmethanesulfonate (300 µg/mL): range - 318.7-2919.0, mean - 726.5, standard deviation - 203.5
Methylmethanesulfonate (10 µg/mL): range - 376.4-2416.1, mean - 763.4, standard deviation - 421.6
Benzo[a]pyrene (2.5 µg/mL): range - 303.6-1267.2, mean - 635.9, standard deviation - 167.8
- Negative (solvent/vehicle) historical control data:
Negative without S9: range - 50.1-170.3, mean - 87.9, standard deviation - 25.5
Negative with S9: range - 50.1-165.9, mean 85.1, standard deviation - 24.3
Any other information on results incl. tables
Mouse Lymphoma Assay Results – Without Metabolic Activation
Concentration |
Relative Cloning Efficiency (%) |
Relative Total Growth (%) |
Mutant Frequency (mutants/10E06 cells) |
Induced Mutant Frequency (mutants/10E06 cells) |
Control 1 |
102.9 |
106.4 |
69.5 |
-- |
Control 2 |
98.0 |
100.3 |
69.5 |
-- |
Solvent Control |
100.0 |
100.0 |
64.9 |
-- |
10 µg/mL |
106.5 |
109.8 |
71.8 |
6.9 |
25 µg/mL |
85.1 |
86.7 |
64.6 |
-0.3 |
50 µg/mL |
102.9 |
97.3 |
86.5 |
21.6 |
100 µg/mL |
87.7 |
81.2 |
73.9 |
9.0 |
200 µg/mL |
104.7 |
86.6 |
69.0 |
4.2 |
300 µg/mL (Precipitate observed) |
93.4 |
84.1 |
61.6 |
-3.3 |
Ethylmethanesulfonate* |
91.9 |
73.0 |
649.0 |
584.2 |
Methylmethanesulfonate* |
62.8 |
46.6 |
631.5 |
566.7 |
* Global Evaluation Factor exceeded and statistically significant increase in mutant frequency seen
Mouse Lymphoma Assay Results – With Metabolic Activation
Concentration |
Relative Cloning Efficiency (%) |
Relative Total Growth (%) |
Mutant Frequency (mutants/10^6 cells) |
Induced Mutant Frequency (mutants/10^6 cells) |
Control 1 |
94.4 |
89.4 |
63.7 |
-- |
Control 2 |
107.0 |
105.6 |
63.7 |
-- |
Solvent Control |
100.0 |
100.0 |
80.2 |
-- |
10 µg/mL |
89.0 |
96.6 |
91.8 |
11.6 |
25 µg/mL |
112.3 |
119.5 |
71.2 |
-8.9 |
50 µg/mL |
91.6 |
84.8 |
68.4 |
-11.8 |
100 µg/mL |
100.4 |
95.5 |
49.6 |
-30.6 |
200 µg/mL |
98.9 |
96.2 |
72.7 |
-7.4 |
300 µg/mL (Precipitate observed) |
114.2 |
102.7 |
60.4 |
-19.8 |
Benzo[a]pyrene* |
90.3 |
64.4 |
702.5 |
622.4 |
* Global Evaluation Factor exceeded and statistically significant increase in mutant frequency seen
Applicant's summary and conclusion
- Conclusions:
- The test substance is non-mutagenic.
- Executive summary:
The mutagenicity of the test substance was determined in an OECD Guideline 490 study. The mutagenicity of the test substance was determined at concentrations of 10, 20, 50, 100, 200, and 300 µg/mL both with and without metabolic activation. THF was used as a solvent. Negative, solvent, and positive controls were used. Precipitation was seen at the highest test concentration of 300 µg/mL. The test substance was not cytotoxic, nor was it mutagenic.
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.
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