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EC number: 944-041-0 | CAS number: -
- 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:
- other: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1992
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Source study has reliability 1. Details on the read across are attached in section 13.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Cytotest Cell Research GmbH & Co. KG
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Similar Substance 01
- IUPAC Name:
- Similar Substance 01
- Test material form:
- solid: particulate/powder
Constituent 1
Method
- Target gene:
- HGPRT (hypoxanthine-guanine phosphoribosyl transferase)
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: HAM's F12 (Seromed, D-1000 Berlin, FRG) supplemented with 10 % fetal calf serum (FCS; Seromed)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat liver S9 microsomal fraction
- Test concentrations with justification for top dose:
- Experiment 1
30, 100, 200, 300, 400, 800 µg/ml (without S9 mix)
1, 5, 20, 100, 1000, 2000, 2700, 3420 µg/ml (with S9 mix)
Experiment 2
80, 300, 600, 800, 1000, 1200 µg/ml (without S9 mix)
342, 1000, 1692, 2000, 2700, 3420 µg/ml (with S9 mix)
Experiment 3
1, 5, 10, 20, 30, 50 µg/ml (with S9 mix) - Vehicle / solvent:
- - Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle: substance is not soluble in water.
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 h
- Expression time (cells in growth medium): 7 or 16 days; colony staining with 10 % methylene blue in 0.01 % KOH solution.
NUMBER OF REPLICATIONS: in duplicate per experimental point
NUMBER OF CELLS EVALUATED: 10^6
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency. - Evaluation criteria:
- Test article is classified as positive if it induces either a significant concentration-related increase in the mutant frequency or a reproducible and significant positive response for at least one of the test points.
A test article producing neither a significant concentration-related increase in the mutant frequency nor a significant and reproducible positive response at any one of the test points is considered non-mutagenic in this system. - Statistics:
- Since the distribution of mutant cells does not follow known statistical models, an adequate statistical method is not available.
Results and discussion
Test results
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- reduced plating efficiency observed in some plates with and without metabolic activation
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- PRETEST
In a pre-test the colony forming ability of approximately 500 single cells (duplicate cultures per concentration level) after treatment with the test article was observed and compared to the controls. Toxicity of the test article was evidenced by a reduction in plating efficiency (PE). The plating efficiency of the CHO cells was reduced after treatment with 1000 µg/ml (without metabolic activation). With metabolic activation toxicity was observed after treatment with 2000 µg/ml and between 40 µg/ml and 300 µg/ml. Therefore, the first experiment was performed with six (without metabolic activation) and eight concentrations (with metabolic activation) ranging from 1 to 3420 µg/ml. - Remarks on result:
- other: all strains/cell types tested
Any other information on results incl. tables
Results:
Experiment | µg/ml | S9 mix | mean number cells/flask | factor | mean number mutant colonies/flask | mean number mutant colonies/10^6 cells | |
seeded | found | ||||||
1 | negative control | - | 542 | 280,5 | 0,52 | 2.8 ± 0.8 | 13,8 |
600, EMS | - | 530 | 186 | 0,35 | 61.0 ± 6.6 | 542,9 | |
30 | - | nc | |||||
100 | - | 618 | 298,5 | 0,48 | 1.4 ± 1.1 | 7 | |
200 | - | 608 | 362 | 0,6 | 2.4 ± 2.1 | 9,4 | |
300 | - | nc | |||||
400 | - | 612 | 459 | 0,75 | 5.2 ± 2.9 | 17,8 | |
800 | - | 610 | 423,5 | 0,69 | 3.8 ± 1.3 | 13,4 | |
negative control | + | 498 | 289,5 | 0,58 | 2.6 ± 1.1 | 12,1 | |
solvent control | + | 498 | 260,5 | 0,52 | 0.2 ± 0.4 | 0,8 | |
3850, DMBA | + | 519 | 123 | 0,24 | 109.4 ± 14.2 | 1215,6 | |
1 | + | nc | |||||
5 | + | nc | |||||
20 | + | nc | |||||
100 | + | 508 | 221 | 0,44 | 4.6 ± 2.9 | 28,6 | |
1000 | + | 525 | 233,5 | 0,44 | 1.2 ± 1.1 | 7,6 | |
2000 | + | nc | |||||
2700 | + | 454 | 273 | 0,6 | 0.8 ± 0.8 | 3,1 | |
3420 | + | 492 | 264 | 0,54 | 2.6 ± 1.7 | 13,5 | |
2 | negative control | - | 519 | 282,5 | 0,54 | 3.2 ± 2.9 | 13,8 |
600, EMS | - | 506 | 148,5 | 0,29 | 142.6 ± 3.5 | 1343,5 | |
80 | - | 529 | 253,5 | 0,48 | 1.4 ± 0.9 | 6,7 | |
300 | - | 504 | 232 | 0,46 | 1.4 ± 1.7 | 7,5 | |
600 | - | nc | |||||
800 | - | 522 | 294 | 0,56 | 0.2 ± 0.4 | 0,8 | |
1000 | - | 507 | 282 | 0,56 | 0.4 ± 0.5 | 1,7 | |
1200 | - | nc | |||||
negative control | + | 506 | 267 | 0,53 | 2.0 ± 0.7 | 8,4 | |
solvent control | + | 514 | 258 | 0,5 | 1.8 ± 1.1 | 8 | |
3850, DMBA | + | 500 | 159 | 0,32 | 153.0 ± 14.8 | 1048,5 | |
342 | + | 511 | 236,5 | 0,46 | 1.2 ± 1.3 | 5,8 | |
1000 | + | nc | |||||
1692 | + | 525 | 211 | 0,4 | 0.2 ± 0.4 | 1,3 | |
2000 | + | nc | |||||
2700 | + | 515 | 224,5 | 0,44 | 0.2 ± 0.4 | 1 | |
3420 | + | 503 | 251,5 | 0,5 | 2.0 ± 2.0 | 8,8 | |
3 | negative control | + | 530 | 341 | 0,64 | 1.2 ± 0.8 | 4,5 |
solvent control | + | 506 | 314 | 0,62 | 0.4 ± 0.5 | 1,7 | |
3850, DMBA | + | 504 | 298 | 0,59 | 77.2 ± 2.9 | 320,7 | |
1000 | + | 531 | 290,5 | 0,55 | 0.4 ± 0.5 | 2,1 | |
5000 | + | nc | |||||
10000 | + | 525 | 320 | 0,61 | 1.6 ± 1.5 | 6,2 | |
20000 | + | 504 | 260,5 | 0,52 | 0.2 ± 0.4 | 0,9 | |
30000 | + | 532 | 313 | 0,59 | 0.6 ± 0.5 | 2,4 | |
50000 | + | 519 | 264 | 0,51 | 0.4 ± 0.5 | 1,9 |
nc: culture not continued
Applicant's summary and conclusion
- Conclusions:
- No induction of gene mutation at the HGRPT locus in CHO cells.
- Executive summary:
Method
The potential of the test substance to induce gene mutations at the HGPRT locus using Chinese hamster ovary cells was tested in vitro with and without metabolic activation according to OECD guideline 476 (tested up to 3420 μg/ml).
Results
Cytotoxicity was observed in an intermediate concentration range around 20 µg/ml of test substance, presumably induced by inhibition of enzymes of the S9-mix. Test substance showed no mutagenic effects on the HGPRT locus of CHO cells.
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