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EC number: 284-868-8 | CAS number: 84988-79-4
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 05 Jan - 05 Mar 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study with acceptable restrictions (analytical purity of test substance not specified).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- yes
- Remarks:
- analytical purity of test substance not specified
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United Kingdom
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Reference substance 002
- Cas Number:
- 163961-32-8
- Details on test material:
- - Physical state: Amber liquid
- Analytical purity: no data
- Storage condition of test material: Room temperature in the dark
The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility of the Sponsor.
Constituent 1
Method
- Target gene:
- thymidine kinase
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - details on cell strain: L5178Y +/- 3.7.2c mouse lymphoma cells
- Type and identity of media: RPMI 1640 medium with Glutamax-l and HEPES buffer
- Properly maintained: yes
- Periodically "cleansed" against high spontaneous background: yes
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-Mix
- Test concentrations with justification for top dose:
- Experiment I: 4 hour treatment with and without S9 mix - 156.25, 312.5, 625, 1250, 2500, 5000 µg/mL
Experiment II: 24 hour treatment without and 4 hour treatment with S9 mix - 156.25, 312.5, 625, 1250, 2500, 5000 µg/mL
Experiment III: 4 hour treatment with S9 mix - 39.06, 78.13, 117.2, 156.25, 234.38, 312.5, 468.75, 625, 937.5, 1250 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Acetone
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ethylmethanesulphonate (EMS, 150 + 400 µg/mL without S9); Cyclophosphamide (CP, 2 µg/mL with S9 mix)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 h with and without metabolic activation increased to 24 h in the second experiment (without metabolic activation)
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 10-14 days
SELECTION AGENT (mutation assays): 5-fluorothymidine
NUMBER OF REPLICATIONS: 2
DETERMINATION OF CYTOTOXICITY
- Cell counts, viability after 2 days: the cell counts obtained immediately post treatment and over the 2-day expression period were used to calculate the % relative suspension growth that gives an indication of post treatment toxicity
OTHER:
The numbers of small and large colonies seen in the TFT mutation plates were also recorded - Evaluation criteria:
- - The vehicle control values have to be in range with historical data.
- Positive control chemicals should induce at least three to five fold increases in mutant frequency greater than the corresponding vehicle control.
- For a test material to demonstrate a mutagenic response it must produce a statistically significant increase in the induced mutant frequency (IMF) over the concurrent vehicle mutant frequency value. The IMF must exceed the Global Evaluation Factor (GEF).
- when a test material induces modest reproducible increases in the mutation frequencies that do not exceed the GEF value then scientific judgement will be applied. If the reproducible responses are significantly dose-related and include increases in the absolute numbers of mutant colonies then they may be considered to be toxicologically significant.
Results and discussion
Test results
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
A cloudy precipitate of the test material was observed at and above 78.13 µg/mL forming a greasy/oily precipitate at and above 1250 µg/mL.
RANGE-FINDING/SCREENING STUDIES:
In the 4-hour exposures, both in the absence and presence of metabolic activation (S9), there appeared to be variable exposure of the test material to the cells as indicated by the reductions in the Relative Suspension Growth (%RSG) at certain dose levels. This was considered to be due to the nature of the test material formulations. In the 24-hour exposure in the absence of S9 there was a greater reduction in %RSG values forming a plateau effect down the dose range. A cloudy precipitate of the test material was observed at and above 78.13 pglml forming a greasy/oily precipitate at and above 1250 pglml. Due to the variable levels of toxicity observed the maximum recommended dose of 5000 pgiml was investigated in Experiments I and II.
COMPARISON WITH HISTORICAL CONTROL DATA:
All results were within the ranges of historical control data.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
The dose range used in the preliminary toxicity test was 19.53 to 5000 µg/mL.
Due to the variable levels of toxicity observed the maximum recommended dose of 5000 µg/mL was investigated in experiments 1 and 2.
Any other information on results incl. tables
Table 1: Results for the Relative Suspension Growth (%RSG) in the preliminary toxicity test were as follows:
Dose (µg/mL) |
% RSG (-S9) 4-Hour Exposure |
% RSG (+S9) 4-Hour Exposure |
% RSG (-S9) 24-Hour Exposure |
0 |
100 |
100 |
100 |
19.53 |
88 |
84 |
61 |
39.06 |
83 |
92 |
61 |
78.13 |
74 |
92 |
56 |
156.25 |
91 |
78 |
58 |
312.5 |
85 |
78 |
53 |
625 |
75 |
64 |
55 |
1250 |
84 |
84 |
50 |
2500 |
85 |
77 |
44 |
5000 |
65 |
91 |
64 |
Table 2: Results from Experiment 1
Treatment (µg/mL) |
4-Hours without S9 |
Treatment (µg/mL) |
4-Hours with S9 |
||||
%RSG |
RTG |
MF§ |
%RSG |
RTG |
MF§ |
||
0 |
100 |
1.00 |
100.35 |
0 |
100 |
1.00 |
122.76 |
156.25 |
130 |
1.34 |
96.34 |
156.25 |
98 |
1.05 |
88.56 |
312.5 |
112 |
1.28 |
98.69 |
312.5 |
92 |
1.00 |
106.06 |
625 |
136 |
1.57 |
91.80 |
625 |
82 |
0.86 |
137.37 |
1250 |
129 |
1.20 |
138.71 |
1250 |
94 |
0.92 |
122.97 |
2500 |
127 |
1.47 |
82.69 |
2500 |
102 |
0.87 |
110.73 |
5000 |
152 |
1.43 |
119.09 |
5000 |
109 |
0.95 |
112.66 |
Linear Trend NS |
Linear Trend NS |
||||||
EMS 400 |
124 |
0.83 |
748.75 |
CP 2 |
94 |
0.51 |
951.61 |
Table 3: Results from Experiment 2
Treatment (µg/mL) |
24-Hours without S9 |
Treatment (µg/mL) |
4-Hours with S9 |
||||
%RSG |
RTG |
MF§ |
%RSG |
RTG |
MF§ |
||
0 |
100 |
1.00 |
88.69 |
0 |
100 |
1.00 |
131.27 |
156.25 |
63 |
0.69 |
95.98 |
156.25 |
47 |
0.41 |
210.65 |
312.5 |
66 |
0.62 |
57.47 |
312.5 |
58 |
0.46 |
229.00 |
625 |
72 |
0.77 |
99.53 |
625 |
35 |
0.33 |
213.23 |
1250 |
63 |
0.61 |
64.44 |
1250 |
88 |
0.82 |
150.73 |
2500 |
76 |
0.81 |
82.48 |
2500 |
113 |
1.03 |
128.99 |
5000 |
99 |
1.l2 |
90.36 |
5000 |
127 |
1.09 |
133.50 |
Linear Trend NS |
Linear Trend NS |
||||||
EMS 400 |
103 |
0.73 |
1021.46 |
CP 2 |
67 |
0.527 |
1305.55 |
Table 4: Results from Experiment 3
Treatment (µg/mL) |
4-Hours withS9 |
||
%RSG |
RTG |
MF§ |
|
0 |
100 |
1.00 |
165.58 |
39.06 |
110 |
0.98 |
151.66 |
78.13 |
101 |
1.03 |
185.56 |
117.2 |
61 |
0.41 |
167.55 |
156.25 |
50 |
0.39 |
170.51 |
234.38 |
138 |
1.32 |
174.72 |
312.5 |
124 |
1.32 |
128.11 |
468.75 |
64 |
0.63 |
176.42 |
625 |
60 |
0.41 |
228.91 |
937.5 |
63 |
0.46 |
190.85 |
1250 |
65 |
0.46 |
156.75 |
Linear Trend NS |
|||
CP 2 |
62 |
0.22 |
856.01 |
%RSG: Relative Suspension Growth
RTG : Relative Total Growth
MF§ : 5-TFT resistant mutants/10^6 viable cells 2 days after treatment
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative not mutagenic in mouse lymphoma cells
The test material did not induce any toxicologically significant increases in the mutant frequency at the TK +/- locus in L5l78Y cells and is therefore considered to be non-mutagenic under the conditions of the test.
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