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EC number: 436-710-6 | CAS number: 756-13-8
- 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
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- 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
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
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- Endpoint summary
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- 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
Gene mutation (Bacterial Reverse Mutation Assay/Ames test): The substance 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone did not induce mutagenicity in S. typhimurium TA1535, TA1537, TA100, TA98 and Escherichia coli WP2 uvrA in the presence or absence of Aroclor 1254-induced rat liver S9 metabolic activation (OECD 471, GLP);
Gene mutation (mammalian cell gene mutation assay): there was no evidence of induced mutant colonies over background in Chinese hamster lung fibroblast (V79) cells exposed to 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone in the presence or absence of mammalian metabolic activation (phenobarbital and ß-naphthoflavone-induced rat liver S9) (OECD 476/GLP).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: other guideline: EC Directive 2000/32, B13/14 OECD 471, 1997
- GLP compliance:
- yes
- Type of assay:
- other: not available
- Species / strain / cell type:
- bacteria, other: Salmonella typhimurium (TA1535, TA1537, TA100 and TA98) Escherichia coli WP2uvrA
- Metabolic activation system:
- S9 liver homogenate of rat induced with Aroclor 1254.
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 10 ... 5000 μg/plate
Concentration range in the main test (without metabolic activation): 10 ... 5000 μg/plate - Vehicle / solvent:
- Solvent: ethanol
- Species / strain:
- other: as specified above
- Metabolic activation:
- with
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 5000 μg/plate)
- Species / strain:
- other: as specified above
- Metabolic activation:
- without
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 5000 μg/plate)
- Species / strain:
- other: as specified above
- Metabolic activation:
- with
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 5000 μg/plate)
- Species / strain:
- other: as specified above
- Metabolic activation:
- without
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- (> 5000 μg/plate)
- Additional information on results:
- Observations:
The bacterial background lawn was not reduced at all concentrations tested and no biologically relevant decrease in the number of revertants was observed. The presence of 5 and 10% (v/v) liver microsomal activation did not influence these findings. T-7479 did not induce a dose-related, two-fold increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in an independently repeated experiment. - Remarks on result:
- other: Test system: preliminary test
- Conclusions:
- Interpretation of results
negative with metabolic activation
negative without metabolic activation - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- an in vitro cytogenicity study in mammalian cells or in vitro micronucleus study does not need to be conducted because adequate data from an in vivo cytogenicity test are available
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 8th May 2018 - 24th August 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian cell gene mutation test using the Hprt and xprt genes
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Shanghai Waysmos Fine Chemical Co., LTD.; 8180402
- Purity: 99.83%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: store in cool, protected from light
- Stability under test conditions: instable after repeated contact to air and to light
- Target gene:
- HPRT
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: ATCC, CCL-93
- Suitability of cells: V79 cells in vitro have been widely used to examine the ability of chemicals to induce cytogenetic changes and thus identify potential carcinogens or mutagens.
- Cell cycle length, doubling time or proliferation index: 12 - 14 h doubling time
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: Minimal Essential Medium (MEM) and cultured at a humidified atmosphere of 5% CO2 and at 37 °C incubation temperature.
- Properly maintained: Yes
- Periodically checked for Mycoplasma contamination: Yes
- Periodically 'cleansed' against high spontaneous background: Yes; For purifying the cell population of pre-existing HPRT- mutants cells were exposed to HAT medium containing 10 µM hypoxanthine, 3.2 µM aminopterin, 5 µM thymidine and 10 µM glycine for several cell doublings (2 - 3 days) with a subsequent recovery period in medium supplemented with 10 µM hypoxanthine and 5 µM thymidine - Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital and Beta-naphthoflavone-induced rat liver S9
- Test concentrations with justification for top dose:
- Preliminary test: 25, 50, 100, 250, 500, 1000, 1500 and 2000 µg/mL
Main tests (4 hrs; + and – S9): 25, 50, 100, 250, 500, 1000, 1500 and 2000 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: A solubility test was performed with different solvents and vehicles. Based on the results of the solubility test ethanol was be used as solvent.
The test item was dissolved in ethanol and different stock solutions were prepared. The stock solutions were diluted with cell culture medium and added to the cells. The solvent was compatible with the survival of the cells and the S9 activity. - Untreated negative controls:
- yes
- Remarks:
- Medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium;
DURATION
- Exposure duration: 4 hrs + and – S9
- Expression time (cells in growth medium): 7-9 days
- Selection time (if incubation with a selection agent): 9-11 days (mutant frequency); 6-8 days (cloning efficiency)
SELECTION AGENT (mutation assays): selective medium containing 11 µg/mL 6-thioguanine
NUMBER OF REPLICATIONS: Single cell culture (test item; positive controls); duplicates (solvent and medium negative controls)
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: After the selection period, colonies were fixed with methanol, stained with Giemsa and counted.
NUMBER OF CELLS EVALUATED: 4 x 10~5 cells (mutant selection); 200 cells in 2 flasks (cloning efficiency)
DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity was evaluated by relative survival (RS). The cloning efficiency (CE) of cells plated immediately after treatment was adjusted by any loss of cells during treatment as compared with adjusted cloning efficiency in negative / solvent controls (assigned a survival of 100%). - Evaluation criteria:
- A test chemical is considered to be clearly negative if, in all experimental conditions examined
- none of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
- there is no concentration-related increase when evaluated with an appropriate trend-test
- all results are inside the distribution of the historical negative control data
A test chemical is considered to be clearly positive if, in any of the experimental conditions examined
- at least one of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control, and
- the increase is concentration-related when evaluated with an appropriate trend test, and
- any of the results are outside the distribution of the historical negative control data.
- if there is by chance a low spontaneous mutant frequency in the corresponding negative and solvent controls a concentration related increase of the mutations within their range has to be discussed.
According to the OECD guideline, the biological relevance is considered first for the interpretation of results. - Statistics:
- The non-parametric Mann-Whitney test was applied to the mutation data to prove the dose groups for any significant difference in mutant frequency compared to the negative/solvent controls. Mutant frequencies of the negative/solvent controls were used as reference.
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Remarks:
- 4 hrs
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: The pH-value detected with the test item was within the physiological range (pH 7.0 ± 0.4).
- Effects of osmolality: Osmolality of the highest test item concentration was 472 mOsm/kg.
- Precipitation: No precipitation of the test item was noted in the experiments.
RANGE-FINDING/SCREENING STUDIES:
The toxicity of the test item was determined in a pre-experiment. Eight concentrations [25, 50, 100, 250, 500, 1000, 1500 and 2000 µg/mL] were tested with and without metabolic activation for the 4 h exposure assay (Table 1, 2). Toxicity of the test item was evaluated using the relative survival (RS). A cytotoxic effect is observed as soon as the relative survival decreased below 70%. The test item was tested at the following concentrations in the main experiments: without and with metabolic activation - 25, 50, 100, 250, 500, 1000, 1500 and 2000 µg/mL
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: Yes; January 2015 – April 2018
- Negative (solvent/vehicle) historical control data: Yes; January 2015 – April 2018 - Conclusions:
- In an in vitro mammalian cell gene mutation test, the test item 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese Hamster.
- Executive summary:
In an in vitro gene mutation study in mammalian cells (HPRT; 183288), Chinese hamster lung fibroblasts (V79) were exposed to 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone (99.83%) in ethanol at concentrations of 25, 50, 100, 250, 500, 1000, 1500 and 2000 µg/mL for 4 hrs with and without phenobarbital and ß-naphthoflavone-induced rat liver S9 metabolic activation.
1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone was tested up to the limits of cytotoxicity. The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background in the presence or absence of metabolic activiation.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Mammalian erythrocyte micronucleus test: 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanon did not increase the mean frequency of micronucleated polychromatic erythrocytes in the bone marrow of male NMLI treated mice compared to controls. 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone is not clastogenic in the micronucleus test.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- other: Data sharing dispute
- Adequacy of study:
- key study
- Study period:
- October 2005 to February 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other:
- Remarks:
- other: Study performed by OECD guidelines and under GLP with no deviations. All finding clearly sup port the "not clastogenic" conclusions
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test) in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles river, Sulzfeld, Germany
- Age at study initiation: 6 weeks old
- Housing: polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.7-22.1 deg C.
- Humidity (%): 30 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To: October to Dec 2005 - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: 1% CMC
- Justification for choice of solvent/vehicle: Suitably stable emulsion
- Concentration of test material in vehicle:200 mg/mL
- Amount of vehicle (if gavage or dermal): 10mL/kg - Duration of treatment / exposure:
- Single exposure
- Frequency of treatment:
- Once
- Post exposure period:
- 24, 48 hours
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide;
- Justification for choice of positive control(s): Common usage
- Doses / concentrations: 50 mg/kg - Tissues and cell types examined:
- Bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: According to OECD Guidelines
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Single injections with collection after 24 and 48 hours.
DETAILS OF SLIDE PREPARATION: Slides were automatically stained using the "Wright-stain-procedure"
METHOD OF ANALYSIS: The number of micronucleated polychromatic erythrocytes was counted in 2000 polychromatic erythrocytes. Averages and standard deviations were calculated - Evaluation criteria:
- All validation critieria were met.
a. Positive control substance performed as desired.
b. Incidence of micronucleated polychromatic erhthrocytes were within historical control ranges. Me an +/- 3 standard deviations - Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 2000 mg/kg
- Solubility: suspension
- Clinical signs of toxicity in test animals: negative
- Evidence of cytotoxicity in tissue analyzed:none
- Rationale for exposure: well tolerated high dose
- Harvest times: Study duration of 3 days
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): None
- Ratio of PCE/NCE (for Micronucleus assay): None
- Appropriateness of dose levels and route: Appropriate
- Statistical evaluation: Yes - Conclusions:
- Negative - not clastogenic under the conditions of this assay.
- Executive summary:
MTDID 5789 (Lot #2) was tested in the Micronucleus Test in mice, to evaluate its genotoxic effect on erythrocytes in bone marrow. The study procedures described in this report were based on the most recent OECD and EEC guidelines. Batch Lot #2 of MTDID 5789 was a clear colourless liquid with a purity of 99.91%. The test substance was emulsified in 1% (w/v) carboxymethylcellulose. Five male animals were used in each of the four treatment groups, including negative and positive controls. All groups received a single intraperitoneal injection. The negative and positive control groups were treated with vehicle and 50 mg/kg body weight of cyclophosphamide (CP), respectively. Animals were dosed with MTDID 5789 at 2000 (two groups) mg/kg body weight. All animals showed no abnormalities after dosing. Bone marrow of the groups treated with MTDID 5789 was sampled 24 or 48 hours after dosing. Bone marrow of the negative and positive control groups was harvested 24 and 48 hours after dosing, respectively.
No increase in the mean frequency of micronucleated polychromatic erythrocytes was observed in the polychromatic erythrocytes of the bone marrow of animals treated with MTDID 5789. The incidence of micronucleated polychromatic erythrocytes in the bone marrow of all negative control animals was within the historical solvent control data range. Cyclophosphamide, the positive control substance, induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes. Hence, both criteria for an acceptable assay were met. The groups that were treated with MTDID 5789 showed no decrease in the ratio of polychromatic to normochromatic erythrocytes compared to the vehicle controls, which reflects a lack of toxic effects of this compound on the erythropoiesis. The groups that were treated with cyclophosphamide showed an expected decrease in the ratio of polychromatic to normochromatic erythrocytes compared to the vehicle controls, demonstrating toxic effects on erythropoiesis.
It is concluded that MTDID 5789 is not clastogenic in the micronucleus test under the experimental conditions described in this report.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
There is one in vitro reverse gene mutation assay in bacteria and one in vitro gene mutation study in mammalian cells available for
1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone. The in vitro cytogenicity study is waived as an in vivo mammalian erythrocyte micronucleus test in mice is available.
In vitro
In a reverse gene mutation assay in bacteria (OECD 471/GLP), strains of S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvr A were exposed to 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone in ethanol at concentrations of 10 -5000 µg/plate in the presence and absence of Aroclor 1254-induced rat liver S9 metabolic activation. 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone was tested up to the limit concentration (5000 µg/plate). The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.
In an in vitro gene mutation study in mammalian cells (HPRT; OECD 476/GLP), Chinese hamster lung fibroblasts (V79) were exposed to 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone (99.83%) in ethanol at concentrations of 25, 50, 100, 250, 500, 1000, 1500 and 2000 µg/mL for 4 hrs with and without phenobarbital and ß-naphthoflavone-induced rat liver S9 metabolic activation. 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone was tested up to the limits of cytotoxicity. The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background in the presence or absence of metabolic activiation.
In vivo
In a mammalian erythrocyte micronucleus test (OECD 474/GLP), groups of male NMRI mice (5/dose) were treated intraperitoneally with 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone (99.91%) in 1% (w/v) carboxymethylcellulose at a single dose of 2000 mg/kg bw. Bone marrow cells were harvested at 24h and 48 hrs post-treatment. 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone was tested at an adequate dose. The positive control (cyclophosphamide) induced the appropriate response. No increase in the mean frequency of micronucleated polychromatic erythrocytes was observed in the bone marrow of treated animals compared to controls. 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl )-3-pentanone is not clastogenic in the micronucleus test.
The results from these studies are suitable for use in the human health risk assessment.
Justification for classification or non-classification
Based on the available information in the dossier, the substance 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-pentanone does not need to be classified for germ cell mutagenicity when the criteria outlined in Annex I of 1272/2008/EC are applied.
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