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EC number: 428-100-3 | CAS number: 94239-04-0
- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Harmonised Tripartite Guideline S2A and S2B
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- -
- EC Number:
- 428-100-3
- EC Name:
- -
- Cas Number:
- 94239-04-0
- Molecular formula:
- C6H3NF4
- IUPAC Name:
- 2-fluoro-6-(trifluoromethyl)pyridine
- Details on test material:
- - Purity: 99.54%
Constituent 1
- Specific details on test material used for the study:
- Substance ID: F6TF
Lot #: P2
Purity: 99.54%
Test animals
- Species:
- rat
- Strain:
- other: Alpk:APfSD
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 287 - 383 g
- Housing: housed on mobile rat cage racks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light followed by 12 hours darkness
Administration / exposure
- Route of administration:
- inhalation: vapour
- Vehicle:
- dried filtered air
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: nose only
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2 tiered nose-only exposure chamber
- Source and rate of air: dry filtered air
- System of generating vapour: atmospheres were generated by metering appropriate amounts of liquid test substance on to the top of a water bath heated condenser column (45°C) using a Hamilton Microlab pump. A counterflow of clean dry compressed air (25 L/min) was used to pass the resultant vapour to a 2 tiered nose-only exposure chamber
TEST ATMOSPHERE
- Brief description of analytical method used: Test atmospheres were sampled by trapping the test substance on Carbotrap C 20/40 mesh in a desorption tube, followed by thermal desorption and quantification using gas chromatography.
- Samples taken from breathing zone: yes - Duration of treatment / exposure:
- 4 hours
- Frequency of treatment:
- single
Doses / concentrationsopen allclose all
- Dose / conc.:
- 200 ppm
- Dose / conc.:
- 400 ppm
- Dose / conc.:
- 800 ppm
- No. of animals per sex per dose:
- 200 and 400 ppm - 5/dose
800 ppm - 10/dose - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - positive control: cyclophosphamide
- Route of administration: The positive control substance was prepared as a solution in double deionised water and was dosed at a volume of l0 mL/kg bodyweight. A group of rats was given a single oral dose of the positive control substance to coincide with the end of the inhalation exposure period.
- Doses / concentrations: l0 mL/kg bodyweight
Examinations
- Tissues and cell types examined:
- immature erythrocytes from rat bone marrow taken from the femur
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: The highest concentration represents the maximum tolerated dose (MTD) based on patterns of clinical signs and lethalities observed in a previous rat toxicity study.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Groups of male rats were exposed by the inhalation route for a single 4 hour period to either dried filtered air or the test substance at nominal concentrations of 200, 400 and 800 ppm. Bone marrow samples were taken approximately 24 hours after the end of the exposure period for the vehicle control and the test substance at dose levels of 800, 400 and 200 ppm and 48 hours after the end of the exposure period for the vehicle control and the test substance at 800ppm. Bone marrow samples were taken 24 after dosing for the positive control.
DETAILS OF SLIDE PREPARATION: Femurs were removed and stripped clean of muscle. The iliac end of the femur was removed and a fine paint brush was rinsed in saline, wiped to remove the excess and wetted with a solution of albumin (6% w/v in physiological saline). This was then dipped into the marrow canal and two smears were painted on an appropriately labelled clean, dry microscope slide. This procedure was repeated to give four smears of marrow per slide. The slides were allowed to air dry and were stained with acridine orange.
METHOD OF ANALYSIS: Slides were coded and scored blind. Two thousand immature erythrocytes were examined for the presence of micronuclei for each animal. The slides were also examined for evidence of cytotoxicity, which may be manifest by alterations in the ratio of different cell types in the bone marrow. This was assessed by counting the ratio of immature to mature erythrocytes in a sample of 1000 erythrocytes. - Evaluation criteria:
- The data have been interpreted as follows:
a) No statistically significant increase in the incidence of micronucleated immature erythrocytes above concurrent vehicle control incidences -NEGATIVE.
b) A statistically significant increase in the incidence of micronucleated immature erythrocytes above the concurrent vehicle control incidences but which falls within the laboratory historical vehicle control range - NEGATIVE.
c) A statistically and biological significant increase in the incidence of micronucleated immature erythrocytes which is in excess of a three-fold increase when compared with both historical and concurrent vehicle control incidences - POSITIVE.
d) An incidence of micronucleated immature erythrocytes which is statistically significantly different from the concurrent vehicle control incidences, but less than 3-fold in excess of both historical and concurrent vehicle control incidences may require further evaluation. - Statistics:
- The data for the incidence of micronucleated immature erythrocytes were transformed using a square root transformation, prior to analysis. The data for the percentages of immature erythrocytes were transformed using the double arcsine transformation of Freeman and Tukey, prior to analysis.
Analyses were carried out using the MIXED procedure in SAS. Each treatment group mean was compared with the control group mean at the corresponding sampling time using a one-sided Student's t-test, based on the error mean square in the analysis.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
Any other information on results incl. tables
Clinical signs: stains around nose, decreased activity, tiptoe gait, abnormal breathing, reduced stability and reduced response to sound
Mortality: one male found dead before sampling time, macroscopic abnormalities included mesenteric/renal lymph nodes, mottled/pale areas on liver, pelvic dilatation of the kidney, distended bladder, gas-filled caecum and a diaphragmatic hernia on the liver
Genotoxicity: No statistically or biologically significant increases in the incidence of micronucleated immature erythrocytes were observed. No statistically significant differences in the percentage of immature erythrocytes between vehicle control and test substance were observed
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the test, the test substance is neither clastogenic nor aneugenic in the rat bone marrow micronucleus test.
- Executive summary:
An inhalation micronucleus study was conducted in rats to determine whether the test material induces an increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow. In this study, groups of male rats were placed in exposure chambers and exposed single nose-only to target concentrations of 200, 400, and 800 ppm for 4 hours. Bone marrow smears were prepared approximately 24 and 48 hours after exposure and 2000 immature erythrocytes per animal were evaluated for the presence of micronuclei.
No statistically or biologically significant increases in the incidence of micronucleated immature erythrocytes were observed. No statistically significant differences in the percentage of immature erythrocytes between vehicle control and test substance were observed. Under the conditions of the test, the test substance is neither clastogenic nor aneugenic in the rat bone marrow micronucleus test.
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