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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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data provided are an assessment of the predicted toxicokinetic behavior of the test substance based on its physical-chemical properties and available toxicity data.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- This report is a toxicokinetic assessment based on information from the following toxicity studies:
- Acute oral toxicity in rats
- 4-hour Acute inhalation toxicity in rats
- 28-day Subacute inhalation in rats
- Skin sensitization in guinea pigs
- Skin irritation in rabbits
- Eye irritation in rabbits
- Bacterial mutation assay in S. typhimurium and E. coli
- Cytogenic assay in human lymphocytes
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: See cross-reference to other study
Constituent 1
- Specific details on test material used for the study:
- Substance ID: F6TF
Purity: 99.6% - Radiolabelling:
- no
Test animals
- Species:
- other: rat, guinea pig, rabbit, bacteria, human cells
- Sex:
- male/female
Administration / exposure
- Route of administration:
- other: See cross-reference to other study
- Vehicle:
- other: See cross-reference to other study
- Duration and frequency of treatment / exposure:
- See cross-reference to other study
Doses / concentrations
- Remarks:
- Doses / Concentrations:
See cross-reference to other study
- No. of animals per sex per dose / concentration:
- See cross-reference to other study
- Control animals:
- other: See cross-reference to other study
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- The toxicity of high dose levels of the test substance following both oral administration and inhalation exposure show that this substance is absorbed both across the gastrointestinal and pulmonary mucosa. There was no evidence of any dermal penetration of the test substance in the rabbit study, despite occlusion of the application sites, which would have promoted any absorption. Similarly, the negative dermal sensitization result in the guinea pig study provides no evidence of any absorption through skin in this species.
- Details on distribution in tissues:
- A clear dose response effect on liver weight was apparent during the repeated inhalation exposure study. This was accompanied by histopathological changes in the liver and perturbations in various clinical chemistry parameters.
Metabolite characterisation studies
- Metabolites identified:
- not measured
Any other information on results incl. tables
Based upon its structure, molecular weight and log P value, absorption of orally administered test substance across the gastrointestinal mucosa would be expected. Similarly, absorption through the lungs would be expected during inhalation exposure to the vapour. Its molecular weight is below the biliary exclusion limit in the rat, consequently, it would not be excreted directly in bile. The aqueous solubility of absorbed test substance would allow some direct urinary excretion. The absorbed molecule is therefore likely to be subject to biotransformation to promote excretion. The fluorine and trifluoromethyl moieties are unlikely to be subject to any metabolism. Ring hydroxylation is likely to be a predominate reaction and by analogy to trifluoromethylpyridine, would be expected to form metabolites of reduced toxicity. N-oxidation of the test substance is feasible, although sulphate conjugation of this product would be expected to protect against the potential toxicity of this metabolite.
Metabolism: In the bacterial mutation assays in S. typhimurium and E. coli, the test substance did not induce revertant colonies. Accordingly, it was concluded that the test substance was not mutagenic to S. typhimurium and E. coli treated in vitro in both the presence and absence of S-9 mix. Hence, no conclusions can be drawn about the metabolism of the test substance from this study. Using cultures of human lymphocytes, with an established low incidence of chromosomal aberrations in their peripheral blood lymphocytes, concentration-related reductions in mitotic activity were observed in cultures from these donors, thus demonstrating that the test substance is biologically active in this test system. In the presence of S-9 mix, the test substance caused a small but statistically significant increase (5.5%) in the percentage of aberrant cells, compared to the solvent control values in cultures from one of two experiments. In the absence on S-9 mix, statistically significant increases (up to 8%) were observed only in cultures treated for 20 hours. Accordingly, it was concluded that under the conditions of the assay, the test substance was weakly clastogenic to cultured human lymphocytes treated in vitro in both the presence and absence of S-9 mix. Hence, no conclusions can be drawn on the metabolism of the test substance from this study.
Applicant's summary and conclusion
- Conclusions:
- Toxicity studies show clear evidence for absorption of the test substance following oral and inhalation exposure. The aqueous solubility would allow some direct urinary excretion of the absorbed dose, but biotransformation would be expected.
Toxicity studies have shown clear evidence for the absorption of the test substance following both oral administration and inhalation exposure. There was no evidence of any dermal penetration of the test substance in the rabbit, despite occluded application; similarly, there was no evidence of any dermal absorption in the guinea pig sensitization study.
An assessment of the potential absorption of the test substance is also based upon its physico-chemical properties, which suggest that the intact molecule would be subject to absorption across the gastrointestinal mucosa following oral administration and also via the lungs during inhalation exposure. The aqueous solubility of the test substance would allow some direct urinary excretion of the absorbed dose, but biotransformation would be expected. The fluorine and trifluoromethyl moieties are unlikely to be subject to metabolism. Ring hydroxylation would be expected to be a predominate reaction and, by analogy to trifluoromethylpyridine, would form metabolites of less toxicity. N-oxidation is feasible, although sulphate conjugation of this product would be expected to protect against its potential toxicity. - Executive summary:
This report is a toxicokinetic assessment based on information from the following toxicity studies:
- Acute oral toxicity in rats
- 4-hour Acute inhalation toxicity in rats
- 28-day Subacute inhalation in rats
- Skin sensitization in guinea pigs
- Skin irritation in rabbits
- Eye irritation in rabbits
- Bacterial mutation assay in S. typhimurium and E. coli
- Cytogenic assay in human lymphocytes
Toxicity studies have shown clear evidence for the absorption of the test substance following both oral administration and inhalation exposure. There was no evidence of any dermal penetration of the test substance in the rabbit, despite occluded application. Similarly, there was no evidence of any dermal absorption in the guinea pig sensitization study. An assessment of the potential absorption of the test substance is also based upon its physico-chemical properties, which suggest that the intact molecule would be subject to absorption across the gastrointestinal mucosa following oral administration and also via the lungs during inhalation exposure. The aqueous solubility of the test substance would allow some direct urinary excretion of the absorbed dose, but biotransformation would be expected. The fluorine and trifluoromethyl moieties are unlikely to be subject to metabolism. Ring hydroxylation would be expected to be a predominate reaction and, by analogy to trifluoromethylpyridine, would form metabolites of less toxicity. N-oxidation is feasible, although sulphate conjugation of this product would be expected to protect against its potential toxicity.
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