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EC number: 204-127-4 | CAS number: 116-15-4
- 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

Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study did not reference OECD guidelines and GLP. One dose level was tested on female rats. No information on age of the animals, housing and environmental conditions. This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Metabolism of hexafluoropropene: Evidence for bioactivation by glutathione conjudate formation in the Kidney
- Author:
- Koob M, Dekant W
- Year:
- 1 990
- Bibliographic source:
- Drug Metab Dispos. 18(6):911-916
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- yes
- Remarks:
- one single dose and one sex
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Hexafluoropropene
- EC Number:
- 204-127-4
- EC Name:
- Hexafluoropropene
- Cas Number:
- 116-15-4
- Molecular formula:
- C3F6
- IUPAC Name:
- 1,1,2,3,3,3-hexafluoroprop-1-ene
- Reference substance name:
- 1-Propene, hexafluoro-
- IUPAC Name:
- 1-Propene, hexafluoro-
- Details on test material:
- Purity: 99%
Constituent 1
Constituent 2
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Source: Institut fur Versuchstierkunde (Hannover, FRG).
- Age at study initiation: No data.
- Weight at study initiation: 220-260 grams.
- Fasting period before study: No data.
- Housing: No data.
- Individual metabolism cages: Yes.
- Diet (e.g., ad libitum): ad libitum.
- Water (e.g., ad libitum): ad libitum.
- Acclimation period: No data.
ENVIRONMENTAL CONDITIONS:
- Temperature (°C): No data.
- Humidity (%): No data.
- Air changes (per hr): No data.
- Photoperiod (hrs dark/hrs light): No data.
IN-LIFE DATES: No data.
Administration / exposure
- Route of administration:
- inhalation
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: Whole body
GENERATION OF TEST ATMOSPHERE/CHAMBER DESCRIPTION:
- Exposure apparatus: Closed exposure system and HFP gas was introduced with an airtight syringe through an airtight septum. - Duration and frequency of treatment / exposure:
- 1 hr (in vivo study), 1 hr incubation (in vitro).
Doses / concentrations
- Remarks:
- Doses / Concentrations:
800 ppm (in vivo study); 1mM (in vitro).
- No. of animals per sex per dose / concentration:
- Two female rats (in vivo study). No information on number of cannulated rats. No information on number of replicates in the in vitro assay.
- Control animals:
- no
- Details on study design:
- In vivo study:
Two female rats were transferred into the closed exposure system and hexafluoropropene gas was introduced with an airtight syringe through an airtight septum to give a final concentration of 800 ppm. After 1 hour, the rats were transferred to a metabolic cage and urine was collected for 6 hours, and then extracted. Bile cannulation surgery was performed in rats. Cannulated rats were exposed to hexafluoropropene at 800 ppm for 1 hour and bile and urine were collected over 8 hours. Tap water was supplied ad libidum. Rat liver microsomes and cytosol were analyzed. Urine and bile samples were analyzed.
Enzymatic assay:
Rat liver microsomes and cytosol were prepared. Hexafluoropropene (HFP) gas (1mM) was introduced into the incubation mixture (0.1 M potassium phosphate buffer, pH 7.4, containing 0.1-0.5 mg/mL microsomal or 0.25-1 mg/mL cytosolic protein, 0.1 mM tetrasodium EDTA, and 10 mM GSH in a final volume of 2.5 mL) , with a gastight syringe. Samples were removed with a syringe through a gastight septum. In some experiments, an NADPH-generating system or 1-chloro-2,4-dinitro-benzene were included. The reactions were stopped by addition of 0.1 mL of 30 percent trichloroacetic acid. The precipitated protein was removed by centrifugation. Samples of the supernatant (0.01-0.05 mL) that were fractionated by HPLC. S-conjugates were quantified.
Separation and quantification of S-conjugates from supernatant samples were fractionated by HPLC. Conjugate concentrations from urine and bile samples were separated by HPLC and and identified by GC/MS. - Details on dosing and sampling:
- Non-cannulated rats: Urine was collected for 6 hrs.
Cannulated rats: Bile and urine were collected over 8 hrs. - Statistics:
- Results were expressed as mean +/- standard deviation.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- Non-cannulated rats: Urinary excretion of N-acetyl-hexafluoro-propyl-cysteine (N-Ac-HFPC) amounted to 10 +/- 3 percent of the dose of HFP introduced into the exposure system (three replicates). In the time interval from 6 hr to 24 hr, less than 1 percent of the HFP dose could be recovered in urine.
Cannulated rats: Of the administered HFP dose, 8 +/- was recovered as N-AC-HFPC in urine (three replicates).
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- In vitro: Incubations of HFP with liver and kidney subcellular fractions in the presence of GSH resulted in the formation of two metabolites, identified as S-hexafluoropropyl-glutathione (HFPG) and S-pentafluoropropenyl-glutathione (PFPG).
In vivo: a peak with identical retention time and mass spectrum as the synthetic mercapturic acid N-Ac-HFPC methyl ester was identified. The mass spectometric fragmentation of the metabolite definitively identifies N-Ac-HFPC as a urinary metabolite of hexafluoropropene in the rat. The results suggested that hexafluoropropene may be exclusively metabolized by GST in vivo in an addition-reaction to give HFPG.
Hexafluoropropene is metabolized by GST to HFPG and PFPG. Oxidative metabolism could not be demonstrated. The GSH S-conjugates are structural analogues to GSH S-conjugates biosynthesized from other nephrotoxic haloalkenes. The identification of GSH S-conjugates as metabolites of hexafluoropropene thus suggests that these mechanisms also are responsible for hexafluoropropene nephrotoxicity. Collected bile contained PFPG as the only detectable metabolite. Because N-Ac-PFPC or other PFPG metabolites could not be detected in the urine, it is possible that PFPG formed in the liver is not translocated to the kidney to be processed to the corresponding mercapturic acid. The possibility of complete metabolism of PFPG by the enzymes of the mercapturic acid pathway and by b-lyase could not be ruled out. However, the results support the speculation that intrarenal conjugation of hexafluoropropene with GSH may be an important step in the bioactivation of hexafluoropropene.
The results support the speculation that intrarenal conjugation of hexafluoropropene with GSH may be an important step in the bioactivation of hexafluoropropene. HFPG formed in the kidney could be processed by gamma-glutamyltranspeptidase and dipeptidases to the coresponding cysteine S-conjugate, which is metabolized by renal cystein conjudate b-lyase, to give an electrophilic intermediate, most likely a thionoacyl fluoride.
The above hypotheses were supported by analytical results.
Any other information on results incl. tables
Applicant's summary and conclusion
- Conclusions:
- The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
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