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EC number: 471-480-0 | CAS number: 1645-83-6
- 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
Endpoint summary
Administrative data
Description of key information
Several repeated dose toxicity studies are available (2-weeks, 4-weeks and 13-weeks of exposure). No toxicity was observed in male or female rats exposed to concentrations up to 5 000 ppm for 6 hours/day for 2, or 13 weeks, or concentrations up to 10 000 ppm following 4 weeks of exposure.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- 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:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: mean weights 252 g (males) and 176 g (female)
- Fasting period before study: none
- Housing: macrolon cages with wood shaving beding
- Diet (e.g. ): ad libitum (overnight fast prior to necropsy)
- Water (e.g. ):ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 36-46 (one day humidity in high dose group was > 70% for less than 5 minutes- quickly fixed)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: March 2007 To: June 2007 - Route of administration:
- inhalation: gas
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:cylindrical PVC column with a volume of ~ 70 litres surrounded by a transparent hook. The test atmosphere was introduced at the bottom and exhausted at the top
- Method of holding animals in test chamber:
- Source and rate of air: at least 1 litre/min
- Temperature, humidity in air chamber: 20 - 24 °C; 30 - 70 % humidity
- Air flow rate: at least 1 litre/min
TEST ATMOSPHERE
- Brief description of analytical method used: total carbon analysis
- Samples taken from breathing zone: yes
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- total carbon analysis
- Duration of treatment / exposure:
- 6 hours day
- Frequency of treatment:
- 5 days a week
- Dose / conc.:
- 1 500 ppm (analytical)
- Remarks:
- Group 2: Low dose.
- Dose / conc.:
- 5 000 ppm (analytical)
- Remarks:
- Group 3: Mid dose.
- Dose / conc.:
- 15 000 ppm (analytical)
- Remarks:
- Group 4: High dose.
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: 15000 ppm (1.5 %) was chosen due to the effects observed in the range finding study
- Post-exposure recovery period in satellite groups: none - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes (daily)
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for per group determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at scheduled necropsy
- Anaesthetic used for blood collection: Yes (identity) -Nembutal
- Animals fasted: Yes
- How many animals: all survivors
- Parameters listed in OECD guideline were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at scheduled necropsy
- Animals fasted: Yes
- How many animals: all survivors
- Parameters listed in OECD guideline were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: no - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - those organs listed in the guideline plus nose (6-levels), larynx (3 levels), trachea (3 levles including bifurcation), and each lung lobe at 1 level. - Statistics:
- Data were evaluated by the appropriate statistical test (one-way analysis of variance followed by Dunnett's multiple comparison test, one-way analyis of variance (ANOVA) followed by Dunn't multiole comparison testes, Krisckal-Wallis nonparametric Anova followed by Mann-Whitney U-tests, Fischers exact probability test.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Concentration of the monocytes and thrombocytes were increased in male animals of the high concentration group.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased AST in high dose males, increased urea in high dose females
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Multifocal mononuclear cell infiltrates, often accompanied by myocardial degeneration (increased eosinophilia and pyknotic nuclei). A silver stain for reticulum did not provide evidence for fibrosis in high dose male and female
- Histopathological findings: neoplastic:
- no effects observed
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 5 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: multifocal mononuclear cell infiltrates in the heart of the 15000 ppm males and females.
- Key result
- Critical effects observed:
- not specified
- Conclusions:
- Overall, exposure of rats to 1500, 5000 or 15000 ppm HFO-1234ze for 6 h/day, 5 days/week for 63 or 64 exposure days over a 91 - 92 day period did result in slight adverse effects in animals of the high concentration group only. In the present subchronic inhalation toxicity study, the mid concentration level of 5000 ppm was therefore considered to be a No-Observed-Adverse-Effect-Concentration (NOAEC) for male and female rats.
- Executive summary:
Overall, exposure of rats to 1500, 5000 or 15,000 ppm HFO-1234ze for 6 h/day, 5 days/week for 63 or 64 exposure days over a 91-92 day period did result in slight adverse effects in animals of the high concentration group only. In the present subchronic inhalation toxicity study, the mid concentration level of 5000 ppm was therefore considered to be a No-Observed-Adverse-Effect-Concentration (NOAEC) for male and female rats.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 23 300 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- There are 3 repeated dose toxicity studies available (2-week, 4-week and 13-week exposure duration). All studies were performed recently and according to relevant Guidelines. All studies are considered bo be of good quality (K1).
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In the 2 -week study, rats were exposed to 0, 5000, 20000 and 50000 ppm. The NOEC in that study was 5000 ppm. In the 4 -week study, rates were exposed to 0, 1000, 5000, 10000 and 15000 ppm leading to a NOEC of 10000 ppm. Finally in the 13 -week study, rats were exposed to 0, 1500, 5000 and 15000 ppm leading to a NOEC of 5000 ppm.
The multifocal mononuclear cell infiltrates in the heart of both sexes in the 13 -week study was only seen at 15000 ppm and was predominately characterized as slight. Similar effects were observed in the 2 - and 4 - week studies. Increased exposure duration however did not appear to increase the incidence or severity of the effects seen in the heart. This statement was confirmed by the observations made in the 2 -generation reproductive toxicity study. Additionally, fibrosis was not observed in the 90 day (13 -week) study indicating this is not a progressive lesion. Based on these results, 15 000 ppm was considered as the LOAEC and 5 000 ppm was considered the NOEC for the 13 -week exposure study. This NOEC is used further on in the dossier for risk assessment purposes. However, when considering the lack of progression of the heart lesion, the NOEC of 10 000 ppm seen in the 4 -week study could represent a more accurate NOEC for repeat exposures to HFO-1234ze.
Repeated dose toxicity: inhalation - systemic effects (target organ) cardiovascular / hematological: heart
Justification for classification or non-classification
Repeated inhalation exposure to HFO-1234ze resulted in cardiac effects (multifocal infiltrates) which did not increase in incidence or severity with prolonged exposure. The no observed effect level in the 13 -week study is 5000 ppm and for the 4 - week study 10 000 ppm. Based on the available information classification upon repeated exposure is not warranted according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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