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EC number: 841-499-2 | CAS number: 1340593-59-0
- 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
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Endpoint summary
Administrative data
Description of key information
In an acute oral toxicity study (acute toxic class method, OECD 423), three groups of fasted, 8-9 weeks old, female Wistar rats (3 rats/step) were given a single oral dose of (2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl]propan-2-ol in corn oil at 300 (step 2 and 3) or 2000 mg/kg bw (step 1) and were observed for 14 days. Based on the results and in accordance with OECD guideline 423, the LD50 cut-off value was determined to be 500 mg/kg bw. Thus, the substance meets the criteria of the CLP regulation 1272/2008 for being classified as Acute Tox. 4, H302.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2020-03-11 to 2020-06-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- adopted 17 December 2001
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- no
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: In order to get the test item in a solution or suspension, which is applicable to the animals, corn oil (Sigma, lot no. MKCK6411, expiry date: 16.05.2020) was evaluated as vehicle and was considered to be adequate. This vehicle was chosen due to its non-toxic characteristics. Homogeneity of the test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before each dose administration. For all animals of the first step, 2.0019 g of the test item was diluted with the vehicle to gain a final volume of 10 mL and to achieve a dose of 2000 mg/kg body weight at a dose volume of 10 mL/kg body weight. For all animals of the second and third step, 0.3014 g and 0.3007 g, respectively, of the test item was diluted with the vehicle to gain a final volume of 10 mL and to achieve a dose of 300 mg/kg body weight at a dose volume of 10 mL/kg body weight. The dose formulations were made shortly before each dosing occasion. - Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8–12 weeks
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Fasting period before study: 16 h
- Diet (e.g. ad libitum): ad libitum, free access to Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): ad libitum, free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- VEHICLE
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): MKCK6411, expiry date 2020-05-16
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw - Doses:
- Step 1: 2000 mg/kg bw
Step 2, 3: 300 mg/kg bw - No. of animals per sex per dose:
- Step 1: three females
Step 2, 3: six females in total - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the administration) and on days 8 and 15. The surviving animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
- Necropsy of survivors performed: yes, at the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of 250-400 mg/kg bw. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes.
- Clinical signs: A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. - Statistics:
- n.a.
- Preliminary study:
- n.a.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50 cut-off
- Effect level:
- 500 mg/kg bw
- Based on:
- test mat.
- Mortality:
- All animals treated with the test item at a dose of 2000 mg/kg bw had to be euthanised for ethical reasons on day 5 (animal no. 2) or day 9 (animal no. 1 and 3). At 300 mg/kg bw all treated nimals survived until the end of the study.
- Clinical signs:
- other: The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection and ataxia. The clinical signs persisted until the end of the observation period in all animals treate
- Gross pathology:
- Macroscopic findings of surviving animals (300 mg/kg bw): enlarged liver
Macroscopic findings of animals not having survived until the end of the observation period (2000 mg/kg bw): enlarged adrenal glands - Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- In an acute oral toxicity study in rats conducted according to OECD 423, mortality occurred at the limit dose of 2000 mg/kg bw. At 300 mg/kg bw, no mortality was observed. Hence, the LD50 cut off value is 500 mg/kg bw and classification as Acute Tox. 4 , H302 is warranted in accordance with CLP Regulation 1272/2008.
- Executive summary:
In an acute oral toxicity study (acute toxic class method, OECD 423), groups of fasted, 8-9 weeks old female Wistar rats (3 rats/step) were given a single oral dose of the test item (99.99% purity) in corn oil. In a first step, three females received 2000 mg/kg bw and all animals treated with this dose had to be euthanised for ethical reasons on day 5 (animal no. 2) or day 9 (animal no. 1 and 3). In the following steps 2 and 3, 6 females in total received 300 mg/kg bw. All animals treated with this dose survived the 14-day observation period without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. Necropsy of the surviving rats at 300 mg/kg bw revealed enlarged livers. Based on the results from this study, the oral LD50 cut off value in rats is considered to be 500 mg/kg bw and classification as Acute Tox. 4 , H302 is warranted in accordance with CLP Regulation 1272/2008.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 500 mg/kg bw
- Quality of whole database:
- GLP guideline study
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In an acute oral toxicity study (acute toxic class method, OECD 423), three groups of fasted, 8 - 9 weeks old, female Wistar rats (3 rats/step) were given a single oral dose of the test item (99.9 % purity) in corn oil at 300 (step 2 and 3) or 2000 mg/kg bw (step 1) and were observed for 14 days. In a first step, three females received 2000 mg/kg bw and all animals treated with this dose had to be euthanised for ethical reasons on day 5 (animal no. 2) or day 9 (animal no. 1 and 3). In the following steps 2 and 3, 6 females in total received 300 mg/kg bw. All animals treated with this dose survived the 14-day observation period without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. Necropsy of the surviving rats at 300 mg/kg bw revealed enlarged livers. Based on the results from this study, the oral LD50 cut off value in rats is considered to be 500 mg/kg bw and classification as Acute Tox. 4 , H302 is warranted in accordance with CLP Regulation 1272/2008.
Justification for classification or non-classification
Based on the available data, (2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl]propan-2 -ol classification for acute toxicity (Acute Tox.4, H302) is warranted in accordance with CLP Regulation 1272/2008. The oral LD50 cut-off value was determined to be 500 mg/kg bw.
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