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EC number: 821-117-0 | CAS number: 1082745-49-0
- 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
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 - 21 September 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- no
Test material
- Reference substance name:
- 5-Amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carbonitrile
- EC Number:
- 821-117-0
- Cas Number:
- 1082745-49-0
- Molecular formula:
- C9H12N4O
- IUPAC Name:
- 5-Amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carbonitrile
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:WI(Han)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TST ANIMALS
- Animals chosen for this study were selected from a supply of healthy nulliparous and nonpregnant
female Crl:WI(Han) rats obtained from Charles River (UK) Ltd.
- bodyweights were in the range 173 to 196 g and they were approximately eight to twelve weeks of age prior to dosing
(Day 1)
CONDITIONS:
- Animals were housed inside a barriered rodent facility (Building F21, Room 044/045)
- The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1
Maintenance Diet), except for overnight prior to and approximately four hours after dosing
-The temperature and relative humidity controls were set to maintain the range of 19 to 23C and 40 to 70%
respectively
-Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per
24 hours.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Hydroxyethylcellulose (Natrosol 250) 0.5%.
- Details on oral exposure:
- The appropriate dose volume of the test substance was administered to each rat by oral
gavage using a plastic syringe and plastic catheter - Doses:
- 300 mg/kg and 2000 mG/kg bodyweight
- No. of animals per sex per dose:
- 300 mg/kg: 6 female; 2000 mg/kg: 3 female
- Control animals:
- no
- Details on study design:
- - Cages of rats were checked at least twice daily for any mortalities
-Animals were observed soon after dosing and at frequent intervals for the remainder of
Day 1. On subsequent days, surviving animals were observed once in the morning and again
at the end of the experimental day (with the exception of Day 15 - morning only). The nature
and severity, where appropriate, of the clinical signs and the time were recorded at each
observation
- The weight of each rat was recorded on Days 1 (prior to dosing), 2, 8 and 15 or at death.
Individual weekly bodyweight changes and group mean bodyweights were calculated.
Results and discussion
Effect levels
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 300 - < 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- All females dosed at 2000 mg/kg died, one on Day 1, and two females on Day 2. Clinical
signs seen from approximately 30 minutes after dosing comprised unsteady gait, underactive
behaviour, reduced body tone, fast breathing, flat posture, lachrymation, irregular breathing
and unresponsive behaviour in all three females, cold to touch, rales/noisy breathing and
shallow breathing in two females with gasping and piloerection seen in one female. A loss in
bodyweight was noted for two decedents. Macroscopic examination of the decedents
revealed congestion of the subcutaneous tissue and lungs, pallor of the liver, spleen and
kidneys, atrophy of the heart and caecum, red or yellow fluid contents of the stomach along
the alimentary tract and solid black contents of the caecum. - Clinical signs:
- other: There were no clinical signs of reaction to treatment in surviving females throughout the study.
- Gross pathology:
- Macroscopic examination of the surviving animals revealed atrophy of the stomach in one
female (X6) dosed at 300 mg/kg. No other abnormalities were noted in any surviving animal
at the macroscopic examination at study termination on Day 15.
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The acute median lethal oral dose (LD50) to rats of BI 409306 Pyrazol was demonstrated to be between 300 and 2000 mg/kg bodyweight.
- Executive summary:
SUMMARY
The study was performed to assess the acute oral toxicity of BI 409306 Pyrazol (a
pharmaceutical intermediate), to the rat.
Two groups of three fasted female rats received a single oral gavage dose of the test
substance, formulated in Hydroxyethylcellulose (Natrosol 250) 0.5%, at a dose level of
300 mg/kg bodyweight. As results at this dose level indicated the acute (median) lethal oral
dose of the test substance to be greater than 300 mg/kg bodyweight, in compliance with the
study guidelines a further group of three fasted females was similarly dosed at 2000 mg/kg
bodyweight to complete the study.
RESULTS
All females dosed at 2000 mg/kg died, one on Day 1, and two females on Day 2. Clinical
signs seen from approximately 30 minutes after dosing comprised unsteady gait, underactive
behaviour, reduced body tone, fast breathing, flat posture, lachrymation, irregular breathing
and unresponsive behaviour in all three females, cold to touch, rales/noisy breathing and
shallow breathing in two females with gasping and piloerection seen in one female. A loss in
bodyweight was noted for two decedents. Macroscopic examination of the decedents
revealed congestion of the subcutaneous tissue and lungs, pallor of the liver, spleen and
kidneys, atrophy of the heart and caecum, red or yellow fluid contents of the stomach along
the alimentary tract and solid black contents of the caecum.
There were no clinical signs of reaction to treatment in surviving females throughout the
study.
A loss in bodyweight was noted for one surviving female (X5) on Day 8. A notably low
bodyweight gain was noted for one surviving female (X2) dosed at 300 mg/kg on Day 15.
All other surviving animals were considered to have achieved satisfactory bodyweight gains
throughout the study.
Macroscopic examination of the surviving animals revealed atrophy of the stomach in one
female (X6) dosed at 300 mg/kg. No other abnormalities were noted in any surviving animal
at the macroscopic examination at study termination on Day 15.
CONCLUSION
The acute median lethal oral dose (LD50) to rats of BI 409306 Pyrazol was demonstrated to
be between 300 and 2000 mg/kg bodyweight.
BI 409306 Pyrazol is included in Category 4 >300-2000, according to the Globally
Harmonised System (GHS), (UNITED NATIONS, 2005).
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