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Diss Factsheets
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EC number: 951-814-6 | CAS number: -
- 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:
- 20 August - 9 September 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- GLP compliance:
- not specified
- Test type:
- acute toxic class method
- Limit test:
- no
Test material
- Reference substance name:
- 4-(6-{3,6-diazabicyclo[3.1.1]heptan-3-yl}pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile
- Molecular formula:
- C22H24N6O2.[2]H2O4S
- IUPAC Name:
- 4-(6-{3,6-diazabicyclo[3.1.1]heptan-3-yl}pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile
- Test material form:
- solid: particulate/powder
- Details on test material:
- Batch (Lot) Number: 18-547.25-002
Physical Description: White powder
Storage Conditions: Kept in a room temperature area, protected from light
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Justification for Test System and number of animals:
The Sprague Dawley rat was chosen as the animal model for this study as it is an accepted rodent species for preclinical toxicity testing by regulatory agencies. A total of 13 male and 13 female Sprague Dawley rats were received on 20 Aug 2019.
Six days were allowed between receipt of the animals and the start of treatment to accustom the animals to the laboratory environment. Each animal was uniquely identified using a subcutaneously implanted electronic identification chip.
Housing:
On arrival, animals were individually housed until randomization. Following, randomization, animals were socially housed in polycarbonate cages containing appropriate bedding equipped with an automatic watering valve.
Selection, Assignment, Replacement, and Disposition of Animals:
Prior to randomization procedures, the animals were weighed. Animals determined to be suitable as test subjects were assigned to groups by a stratified randomization scheme designed to achieve similar group mean body weights. Males and females were randomized separately.
Initial age: 8 weeks
Weight at the Initiation of Dosing: Males: 206 to 245 g.
Females: 149 to 167 g.
Environmental Conditions:
The animal room environment and photoperiod were controlled (targeted conditions: temperature 20C to 26C, humidity 30% to 70%, 12 hours light and 12 hours dark, except during designated periods). The overall average temperature and relative humidity ranges during the study were 21°C and 53% to 56%, respectively.
Food:
PMI Nutrition International Certified Rodent Chow No. 5CR4 was provided ad libitum throughout the study, except during designated procedures.
Maximum allowable concentrations of contaminants in the diet were controlled and routinely analyzed by the manufacturers.
Water:
Municipal tap water, purified by reverse osmosis and exposed to ultraviolet irradiation, was freely available. Periodic analysis of the water was subcontracted to management-authorized analytical laboratories. The analytical results are retained in the archives of CR-SPV .It was considered that there were no known contaminants in the dietary materials that could interfere with the objectives of the study.
Veterinary Care:
Veterinary care was available throughout the study; however, no veterinary examinations or medicinal treatments were administered during the study.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Reverse Osmosis Deionized (RODI) water
- Details on oral exposure:
- Administration of Test item:
On the day prior to dosing the animals chosen for use on the study were weighed and fasted. On Day 0, the test article was administered orally as a single dose (5, 50, 300, and 2000 mg/kg, 10 mL/kg) to rats (3/sex/group) using a syringe attached to a gavage cannula. Individual doses were calculated based on the animal's fasted (Day 0) body weight. - Doses:
- 5 mg/kg (group 1), 50 mg/kg (group 2), 300 mg/kg (group 3), 2,000 mg/kg (group 4)
- No. of animals per sex per dose:
- 3/sex/group
- Control animals:
- no
- Details on study design:
- In-life Procedures, Observations, and Measurements
Mortality/Moribundity Checks:
The animals were observed for general health/mortality and moribundity at least twice daily, at least once in the morning and at least once in the afternoon, throughout the study.
Clinical observations:
Each animal was removed from the cage and observed in detail a minimum of 2 times on Day 0 (postdose), with the first observation within approximately 30 minutes after dosing, and daily thereafter (Days 1 to 14).
Body Weights:
Individual body weights were recorded for all animals prior to fasting, prior to dosing (Day 0), and on Days 7 and 14. Animals found dead were also weighed.
Terminal Procedures:
For the animals that died on study, a necropsy was conducted. The animals were refrigerated to minimize autolysis. Animals surviving until scheduled euthanasia were weighed, euthanized by carbon dioxide inhalation, and discarded without examination. Animals that died on study were subjected to a complete necropsy examination, which included evaluation of the carcass and musculoskeletal system; all external surfaces and orifices; cranial cavity and external surfaces of the brain; and thoracic, abdominal, and pelvic cavities with their associated organs and tissues. No tissues were retained. - Statistics:
- Body weight means and standard deviations were calculated separately for males and females for each limit level administered.
The LD50 was estimated as indicated below:
< 50% mortality: LD50 was estimated as greater than the administered dose.
= 50% mortality: LD50 was estimated as equal to administered dose.
> 50% mortality: LD50 was estimated as less than the administered dose.
Results and discussion
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 300 - < 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Mortality occurred in animals administered 2000 mg/kg. Following dose administration of 2000 mg/kg on Day 0, 1/3 males was found dead and 2/3 females were found dead; on Day 3, 1/3 males were found dead. The remaining male and female administered 2000 mg/kg and all animals administered ≤ 300 mg/kg survived to scheduled euthanasia.
- Clinical signs:
- other: Test article-related clinical observations in animals administered 2000 mg/kg included abnormal breathing, erected fur, partially closed eyes, and fur staining. No test articlerelated clinical observations were noted in animals administered ≤300 mg/kg. I
- Gross pathology:
- A gross necropsy examination was performed for all found dead animals that were administered 2000 mg/kg. There were no gross necropsy findings noted for the animals.
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The oral LD50 value of Intermediate 3532670 in Sprague-Dawley rats was established to be within the range of 300-2,000 mg/kg/bw.
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