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EC number: - | 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:
- From 2015-12-22 to 2016-01-21
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- 2001
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Version / remarks:
- May 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Version / remarks:
- 2002
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
- Version / remarks:
- November 2000; including the most recent partial revisions.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- no
Test material
- Reference substance name:
- 1-amino-N-[6-cyano-5-(trifluoromethyl)-3- pyridyl]cyclobutanecarboxamide
- Cas Number:
- 1950587-17-3
- Molecular formula:
- C12H11F3N4O
- IUPAC Name:
- 1-amino-N-[6-cyano-5-(trifluoromethyl)-3- pyridyl]cyclobutanecarboxamide
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material: JNJ-63632283-AAA (T003665)
- Physical state: solid (powder)
- Appearance: white powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: I15HD3050
- Expiration date of the lot/batch: 2017-08-17
- Physical Description: white powder
- Purity: 98.1%
- Purity test date: 2015-10-29
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: store at room temperature (+15°C to +25 °C)
- Stability and homogeneity of the test material in the vehicle under test conditions (e.g. in the exposure medium) and during storage: The preparations (w/w) were kept at room temperature and were dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficiently for these kinds of studies.
- Stability under test conditions: not indicated
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: not indicated
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid (e.g. stock crystals ground to fine powder using a mortar and pestle):
FORM AS APPLIED IN THE TEST: liquid
OTHER SPECIFICS
- Correction factor: 1
- pH (1% in water, indicative range): 6.8 – 6.7 (determined by WIL Research Europe)
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl:WI (Han) (outbred, SPF-Quality)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: 9 female rats (nulliparous and non-pregnant), Wistar strain Crl:WI (Han) (outbred, SPF-Quality); Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx.. 8 - 9 weeks old
- Weight at study initiation: 146 - 176 grams
- Fasting period before study: animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: group housed (up to 3 animals per of the same sex and same dosing group together) in polycarbonate labeled cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) . For psychological/environmental enrichment, animals were provided with paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom), except when interrupted by study procedures/activities.
- Diet (e.g. ad libitum): ad libitum, free access to pelleted rodent diet t (SM R/M-Z from SSNIFF® Spezialdiäten GmbH,
Soest, Germany).
- Water (e.g. ad libitum): ad libitum, free access to municipal tap water via water bottles.
- Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study
- Acclimation period: at least 5 days before the commencement of dosing.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24 °C
- Humidity (%): 40-70%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 2015-12-22 To: 2016-01-21
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- propylene glycol
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 200 mg/mL and 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial preparations performed at WIL Research Europe and on test item data supplied by the Sponsor. The vehicle was chosen from (in order of preference): water (Elix) (formulation too granular), 1% aq. carboxymethyl cellulose (formulation too granular), propylene glycol (spec.gravity 1.036) (turbid solution),
polyethylene glycol 400 (spec. gravity 1.125) and corn oil (spec. gravity 0.92).
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
DOSAGE PREPARATION:
- Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing. No correction was made for purity of the test item. - Doses:
- 2000 mg/kg and 300 mg/kg (single dosage)
- No. of animals per sex per dose:
- 3 females per dose, 3 groups in total
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days (until day 15)
- Frequency of observations and weighing:
mortality/moribundity: twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings. Animals showing pain, distress or discomfort, which was considered not transient in nature or was likely to become more severe, were sacrificed for humane reasons based on OECD guidance document on humane endpoints (ENV/JM/MONO/ 2000/7). The time of death was recorded as precisely as possible;
body weights: days 1 (pre-dose), 8 and 15 and at death ( if found dead or sacrificed after Day 1).
clinical signs: at periodic intervals on the day of dosing (at least three times) (day 1) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored.
- Necropsy of survivors performed: yes, animals surviving until scheduled euthanasia were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded. - Statistics:
- No statistical analysis was performed.
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:
- At 2000 mg/kg, two animals were found dead on Day 2 and one animal was sacrificed for humane reasons on Day 2. At 300 mg/kg, one animal was found dead on Day 3.
- Clinical signs:
- other:
- Body weight:
- other body weight observations
- Remarks:
- The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
- Gross pathology:
- At 2000 mg/kg, abnormalities of the lungs (several reddish focus/foci) were found in the animal that was sacrificed for humane reasons during the study, at macroscopic post mortem examination.
At 300 mg/kg, abnormalities of the right kidney (agenesis) were found in one of the animals, at macroscopic examination. Autolysis was noted for the animals that were found dead. This was considered not toxicologically relevant.
Any other information on results incl. tables
Number of dead animals in each test group with 3 animals each:
Females 2000 mg/kg: 2/3 found dead and 1/3 sacrificed for humane reasons
Females 300 mg/kg: 1/3
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The oral LD50 value of JNJ-63632283-AAA (T003665) in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.
Based on these results:
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments),
JNJ-63632283-AAA (T003665) should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route;
- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), JNJ-63632283-AAA (T003665) should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.
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