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EC number: 606-374-7 | CAS number: 197706-51-7
- 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 2017-08-10 to 2018-08-31
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- no
Test material
- Reference substance name:
- (+)-(S,R)-6-fluoro-3,4-dihydro-2-(2-oxiranyl)-2H-1-benzopyran
- EC Number:
- 606-374-7
- Cas Number:
- 197706-51-7
- Molecular formula:
- C11H11FO2
- IUPAC Name:
- (+)-(S,R)-6-fluoro-3,4-dihydro-2-(2-oxiranyl)-2H-1-benzopyran
- Test material form:
- other: wax
- Details on test material:
- Physical state: wax form
Appearance: clear, viscous, wax
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Janssen Pharmaceutica N.V., I17EB1781
- Expiration date of the lot/batch: 26 April 2018 (retest date)
- Purity correction factor: 1.13
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: No data.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: 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. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test item.
Before sampling the test item was heated in a warmth cabinet at 60ºC for approximately 3 days. In order to obtain homogeneity, the test item preparations were heated in a water bath with a maximum temperature of 61.3ºC for a maximum of 16 minutes. The test item formulations were allowed to cool to a temperature of maximally 40ºC prior to dosing.
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Wistar strain Crl:WI (Han) (outbred, SPF-Quality); Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10-11 weeks old
- Weight at study initiation: 171 - 194 grams
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test item. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (ad libitum): Free access to pelleted rodent diet
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C; the actual daily mean temperature during the study period was 21 - 22°C
- Humidity (%): 40 to 70; the actualy daily mean relative humidity was 50 - 72%.
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Remarks:
- 400
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 174 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 Charles River Den Bosch and on test item data supplied by the Sponsor. The vehicle was chosen from (in order of preference): water (Elix) (test item did not dissolve), 1% aq. carboxymethyl cellulose (test item did not dissolve), propylene glycol (spec.gravity 1.036) (test item did not dissolve), polyethylene glycol 400 (spec. gravity 1.125) (yellow clear solution) and corn oil (spec. gravity 0.92) (yellow clear solution).
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
DOSAGE PREPARATION (if unusual):
- 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 sufficient for these kinds of studies.
- Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test item. Before sampling the test item was heated in a warmth cabinet at 60ºC for approximately 3 days. In order to obtain homogeneity, the test item preparations were heated in a water bath with a maximum temperature of 61.3ºC for a maximum of 16 minutes. The test item formulations were allowed to cool to a temperature of maximally 40ºC prior to dosing. - Doses:
- 1770 mg/kg bw
- No. of animals per sex per dose:
- 3 females per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy of survivors performed: yes, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded. - Statistics:
- No statistical analysis was performed.
Results and discussion
Effect levels
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 1 770 mg/kg bw
- Based on:
- test mat.
- Mortality:
- One animal was found dead on Day 2.
- Clinical signs:
- Lethargy, flat and hunched posture, uncoordinated movements, piloerection, salivation, and/or ptosis were noted for the animals between Days 1 and 3, with piloerection and hunched posture reappearing on Day 7 for one animal. Additionally, slow breathing, shallow respiration and hypothermia were observed on Day 1 for the animal that died during the study.
- Body weight:
- 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:
- Several dark red foci on the thymus were found in the animal that died during the study, at macroscopic post mortem examination. Additionally, beginning autolysis was noted for the animal that died during the study, which was considered not to be test item related. No further macroscopic findings were noted for the animals.
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The oral LD50 value of T001597 in Wistar rats was established to exceed 1770 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 (2017) (including all amendments), T001597 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 items and mixtures (including all amendments), T001597 should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.
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