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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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 2012-09-26 to 2012-10-19
- 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 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 1-(5'-((5S)-5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'-H-spiro(azetidine-3,1'-(2)benzofuran)-1-yl)-2-(methylsulfonyl)ethanone
- Cas Number:
- 1398609-39-6
- Molecular formula:
- C23H18Cl2F4N2O5S
- IUPAC Name:
- 1-(5'-((5S)-5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'-H-spiro(azetidine-3,1'-(2)benzofuran)-1-yl)-2-(methylsulfonyl)ethanone
Constituent 1
- Specific details on test material used for the study:
- Lot No: PF-06450567-00-0022
Purity: Not provided
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague-Dawley; Indianapolis, IN
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: 17.9 - 22.9 g (range-finding); 19.8 - 25.3 g (main test)
- Housing: Polycarbonate boxes with bedding, 1-5 per cage
- Diet: PMI Feeds, available ad libitum
- Water: Municipal water, available ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 42-91
- Air changes (per hr): 10+ air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
- IN-LIFE DATES: From: 10 Oct 12 To: 15 Oct 12
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 0.5%, 1% and 2.5% v/v in 80% acetone:20% olive oil
- No. of animals per dose:
- 5 females per dose
- Details on study design:
- PRE-SCREEN TESTS:
Healthy mice were released from quarantine prior to testing. Five females/group were selected for irritation screening to determine the three consecutive concentrations for the main test. Tested were 100% undiluted, and 50, 25 and 5% v/v dilutions of test item in acetone:olive oil. All Test group animals dosed higher than 5% died during the screening; therefore, lower doses were selected for the main test.
MAIN STUDY
- Test Item Preparation and Administration:
Five females were selected for each of three Test groups (Groups I - III). On Days 1, 2 and 3, each Test animal in its group received an open application of 25 μL of an appropriate dilution (0.5, 1 or 2.5%) of the test item to the dorsum of both ears. The Vehicle Control group (5 females) was treated in the same way as test animals, but with vehicle alone (acetone:olive oil) instead of test item dilution. The Positive Control group (5 females) was treated with 80% alpha-hexylcinnamaldehyde in acetone:olive oil. All Test and Control animals were given a two-day rest period on Days 4 and 5.
- Injection of Tritiated Methyl-Thymidine
On Day 6 of the study, all Test and Control animals were injected in the tail vein with 250 μL of 0.01 M phosphate-buffered saline, pH 7.4 at 25℃ per manufacturer, containing 20 μCi of [methyl-3H] Thymidine. Five hours after the injection, the animals were sacrificed with an overdose of CO2, the draining auricular lymph nodes were excised and pairs from each individual animal were processed.
- Body Weights and Observations:
Individual body weights were recorded on Day 1 prior to dosing, and Day 6, prior to injection. All Test and Control animals were observed daily for clinical signs of toxicity and any signs of excessive irritation at the test site.
- Criteria used to consider a positive response: stimulation index >3 - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
- Positive control results:
- Stimulation index: 4.9, positive
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 2.5
- Test group / Remarks:
- Test Group III; Test Item Concentration: 2.5%
- Parameter:
- SI
- Value:
- 2.3
- Test group / Remarks:
- Test Group II; Test Item Concentration: 1%
- Parameter:
- SI
- Value:
- 1.2
- Test group / Remarks:
- Test Group I; Test Item Concentration: 0.5%
- Cellular proliferation data / Observations:
- Four animals in Test Group I and three in Test Group II lost/failed to gain weight during the study; two animals in each Control group also lost weight.
Two Test Group III animals were found dead on Day 4; otherwise, all animals appeared normal for the duration of the study.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item produced a stimulation index of < 3 in all groups of Test animals, and is not therefore considered a sensitizer (defined as producing a positive response).
- Executive summary:
A skin sensitization study was conducted on 3 groups of 5 female mice to determine if test item possesses a significant potential to cause skin sensitization according to OECD 429. Five females were assigned to each of three groups, designated Groups I - III. The Test groups were treated with an appropriate dilution (0.5, 1 or 2.5%) in acetone:olive oil vehicle. Each animal received 25 μL to the dorsum of each ear. The animals were treated once daily for three days. After a two-day rest period, all animals were injected with tritiated methyl-thymidine in the tail vein. Five hours later, the animals were sacrificed, and the draining auricular lymph nodes removed and prepared for cell suspension and scintillation counting. A Vehicle Control group of five females was run concurrently, treated in the same manner with vehicle only instead of test item dilution. A Positive Control group of five females was also run concurrently, treated with 80% alpha-hexylcinnamaldehyde in acetone:olive oil.
The test item produced a stimulation index of < 3 in all groups of Test animals, and is not therefore considered a sensitizer (defined as producing a positive response).
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