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EC number: 922-147-8 | 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:
- 2011-10-06 to 2011-11-03
- 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 guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- methyl (1R,2R,4S)-2-[(hex-5-en-1-yl)(methyl)carbamoyl]-4-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)cyclopentane-1-carboxylate
- EC Number:
- 922-147-8
- Cas Number:
- 1042695-87-3
- Molecular formula:
- C32H41N3O5S
- IUPAC Name:
- methyl (1R,2R,4S)-2-[(hex-5-en-1-yl)(methyl)carbamoyl]-4-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)cyclopentane-1-carboxylate
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material (as cited in study reports): JNJ-39125593-AAA (T003019)
- Physical state: solid
- Appearance: white powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Batch number: RT003019PFP201
- Expiration date of the lot/batch: 06 July 2011 (retest date)
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (15-25°C) protected from light
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: no data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was used as supplied. A conversion factor of 1.02 was applied and all formulations were prepared on the day of dosing at the required concentration(s).
A vehicle trial was conducted and JNJ-39125593-AAA showed the following:
At 100% w/v, the material was too bulky to achieve a formulation in any vehicle tested and therefore this concentration was not suitable for use on this study.
At 50% w/v the formulations in all vehicles were thick pastes or too bulky to formulate and not suitable for dosing.
At 25% w/v, the formulation in acetone:olive oil (4:1 v/v) was an off white suspension, the formulation in dimethylformamide was a very fine pale brown suspension, the formulation in methyl ethyl ketone was a clear pale
brown solution, the formulation in propylene glycol was a very thick off white suspension and the formulation in dimethylsulphoxide gave a thick off white suspension. With the exception of the formulation in propylene
glycol, all of these formulations were suitable for dosing.
At 10% w/v, the formulation in acetone:olive oil (4:1 v/v) was a clear yellow solution, the formulation in dimethylformamide was a clear pale brown solution, the formulation in propylene glycol was a thick of white, bitty
suspension and the formulation in dimethylsulphoxide was an off white suspension. All of these formulations were suitable for dosing. Based on the results at 25% w/v, methyl ethyl ketone was chosen as the vehicle for this study.
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA/Ca
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: 24 healthy female CBA/Ca mice; Charles River UK Ltd
- Age prior to dosing on day 1: 8-12 weeks
- Weight prior to dosing on day 1: 18-21.8 grams
- Housing: inside a barriered rodent facility, designed and operated ro minimise the entry of external biologial and chemical agents and to minimise the transference of such agents between rooms; pair housed in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding, additionally Nestlest and a plastic shelter were included for environmental enrichment.
- Diet (e.g. ad libitum): the animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet). This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent. Each batch of diet was analysed routinely by the supplier for various nutritional components and chemical and microbiological contaminants
- Water (e.g. ad libitum): potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes. The quality of the water supply is governed by regulations published by the Department for Environment, Food and Rural Affairs. The results of these various analyses did not provide evidence of contamination.
- Acclimation period: at least 6 days prior to the start of the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23°C
- Humidity (%): 40-70%
- Air changes (per hr): the animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to the atmosphere and re-circulated.
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- methyl ethyl ketone
- Remarks:
- 25% w/v
- Concentration:
- 0, 5, 10 and 25% (w/v)
- No. of animals per dose:
- Preliminary investigation: 2 females/group
Main study: 4 females/group; 3 test groups and 1 control group - Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: no data
- Irritation: No dermal irritation was observed on the ears of any mouse on Days 1 to 6.
- Systemic toxicity: There were no deaths and no signs of ill health or toxicity observed during this study.
At 10% w/v, greasy fur on the head was noted following each dosing occasion. In addition, white dose residue on the ears was seen post dose from Day 2 and on Days 4 and 5. All signs had recovered by Day 6.
At 25% w/v, greasy fur on the head was noted following each dosing occasion. In addition, white dose residue on the ears was seen post dose from Day 1, prior to dosing from Day 2 and on Days 4 to 6.
- Ear thickness measurements: There was no evidence of an effect of treatment on ear thickness.
- Erythema scores: 0 in all animals for day 1 to 6
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Groups of four female mice were treated at one of three concentrations of the test substance. The mice were treated by daily application of 25 µl of the appropriate concentration of the test substance to the dorsal surface of each ear for three consecutive days (days 1-3). The test substance was applied using an automatic micropipette and was spread over the entire dorsal surface of the ear using the tip of the pipette. Further groups of four mice received the vehicle alone or the positive control substance in the same manner.
- Criteria used to consider a positive response: results for each treatment group were expressed as the Stimulation Index (S.I.). This was derived by dividing the mean DPM/mouse for each treated group or the positive control group by the mean DPM/mouse in the vehicle control group. If the SI is 3 or more, the test substance is regarded as a skin sensitizer. The positive control group is expected to give an SI of 3 or more to demonstrate the validity of the study.
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: If the SI is 3 or more, the test substance is regarded as a skin sensitizer.
TREATMENT PREPARATION AND ADMINISTRATION:
The test substance, was prepared for administration as a series of graded concentrations in the vehicle, by direct dilution. The test substance was used as supplied. A conversion factor of 1.02 was
applied and all formulations were prepared on the day of dosing at the required concentration(s). The absorption of the test substance was not determined. Determination of the homogeneity, stability and purity of the test substance or test substance formulations were not undertaken as part of this study.
The mice were treated by daily application of 25 µL of the appropriate concentration of the test substance to the dorsal surface of each ear for three consecutive days (Days 1-3). The test substance was applied using an automatic micropipette and was spread over the entire dorsal surface of the ear using the tip of the pipette. Further groups of four mice received the vehicle alone or the positive control substance in the same manner. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- No statistical analysis performed.
Results and discussion
- Positive control results:
- The SI for the positive control substance hexyl cinnamic aldehyde (HCA), was 12.5 which demonstrates the validity of this study.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 1.4
- Test group / Remarks:
- 5% w/v group
- Parameter:
- SI
- Value:
- 1.7
- Test group / Remarks:
- 10% w/v group
- Parameter:
- SI
- Value:
- 2.8
- Test group / Remarks:
- 25% w/v group
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
5% w/v group: DPM/node: 730.13 (8 lymph nodes)
10% w/v group: DPM/node: 865.88 (8 lymph nodes)
25% w/v group: DPM/node: 1429.06 (8 lymph nodes)
DETAILS ON STIMULATION INDEX CALCULATION
The SI (test/control ratios) obtained for 5, 10 and 25% w/v were 1.4, 1.7 and 2.8 respectively. As a SI of 3 or more was not recorded for any of the concentrations tested, is not considered to have the potential to cause skin sensitization.
EC3 CALCULATION
Based on the results of this study the EC3 value was reported to be greater than the highest concentration tested (25% w/v).
MORTALITY AND CLINICAL OBSERVATIONS:
There were no deaths and no signs of ill health or toxicity observed during this study.
Greasy fur on the head was noted for all animals following each dosing occasion and also prior to dosing on Days 2 and 3 and on Day 4 for Group 7 (positive control), this was related to unoccluded dermal administration of a
liquid formulation/vehicle and not an effect of the test substance. In addition, white dose residue on the ears was seen post-dose on Days 2 and 3 in Groups 5 and 6 (10 and 25% w/v) and post-dose on Day 1, prior to dosing
on Day 3 and on Days 4, 5 and 6 for Group 6.
DERMAL REACTIONS
No signs of dermal irritation were seen on the ear during the study.
BODY WEIGHTS
There was no indication of an effect of treatment on bodyweight gain. A loss in bodyweight was noted for two mice (Nos. D18 and D24) over the study period, however, a small loss in bodyweight is not uncommon in young laboratory mice and is not considered to be an effect of treatment.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item was not regarded as a potential skin sensitizer.
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