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EC number: 917-473-2 | CAS number: 188416-34-4
- 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 18 June to 2 July 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study run to a method comparable with current guidelines and to GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (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:
- 188416- 34-4
- IUPAC Name:
- 188416- 34-4
- Reference substance name:
- (2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)- 10- camphorsulphonate
- IUPAC Name:
- (2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)- 10- camphorsulphonate
- Details on test material:
- - Analytical purity: 94.0%
- Lot/batch No.: 03207003
Constituent 1
Constituent 2
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Netherlands B.V. Postbus 6174 NL-5960 AD Horst/ The Netherlands
- Age at study initiation: 8-12 weeks (beginning of acclimatization period)
- Weight at study initiation: 14.5-16.4 g (beginning of acclimatization period)
- Housing: Housed individually in Makrolon type-2 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, batch no.84/02 mouse maintenance diet available ad libitum. Results of analyses for contaminants are archived at RCC.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum. Results of representative bacteriological, chemical and contaminant analyses are archived at RCC.
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3℃
- Humidity (%): relative humidity 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour fluorescent light /12 hour dark cycle with at least 8 hours music during the light period.
Study design: in vivo (LLNA)
- Vehicle:
- other: Ethanol: water, 7:3 (v/v)
- Concentration:
- The test item at concentrations of 5%, 10% and 25% (w/v) in ethanol: water, 7:3(v/v)
- No. of animals per dose:
- Number of animals for the pre-test (non-GLP): 2 females
Number of animals for the main study: 20 females (reserve animals will be used as needed and listed in raw data and report)
Number of animals per group: 5 females (nulliparous and non-pregnant)
Number of test groups: 3
Number of negative control: 1 - Details on study design:
- MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Test system: Mice, CBA/CaOlaHsd
- Criteria used to consider a positive response: --First, that exposure to at least one concentration of the test item resulted in an incorporation of HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the STIMULATION INDEX (S.I.).
--Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was placed into a volumetric flask on a tared Mettler balance and the vehicle was quantitatively added. The weight dilutions were prepared individually using a magnetic stirrer as homogenizer. Homogeneity of the test item in the vehicle was maintained during treatment with the magnetic stirrer.
1) Topical application
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 5%, 10% and 25% (w/v) in ethanol:water, 7:3 (v/v). The application volume, 25 μl, was spread over the entire dorsal surface (ø~8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals). A hair dryer was used to dry the ear's surface as quickly as possible to avoid loss of test item applied.
2) Administration of H-Methyl Thymidine
H-methyl thymidine was purchased from Amersham International (Amersham product code no. TRA 310; specific activity, 2 Ci/mmol; concentration, 1 mCi/ml).
Five days after the first topical application, all mice were administered with 250 μl of 83.50 μCi/ml HTdR (equal to 20.9 μCi HTdR) by intravenous injection via a tail vein.
3) Determination of incorporated HTDR
Approximately five hours after treatment with HTdR all mice were euthanized by intraperitoneal injection of VETANARCOL.
The draining lymph node cells were rapidly excised and pooled for each individual animal (2 nodes per mouse). Single cell suspensions (phosphate buffered saline) of pooled lymph node cells were prepared by gentle mechanical disaggregation through stainless steel gauze (200 μm mesh size). After washing two times with phosphate buffered saline (approx. 10 ml) the lymph node cells were resuspended in 5% trichloroacetic acid (approx. 3 ml) and incubated at approximately +4 ℃ for at least 18 hours for precipitation of precipitation of macromolecules. The precipitates were then resuspended in 5% trichloroacetic acid (1ml) and transferred to glass scintillation vials with 10 ml of 'Ultima Gold' scintillation liquid and thoroughly mixed.
The level of HTdR incorporation was then measured on a ß-scintillation counter. Similarly, background HTdR level were also measured in two 1ml-aliquots of 5% trichloroacetic acid. The ß-scintillation counter expresses HTdR incorporation as the number of radioactive disintegrations per minute (DPM). - Positive control substance(s):
- other: Alpha-Hexylcinnamaldehyde
- Statistics:
- The mean values and standard deviations of body weights and DPM/mouse value were calculated.
Results and discussion
- Positive control results:
- In this study STIMULATION INDICES of 2.5, 3.7 and 9.7 were determined with the test item at concentrations of 5%, 10% and 25% (w/v) in acetone:olive oil, 4:1 (v/v).
A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.).
The test item Alpha-Hexylcinnamaldehyde was found to be a sensitizer and an EC2 value of 7.08% (w/v) was derived.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: see Remark
- Remarks:
- For Control group, there is no S.I. (SD); For test group at concentrations of 5% (w/v) in ethanol:water, 7:3 (v/v), the S.I. (SD) is 1.0 (0.3); For test group at concentrations of 10% (w/v) in ethanol:water,7:3 (v/v), the S.I. (SD) is 1.3 (0.1); For test group at concentrations of 25% (w/v)in ethanol:water,7:3 (v/v), the S.I. (SD) is 1.4 (0.4).
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: see Remark
- Remarks:
- The level of HTdR incorporation was then measured on a ß-scintillation counter. Similarly, background HTdR levels were also measured in two 1ml-aliquots of 5% trichloroacetic acid. The ß-scintillation counter expresses HTdR incorporation as the number of radioactive disintegrations per minute(DPM). For Control group, the DPM is 681±180; For test group at concentrations of 5% (w/v) in ethanol:water, 7:3 (v/v), the DPM is 681±180; For test group at concentrations of 10% (w/v) in ethanol:water, 7:3 (v/v), the DPM: 894±87; For test group at concentrations of 25% (w/v) in ethanol:water, 7:3 (v/v), the DPM: 964±267.
Any other information on results incl. tables
Mortality: No deaths occurred during the study period.
Clinical signs: No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.
Body weights: Within the range commonly recorded for animals of this strain and age.
Group |
% (w/v) |
dpm/Mouse M±SD |
S.I. (SD) |
Statistical Analysis Dunnett-test (G=4, N=20, t=2.59) |
|
t Value |
Conclusion
|
||||
CG 1 |
--- |
681±180 |
-- |
-- |
-- |
TG 2 |
5 |
697±187 |
1.0 (0.3) |
0.13 |
--
|
TG 3 |
10 |
894±87 |
1.3 (0.1) |
1.77 |
--
|
TG 4 |
25 |
964±267 |
1.4 (0.4) |
2.35 |
--
|
--no significant different at p≤0.05 two sides
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- In this study stimulation indices of 1.0, 1.3 and 1.4 were determined with the test item at concentrations of 5%, 10% and 25% (w/v) in ethanol:water, 7:3 (v/v).
A test item is regarded as a sensitizer in the LLNA if the exposure to at least one concentration of the test item resulted in an incorporation of HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the STIMULATION INDEX (S.I.).
Based on these criteria, the test item was found to be a non-sensitizer when tested at up to the highest achievable concentration of 25% (w/v) in ethanol:water, 7:3 (v/v).
Dunnett-test
No signification difference of dpm/mouse was determined at up to the highest achievable concentration of 25% (w/v) comparing with the vehicle control group at p≤0.05 (two sides).
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