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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
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2010-01-19 to 2010-04-16
- Reliability:
- 1 (reliable without restriction)
- 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 (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Breeder Janvier
- Age at study initiation: 9 weeks
- Weight at study initiation: 20.4 ± 1.1 g
- Housing: individual, crystal polystyrene cages
- Diet (e.g. ad libitum): "SSNIFF R/M-H pelleted maintenance diet", ad lib
- Water (e.g. ad libitum): drinking water filtered using a 0.22 micron meter filter, ad lib
- Acclimation period: 5 days at least
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 4 March 2009 To: 02 April 2009 - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 25, 10, 5, 2.5, 1 and 0 % (v/v)
- No. of animals per dose:
- 4 (at all doses)
- Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: appropriate solution in AOO vehicle
- Irritation: a range-finding test performed on mice at the concentrations of 10, 25, 50 and 100%
MAIN STUDIES
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: SI ≥ 3
TREATMENT PREPARATION AND ADMINISTRATION:
in the vehicle, at 25 µL on both ears - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Positive control results:
- The positive control results were valid: the conditions of the test allow the identification of positive dermal sensitisers.
- Parameter:
- SI
- Remarks on result:
- other: see Table 1
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: see Table 1
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information See in Attached background material "Statement CAE JFN 24th July 2011.pdf" Criteria used for interpretation of results: expert judgment
- Conclusions:
- Preliminary experiments showed that CAE concentrations > 25% induced a skin irritation at day 6. Thus, the 25% concentration was retained for highest tested concentration for the LLNA. Conclusion was that CAE should be considered as a weak sensitizer since the EC3 value was equal to 12%.
Of note, the 25% CAE concentration was not totally devoid of irritant properties as reported by study director:
i) clinical observation showed dryness of the 25% C CAE-treated ears in all animals (4/4) and erythema in ¼ animals (page 7 and 20/33);
ii) a 20 to 30% ear thickness increase was noted at day 6 in all 25% CAE-treated animals (page 17/33-preliminary exp. and page 22/33 pivotal exp.). Therefore, we interpret the results of the LLNA as false positives because of the use of a “border-line” irritant concentration of CAE.
If the LLNA had been conducted with the non-irritant 10% concentration, it would have been negative. - Executive summary:
According to the study director, the test item should be considered as a weak sensitizer based on the EC3 of 12%.
According to the expert judgment, there are 4 types of arguments for not taking into account the positive CAE LLNA:
i) LLNA is not validated for UVCB;
ii) positive LLNA is not synonymous of skin sensitization properties;
iii) there are strong arguments to consider the positive LLNA as false-positive through an irritant effect of CAE and the vehicle;
iv) there is no bibliographic and epidemiological data on CAE-induced allergy.
Please see the document "Statement CAE JFN 24th July 2011.pdf" for more details.
Based on these arguments, CAE is non-classified as skin sensitiser.
Reference
Table 1:
Concentration (% v/v in vehicle) |
dpm per node | SI | Increase in ear thickness (% between day 1 and day 6) | Interpretation of irritancy |
Vehicle AOO | 45.83 | - | 3.13 | - |
Test item 1% | 45.06 | 0.98 | 4.04 | Non irritant |
Test item 2.5% | 42.75 | 0.93 | 6.38 | Non irritant |
Test item 5% | 36.00 | 0.79 | 4.12 | Non irritant |
Test item 10% | 74.26 | 1.62 | 9.38 | Non irritant |
Test item 25% | 475.96 | 10.39 | 20.41 | Slightly irritant |
HCA 25% | 317.92 | - | - | - |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Weight of evidence determination using expert judgment:
There are 4 types of arguments for not taking into account the positive CAE LLNAs:
i) LLNA is not validated for UVCB;
ii) positive LLNA is not synonymous of skin sensitization properties;
iii) there are strong arguments to consider the positive LLNA as false-positive through an irritant effect of CAE and the vehicle;
iv) there is no bibliographic and epidemiological data on CAE-induced allergy.
Please see attached document below for the Assessment of contact hypersensitivity to CAE in the mouse Local Lymph Node Assay signed by Professor NICOLAS: "Statement CAE JFN July 24th 2011.pdf"
Migrated from Short description of key information:
Skin sensitisation.001: According to the study director, the test item should be classified as a skin sensitizer based on the EC1.4 of 10% v/v. Significant irritancy was observed from 50% v/v only.
Skin sensitisation.002: According to the study director, the test item should be considered as a weak sensitizer based on the EC3 of 12%.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
According to Article 9.3 then specifies that "where the criteria cannot be applied directly to available identified information, manufacturer, importers and downstream users shall carry out an evaluation by applying a weight of evidence determination using expert judgment in accordance with section 1.1.1 of Annex 1 to this Regulation weighing all available information having a bearing on the determination of the hazards of the substance of the mixture in accordance with section 1.2 of Annex XI to Regulation (EC) N°1907/2006.
CLP classification Criteria related to skin sensitization Paragraph 3.4.2.2 of Annex 1 of the CLP provides the rules applicable to the evaluation of information for the determination of the classification of skin sensitizers. Essentially, it provides that a substance shall be classified as skin sensitizer (Category 1) in accordance with the following criteria:
·If there evidence in humans that the substance can lead to sensitization by skin contact in a substantial number of persons, or
·If there are positive results from an appropriate animal test.
As the false positive LLNAs results cannot be taken into account for classification purpose and there is no evidence of skin sensitization in humans.
There is no definitive argument to consider CAE as a skin sensitizer. LLNA is not validated for UVCB. Most of the data obtained with CAE in the LLNA and in the ocular and skin tolerance assays show that CAE is a mild irritant. Furthermore, no human relevant cases of sensitization have been reported.
Therefore, the positive LLNA can be attributed to the irritant properties of CAE yielding to false positive LLNA.
Consequently, CAE is non-classified as skin sensitiser.
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