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EC number: 208-654-0 | CAS number: 537-00-8
- 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
Under the conditions of the study, the test material is not considered to be a skin sensitiser.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 December 2015 and 05 January 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The rare earth substances are known to give false positives in the LLNA studies. The Maximisation study was therefore deemed to be more appropriate for investigating the skin sensitisation potential of this substance.
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Batch No.of test material: CEACK1/16
- Expiration date of the lot/batch: 17 October 2018
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, darkness
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: freshly prepared in olive oil for the intradermal injections and in liquid paraffin for the topical applications. - Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 3 to 4 weeks old
- Weight at study initiation: 297 to 362 g
- Housing: in groups up to 3 in polycarbonate containers, the floor of which was covered with dust-free cuttings and the top fitted with a stainless steel lid.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Air changes: At least ten per hour
- Photoperiod: twelve hours continuous light (07.00 to 19.00) and twelve hours darkness. - Route:
- other: intradermal and topical
- Vehicle:
- other: Olive oil (intradermal), liquid paraffin (topical)
- Concentration / amount:
- 5 % / 0.1 mL (intradermal)
40 % / 0.5 mL (topical) - Day(s)/duration:
- Intradermal induction took place on Day 0. On Day 8, animals received a topical induction application which was covered for 48 hours.
- Adequacy of induction:
- other: Non-irritant substance but skin pre-treated with SLS prior to topical induction
- No.:
- #1
- Route:
- other: topical
- Vehicle:
- other: liquid paraffin
- Concentration / amount:
- 40 and 20 % / 1 sample cup
- Day(s)/duration:
- On day 21 for 24 hour exposure
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- Control group: 5 animals
Treatment group: 10 animals - Details on study design:
- RANGE FINDING TESTS:
- DETERMINATION BY INTRADERMAL INJECTION OF THE MAXIMAL NON NECROTISING CONCENTRATION (MNNC)
This test was conducted for the purpose of defining a MNNC of the test material which, on intradermal injection during the induction phase, does not risk causing too great a lesion (non-necrotising concentration), should be well-tolerated systemically and should be the highest to cause mild-to-moderate skin irritation. Two animals received a volume of 0.1 mL of the test material, on both sides of the spine, at 4 concentrations: diluted at 5, 2, 1 and 0.5 % in olive oil in view to determine the MNNC. A macroscopic evaluation of the cutaneous reactions was conducted 24 hours after the injections.
- DETERMINATION BY TOPICAL APPLICATION OF THE PRE-MAXIMAL NON-IRRITANT CONCENTRATION (PRE-MNIC)
This test, which allowed evaluating the irritancy potential of the test material, defined whether an application of sodium lauryl sulfate would be needed during topical induction phase.The test material was applied on the dorso-lumbar zone of two guinea pigs shorn beforehand, with occlusive dressing for 24 hours, at 4 different concentrations: diluted at 40, 30, 20 and 10 % in liquid paraffin. After the removal of the occlusive dressing, the treated areas were rinsed with liquid paraffin. A macroscopic evaluation of the cutaneous reactions was conducted 24 hours after removal of the dressing.
- DETERMINATION BY TOPICAL APPLICATION OF THE MAXIMAL NON IRRITANT CONCENTRATION (MNIC)
This test was carried out for the purpose of determining the MNIC of the test material without risk of an irritant effect during the challenge phase. Three guinea pigs were treated according to the same treatment as animals from GROUP 1 (control) for the induction phase (i.e. olive oil and liquid paraffin). During the challenge phase, the animals were treated with the test material placed onto the selected treatment sites and covered with an occlusive dressing for a period of 24 hours at 4 different concentrations: diluted at 40, 30, 20 and 10 % in liquid paraffin. A macroscopic evaluation of the cutaneous reactions was conducted 24 and 48 hours after removal of the occlusive dressing.
MAIN STUDY
A. INDUCTION EXPOSURE
- Intradermal Induction: (Day 0) After shearing the scapular zone, three pairs of intradermal injections (ID) of 0.1 mL were performed on the scapular zone in such a way as an injection on each pair is placed to either side of the spine as follows:
Group 1 (control):
2 ID: Freund’s Complete Adjuvant diluted at 50 % in olive oil,
2 ID: olive oil,
2 ID: a mixture with equal volumes v/v (Freund’s Complete Adjuvant at 50% and olive oil)
Group 2 (Treated):
2 ID: Freund’s Complete Adjuvant diluted at 50 % in olive oil,
2 ID: test material at 5% in olive oil,
2 ID: a test mixture in equal volumes v/v (Freund’s Complete Adjuvant at 50% and the test material at 10% in olive oil)
- Topical Induction: On day 7 the scapular zone of all the animals in each group, shorn beforehand, was brushed with a solution of sodium lauryl sulfate at 10% in thick vaseline, in order to create a local irritation. On day 8 a topical application under occlusive dressing (25 mm x 25 mm non-woven swab of 4-layer patch held in contact with the skin by means of 50 mm wide hypoallergenic adhesive tape) for 48 hours was performed on the injection sites of each animal.
Group 1 (control) recieved 0.5 mL of liquid paraffin
Group 2 (treated) recieved 0.5 mL of the test material at 40% in liquid paraffin.
On day 10 the occlusive dressing was removed and the treated areas were rinsed with liquid paraffin.
- Rest phase
The animals of both groups were left for 10 days.
B. CHALLENGE EXPOSURE
On day 21 the experimental procedure of this phase was identical for both group 1 (Control) and group 2 (Treated) submitted to this experimentation: on the previously shorn dorso-lumbar zone, an application, under occlusive dressing, was performed during 24 hours:
1 sample cup containing the test material diluted at 40% in liquid paraffin (MNIC) and 1 sample cup containing the test material diluted at 20% in liquid paraffin (1/2 MNIC).
The occlusive dressing was removed on day 22 and the treated areas were rinsed with liquid paraffin.
The first reading was taken on day 23, 24 hours after the patch removal and the second reading was on day 24, 48 hours after the patch removal.
INTERPRETATION OF RESULTS
The test material will be regarded as a sensitiser if 30% or more of the test animals show a sensitisation response:
Sub-category 1A:
≥ 30% responding at ≤ 0.1% intradermal induction dose or
≥ 60% responding at > 0.1% to ≤ 1% intradermal induction dose
Sub-category 1B:
≥ 30% to < 60% responding at > 0.1% to ≤ 1% intradermal induction dose or
≥ 30% responding at > 1% intradermal induction dose - Positive control substance(s):
- yes
- Remarks:
- α-hexylcinnamaldehyde
- Positive control results:
- Under these experimental conditions, the reference substance α-Hexylcinnamaldehyde must be classified in category 1 “Skin sensitisation” sub-category 1B. The signal word “Warning” and hazard statement H317 “May cause an allergic skin reaction” are required.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 20 / 40 %
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 20 / 40 %
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 20 / 40 %
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 20 / 40 %
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Interpretation of results:
- other: Not sensitising in accordance with EU criteria
- Conclusions:
- Under the conditions of the study, the test material is not considered to be a skin sensitiser.
- Executive summary:
The skin sensitisation potential of the test material was determined in accordance with the standardised guidelines OECD 406 and EU Method B.6, using the guinea pig maximisation test under GLP conditions.
According the results of the pre-tests, the test material was applied to 10 Guinea pigs during the induction phase (intradermic injection at 5% and topical application at 40%). Induction was followed with a 10-day rest phase. During the challenge phase, animals received a topical application of test material (at 40% and at 20% in liquid paraffin) under an occlusive dressing for a period of 24 hours.
In the treated group (treatment dose of 40%), no macroscopic cutaneous reactions attributable to allergy were noted after the challenge phase. In the control group (associated with the treatment dose of 40%), no macroscopic cutaneous intolerance reactions were recorded after the challenge phase.
In the treated group (treatment dose of 20%), no macroscopic cutaneous reactions attributable to allergy were noted after the challenge phase. In the control group (associated with the treatment dose of 20%), no macroscopic cutaneous intolerance reactions were recorded after the challenge phase.
The positive control met the acceptability criteria so the study was considered to be valid.
Under the conditions of this the study, the test material is not considered to be a skin sensitiser.
Reference
PRELIMINARY STUDIES
- MNNC Determination
24 hours after the injections, moderate erythema was observed in the animals at the tested concentration of 5%. No cutaneous reaction was noted in the animals at the tested concentrations of 2, 1 and 0.5%. The first induction of the Group 2 has been carried out by intradermal injection at the maximal non necrosing concentration of 5%.
- Pre- MNIC Determination
24 hours after the removal of the occlusive dressings, no cutaneous reaction was noted whatever the tested concentration. In view of these results, the concentration selected was 40% for the 2nd induction of the Group 2 and the MNIC determination began at the concentration of 40%.
- MNIC Determination
24 and 48 hours after the removal of the occlusive dressings, no cutaneous reaction was noted whatever the tested concentration. In view of this result, the concentrations selected were 40% (MNIC) and 20% (1/2 MNIC).
MAIN STUDY
- Induction phase Group 2: Moderate erythema was noted in three animals (3/10), discrete erythema was noted in four animals (4/10) and no cutaneous reaction was noted in the other three animals (3/10) 24 hours after the first induction. Dryness of the skin was noted in all animals (10/10) after the second induction.
- Induction phase Group 1: No cutaneous reaction was noted 24 hours after the first induction. After the second induction, dryness of the skin was noted in all animals (5/5).
- Challenge phase Groups 1 & 2: In the treated group (treatment dose of 40%), no macroscopic cutaneous reactions attributable to allergy were noted after the challenge phase. In the control group (associated with the treatment dose of 40%), no macroscopic cutaneous intolerance reactions were recorded after the challenge phase. In the treated group (treatment dose of 20%), no macroscopic cutaneous reactions attributable to allergy were noted after the challenge phase. In the control group (associated with the treatment dose of 20%), no macroscopic cutaneous intolerance reactions were recorded after the challenge phase. Results of the challenge are summarised in Table 1.
Table 1: Macroscopic evaluation (readings at 24 and 48 hours) of cutaneous reactions
Groups |
Reading time (hrs) |
Concentrations (%) |
Incidence |
% of positive responses ≥1 |
% of animal sensitised |
|||
0 |
1 |
2 |
3 |
|||||
Group 1: control |
24 |
40 |
5 |
0 |
0 |
0 |
0 |
- |
48 |
40 |
5 |
0 |
0 |
0 |
0 |
- |
|
24 |
20 |
5 |
0 |
0 |
0 |
0 |
- |
|
48 |
20 |
5 |
0 |
0 |
0 |
0 |
- |
|
Group 2: treated |
24 |
40 |
10 |
0 |
0 |
0 |
0 |
0 |
48 |
40 |
10 |
0 |
0 |
0 |
0 |
0 |
|
24 |
20 |
10 |
0 |
0 |
0 |
0 |
0 |
|
48 |
20 |
10 |
0 |
0 |
0 |
0 |
0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
The skin sensitisation potential of the test material was determined in accordance with the standardised guidelines OECD 406 and EU Method B.6, using the guinea pig maximisation test under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).
According the results of the pre-tests, the test material was applied to 10 Guinea pigs during the induction phase (intradermic injection at 5% and topical application at 40%). Induction was followedwith a 10-day rest phase. During the challenge phase, animals received a topical application of test material (at 40% and at 20% in liquid paraffin) under an occlusive dressing for a period of 24 hours.
In the treated group (treatment dose of 40%), no macroscopic cutaneous reactions attributable to allergy were noted after the challenge phase.In the control group (associated with the treatment dose of 40%), nomacroscopiccutaneous intolerance reactions were recorded after the challenge phase.
In the treated group (treatment dose of 20%), no macroscopic cutaneous reactions attributable to allergy were noted after the challenge phase.In the control group (associated with the treatment dose of 20%), nomacroscopiccutaneous intolerance reactions were recorded after the challenge phase.
The positive control met the acceptability criteria so the study was considered to be valid.
Under the conditions of this the study, the test material is not considered to be a skin sensitiser.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin sensitisation.
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