Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 242-745-6 | CAS number: 19009-56-4
- 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

Endpoint summary
Administrative data
Description of key information
Skin Sensitisation: Skin sensitiser (category 1B); OECD 429, Anon, 2009
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:
- 15 Jun - 14 Jul 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Study conducted in accordance with international guidelines and in accordance with GLP. All guideline criteria were met.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- GLP compliance:
- yes
- Remarks:
- Exceptions to GLP noted, but satsifactory counterpoints are provided to ensure that the study can still be considered GLP compliant
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Jackson Laboratories, Bar Harbor, ME, USA, 04069
- Females (if applicable) nulliparous and non-pregnant: not specified (but were purpose bred and experimentally naive)
- Microbiological status of animals, when known: N/A
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 18-25g
- Housing: Group housed 5 per cage
- Diet (e.g. ad libitum): Ad libitum: Harlan Teklad Certified Rodent Chow 7012c
- Water (e.g. ad libitum): Ad libitum: tap water
- Acclimation period: Acclimated to housing 5 days prior to first day of dosing
- Indication of any skin lesions: All animals assessed for general health and only those deemed suitable were used in the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C
- Humidity (%): Relative humidity: 44-62%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 light/12 dark hrs
- IN-LIFE DATES: From: To: 8 July 2009 - 14 July 2009 - Vehicle:
- other: EtOH/DEP
- Concentration:
- The test article was prepared at 2.5%, 5%, 10%, 25% or 50% v/v.
The positive control was prepared daily as 5%, 15% and 35% solutions in the vehicle.
Justification for dose levels: generally, doses were selected so that the highest concentration maximised exposure whilst avoiding systemic toxicity and excessive local irritation. Doses were selected based on known reported uses of the material. - No. of animals per dose:
- n=45
No. of test groups=9
No. of animals per dose (including control): 5 - Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility:
- Irritation: animals were examined at least once daily for abnormalities and general health
- Systemic toxicity: N/A
- Ear thickness measurements: N/A
- Erythema scores: N/A
MAIN STUDY
-Route: Topically on the dorsal surface of both ears
Frequency: Once daily for 3 consecutive days (Days 1-3). The timing of dose administration remained consistent (±2 hours) during the dosing phase.
Procedure: A volume of 25ul/ear was applied using a micro pipette.
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
- Criteria used to consider a positive response: N/A
TREATMENT PREPARATION AND ADMINISTRATION: The test substance was applied topically - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- SYSTAT v 9.01 developed by SPSS, Inc.
Individual DPM values were analyzed and the mean DPM plus the standard error were calculated for each group. Body weights on days 1 and 6 and body weight changes were evaluated. The evaluation of the equality of means for body weight data was made by a one-way analysis of variance using the F distribution to assess statistical distribution. If statistically significant differences between the means are found, a Dunnett's test was used to determine the degree of significance from the control means.
Inidivdiual DPM values were analysed by log transformation (base 10) of the data. The evaluation of the equality of means for the DPM and body weight data was made by a one-way analysis of variance using the F distribution to assess statistical significance. - Positive control results:
- Clinical observations:
The positive control α- Hexylcinnamaldehyde (HCA) caused no mortality. Ears appeared wet in all treated animals Days 2-4. Ears appeared wet at 35% dose on Day 5.
LLNA results:
At termination, animals treated with 35% HCA exhibited enlarged lymph nodes. Exposure to HCA at 5%, 15% and 35% v/v resulted in stimulation indices of 1.2, 1.9 and 9.4 respectively. A 3-fold or greater increase in proliferative activity to the concurrent vehicle control is considered a positive response. - Key result
- Parameter:
- EC3
- Value:
- 23.6
- Parameter:
- SI
- Value:
- 0.9
- Test group / Remarks:
- 2.5 %
- Parameter:
- SI
- Value:
- 1.1
- Test group / Remarks:
- 5 %
- Parameter:
- SI
- Value:
- 1.1
- Test group / Remarks:
- 10 %
- Parameter:
- SI
- Value:
- 3.2
- Test group / Remarks:
- 25 %
- Parameter:
- SI
- Value:
- 12.4
- Test group / Remarks:
- 50 %
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- The test substance is considered to have skin sensitising activity if, at one or more concentrations it induces a 3-fold or greater increase in proliferative activity relative to the concurrent vehicle treated control. Thus, a stimulation index of =>3.0 is regarded as a positive response. Treatment with LLNA-641 at concentrations of 25% and 50% v/v resulted in stimulation indices stimulation indices of 3 or greater and hence is considered to have skin sensitising activity. The EC3 was calculated to be 23.6% (Category 1B - moderate potency).
- Executive summary:
The test substance was assessed for skin sensitisation according to OECD Testing Guidelines 429 and OPPTS Guidelines 870.2600.
The test article was prepared at 2.5%, 5%, 10%, 25% or 50% v/v. The positive control was prepared daily as 5%, 15% and 35% solutions in the test vehicle. 7 groups of 5 female CBA/J mice were treated on the dorsal surface of both ears once per day for 3 days. On Day 6, the mice were euthanised and the lymph nodes removed. There was no mortality during the experiment, and there was no erythema or edema. Ears appeared wet in the mice treated at doses 25% and 50% on Days 2 and 4. Ears appeared wet in mice treated with the 50% dose level on Day 5. The mean body weights and body weight changes of mice treated with LLNA-641 on days 1 and 6 showed no statistically significant differences. Therefore, administration of the test item appeared not to exert overt toxicity.
As per the CLP criteria, the calculated EC3 (23.6%) is greater than 2%, which designates the substance as skin sensiser category 1B.
Reference
Table 1 demonstrates the dermal irritation scores attributed to each test animal. The Draize (1959) definition for scoring dermal irritation was used. Each dosed test animal yielded a dermal irritation score of 0 (i.e no erythema and no edema) an all tested days. Table 2 shows the Local Lymph Node Assay results. Table 3 is a breakdown of individual animal data.
There was no mortality in all test animals.
Clinical observations:
No erythema or edema was noted in any of the mice at 2.5%, 5%, 10%, 25% or 50% dose levels. Ears appeared wet in the mice treated at doses 25% and 50% on Days 2 and 4. Ears appeared wet in mice treated with the 50% dose level on Day 5. The mean body weights and body weight changes of mice treated with LLNA-641 on Days 1 and 6 showed no statistically significant differences. Therefore, administration of the test item appeared not to exert overt toxicity.
LLNA results:
At termination, lymph nodes from the mice treated with 2.5%, 5%, 10% or 25% were normal in size and appearance. Exposure to LLNA-641 resulted in stimulation indices 0.9, 1.1, 1.1, 3.2 and 12.4 respectively. In addition, the responses with 25% and 50% of the test article was statistically significant (p<0.001) when the log DPM was compared to the vehicle group. Since the data indicated a positive response the EC3 was calculated (see below equation) and determined to be 23.6%.
EC3 = c+[(3-d)/(b-d)](a-c)
where the data points lying immediately above and below the SI value of 3 have the co-ordinates (a,b) and (c,d) respectively.
Exposure to HCA at 5%, 15% and 35% (v/v) resulted in stimulation indices of 1.2, 1.9 and 9.4, respectively. A 3-fold or greater increase in proliferative activity relative to the concurrent vehicle control is considered a positive response.
2.5%, 5%, 10% or 25%
Table 1 Dermal irritation scores
MOUSE NO. |
GROUP |
DAY 1 |
DAY 2 |
DAY 3 |
DAY 4 |
DAY 5 |
DAY 6 |
||||||
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
||
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
4 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
5 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
6 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
7 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
8 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
9 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
10 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
11 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
12 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
13 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
14 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
15 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
16 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
17 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
18 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
19 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
20 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
21 |
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22 |
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23 |
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
24 |
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
25 |
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
26 |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
27 |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
28 |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
29 |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
30 |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
31 |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
32 |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
33 |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
34 |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
35 |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 = no (erythema/edema)
Table 2. Local Lymph Node Assay
GROUP |
TREATMENT |
DOSE |
DPM |
SI(Test/control Ratio) |
RESULTS* |
1 |
DEP/EtOH |
- |
320.7±49.7 |
- |
- |
2 |
LLNA-641 |
2.5% |
295.2±41.3 |
0.9 |
- |
3 |
LLNA-641 |
5% |
358.4±64.8 |
1.1 |
- |
4 |
LLNA-641 |
10% |
351.2±57.4 |
1.1 |
- |
5 |
LLNA-641 |
25% |
1035.5±138.7** |
3.2 |
+ |
6 |
LLNA-641 |
50% |
3968.6±855.3** |
12.4 |
+ |
7 |
HCA |
5% |
38.4±114.5 |
1.2 |
- |
8 |
HCA |
15% |
602.4±117.2 |
1.9 |
- |
9 |
HCA |
35% |
3027.4±208.9** |
9.4 |
+ |
*test/control ratio of 3.0 or greater represents a positive result
**Statistically significant difference when log DPM compared to the vehicle control group (Group 1) (p<0.001)
Table 3. individual animal data
GROUP |
ANIMAL # |
DPM |
LogDPM |
BODY WEIGHT ON DAY 1 |
BODY WEIGHT ON DAY 6 |
CHANGE IN BODY WEIGHT |
DEP/EtOH |
1 |
258.81 |
2.41 |
25 |
26 |
1 |
2 |
322.08 |
2.51 |
25 |
26 |
1 |
|
3 |
169.15 |
2.23 |
21 |
21 |
0 |
|
4 |
428.58 |
2.63 |
20 |
20 |
0 |
|
5 |
425.04 |
2.63 |
22 |
23 |
1 |
|
LLNA-641 2.5% |
6 |
182.98 |
2.26 |
22 |
22 |
0 |
7 |
397.12 |
2.60 |
24 |
24 |
0 |
|
8 |
214.63 |
2.33 |
24 |
24 |
0 |
|
9 |
356.49 |
2.55 |
23 |
25 |
2 |
|
10 |
325.00 |
2.51 |
25 |
28 |
3 |
|
LLNA-641 5% |
11 |
317.04 |
2.50 |
22 |
22 |
0 |
12 |
529.33 |
2.72 |
21 |
21 |
0 |
|
13 |
323.94 |
2.51 |
21 |
20 |
-1 |
|
14 |
465.03 |
2.67 |
24 |
24 |
0 |
|
15 |
156.88 |
2.20 |
20 |
20 |
0 |
|
LLNA-641 10% |
16 |
278.46 |
2.44 |
20 |
25 |
5 |
17 |
570.42 |
2.76 |
19 |
20 |
1 |
|
18 |
289.84 |
2.46 |
25 |
19 |
-6 |
|
19 |
257.53 |
2.41 |
21 |
22 |
1 |
|
20 |
359.55 |
2.56 |
19 |
19 |
0 |
|
LLNA-641 25% |
21 |
1305.62 |
3.12 |
23 |
22 |
-1 |
22 |
552.08 |
2.74 |
22 |
21 |
-1 |
|
23 |
901.68 |
2.96 |
24 |
23 |
-1 |
|
24 |
1200.52 |
3.08 |
22 |
21 |
-1 |
|
25 |
1217.46 |
3.09 |
24 |
22 |
-2 |
|
LLNA-641 50% |
26 |
2471.75 |
3.39 |
25 |
25 |
0 |
27 |
2404.76 |
3.38 |
23 |
23 |
0 |
|
28 |
4991.02 |
3.70 |
21 |
21 |
0 |
|
29 |
6834.54 |
3.83 |
22 |
23 |
1 |
|
30 |
3141.11 |
3.50 |
23 |
23 |
0 |
|
HCA 5% |
31 |
149.61 |
2.17 |
23 |
24 |
1 |
32 |
150.88 |
2.18 |
20 |
21 |
1 |
|
33 |
744.57 |
2.87 |
23 |
22 |
-1 |
|
34 |
526.26 |
2.72 |
24 |
24 |
0 |
|
|
35 |
330.77 |
2.52 |
24 |
25 |
1 |
HCA 15% |
36 |
910.43 |
2.96 |
21 |
21 |
0 |
37 |
688.52 |
2.84 |
21 |
22 |
1 |
|
38 |
219.47 |
2.34 |
18 |
18 |
0 |
|
39 |
483.83 |
2.68 |
22 |
23 |
1 |
|
40 |
709.75 |
2.85 |
20 |
21 |
1 |
|
HCA 35% |
41 |
3046.45 |
3.48 |
19 |
19 |
0 |
42 |
3038.42 |
3.48 |
22 |
21 |
-1 |
|
43 |
3650.50 |
3.56 |
20 |
20 |
0 |
|
44 |
3068.61 |
3.49 |
22 |
22 |
0 |
|
45 |
2332.87 |
3.37 |
23 |
22 |
-1 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
The test substance was assessed for skin sensitisation according to OECD Testing Guidelines 429 and OPPTS Guidelines 870.2600.
The test article was prepared at 2.5%, 5%, 10%, 25% or 50% v/v. The positive control was prepared daily as 5%, 15% and 35% solutions in the test vehicle. 7 groups of 5 female CBA/J mice were treated on the dorsal surface of both ears once per day for 3 days. On Day 6, the mice were euthanised and the lymph nodes removed. There was no mortality during the experiment, and there was no erythema or edema. Ears appeared wet in the mice treated at doses 25% and 50% on Days 2 and 4. Ears appeared wet in mice treated with the 50% dose level on Day 5. The mean body weights and body weight changes of mice treated with LLNA-641 on days 1 and 6 showed no statistically significant differences. Therefore, administration of the test item appeared not to exert overt toxicity.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The criteria are met for classification of the substance as a skin sensitiser (skin sens. 1B) in accordance with Regulation (EC) No 1272/2008 (CLP).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
