Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 227-030-9 | CAS number: 5610-94-6
- 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
OECD 429 (RL1): The test item is not sensitising to skin.
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:
- 14 Sep - 11 Oct 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted in 2010
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted in 2012
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Energie, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, protected from light
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: grinding of the test item in a mortar to reduce the particle size for increased skin contact
FORM AS APPLIED IN THE TEST
liquid (1 tablet disolved in 200 mL deionized water) - Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- Ola Hsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo RMS B.V., Inc, Horst, the Netherlands
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 - 12 weeks (pre-screen test), 11- 12 weeks (main study)
- Weight at study initiation: 20.9 - 21.8 g (pre-screen test), 19.3 - 20.3 g (main study) (range)
- Housing: 2 - 4 animals per cage, in Makrolon Type II (pre-screen test) / III (main study), with wire mesh top and granulated soft wood bedding
- Diet: 2018C Teklad Global 18% protein rodent diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: no
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): approx. 45 – 65
- Photoperiod (hrs dark / hrs light): 12 / 12 - Vehicle:
- propylene glycol
- Remarks:
- (PG)
- Concentration:
- 5, 10 and 20%
- No. of animals per dose:
- 2 females (pre-screen test)
4 females (main test) - Details on study design:
- PRE-SCREEN TESTS:
Two concentrations (10 and 20%, dissolved in PG) were applied topically to the ears of each animal (one mouse per concentration), once a day for 3 consecutive days. Animals were observed for clinical signs of systemic toxicity and local irritation at the application site at least once daily. Furthermore, body weights and ear thickness measurements were performed (body weight: before initial application and on Day 6, ear thickness: before initial application, on Day 6 and on Day 3). The ears were punched after sacrifice (Day 6) at the apical area using a biopsy punch (Ø 8 mm, corresponding to 0.5 cm2), pooled per animal and weighed using an analytical balance. None of the animals showed any signs of systemic toxicity or significant irritation (defined as an erythema score ≥ 3 and /or an increase of more than 25% in ear thickness). No mortality was observed.
Based on these results and considering that 20% was the maximum attainable concentration, 20 % (w/v) was selected as the highest test concentration for the main study. This concentration was expected not to induce systemic toxicity, nor to induce an increase in ear thickness exceeding 25% or to induce dermal erythema with a score of 3 or more.
- Compound solubility: 20% (maximum attainable concentration due to solubility properties)
- Irritation: no irritation was observed
- Systemic toxicity: no systemic toxicity was observed
- Ear thickness measurements: yes (less than 25% increase in ear thickness was measured)
- Erythema scores: 0 (both treatment groups)
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: 3H-methyl thymidine (3HTdR) incorporation, determined by ß-scintillation
- Criteria used to consider a positive response: SI ≥ 3
TREATMENT PREPARATION AND ADMINISTRATION:
25 μl of each dose formulation (5, 10 and 20%) or the vehicle alone were applied to the dorsal skin of each ear of each animal once a day for 3 consecutive days. On Day 6, 20 μCi 3H-methyl thymidine, contained in 250 μL of PBS (= 80.1 μCi/mL), was administered to each mouse via the tail vein. Approximately 5 h after administration, local lymph nodes were collected, pooled and separated by gentle mechanical disaggregation through a stainless steel gauze (200 μm mesh size). After washing two times in PBS the lymph node cells were treated with ~3 mL of 5% trichloroacetic acid (TCA) at ~4 °C for at least 18 h before the determination of the amount of 3H-methyl thymidine incorporation (as disintegrations per minutes (DPM)) on Day 7. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- All calculations conducted on the DPM values were performed with "R" (language and environment for statistical computing and graphics).
Mean values and standard deviations were calculated for the body weights. - Positive control results:
- The positive control substance (hexyl cinnamic aldehyde, 25% in AOO and 10% in AOO) induced positive and a negative reaction, respectively, determined by a DPM/lymph node of 8170.5 and 2908.9, respectively,compared with 1042.8 DPM/lymph node in the vehicle control group, leading to a SI of 7.84 and 2.79, respectively.
The EC3 value was calculated to be 10.6% (w/v) (using the results of 10 and 25% hexyl cinnamic aldehyde).
The historical control data range of the last 10 positive control experiments was 3.7 - 17.6 (= S.I. values) - Key result
- Parameter:
- SI
- Value:
- 0.82
- Test group / Remarks:
- 5% test group
- Key result
- Parameter:
- SI
- Value:
- 0.74
- Test group / Remarks:
- 10% test group
- Key result
- Parameter:
- SI
- Value:
- 0.54
- Test group / Remarks:
- 20% test group
- Key result
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- solvent control group (PG)
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA:
No significant lymphoproliferation (SI ≥ 3) was observed for the test item at treatment concentrations of 5, 10 and 20% (w/v) (see "Any other information on results" "Table 2").
DETAILS ON STIMULATION INDEX CALCULATION: SI = DPM/lymph node of a treated group divided by the DPM/lymph node of the respective solvent control group. Before DPM/lymph node values were determined, mean scintillation-background DPM (in main test = 17) was subtracted from test and control raw data. Since the lymph nodes of the animals of a dose group were pooled, DPM/ lymph node was determined by dividing the measured value by the number of pooled lymph nodes (= 8). The following values (DPM/lymph node) were obtained: 1084.8, 893.0, 804.6 and 585.5 in vehicle control (PG), 5, 10 and 20% test groups.
EC3 CALCULATION: Based on the obtained results no EC3 value of the test item could be calculated.
CLINICAL OBSERVATIONS:
No mortality or symptoms of systemic toxicity were observed in any treatment group. No signs of local skin irritation (indicated by an erythema score ≥ 3) or any other local effect were observed in any treatment group.
BODY WEIGHTS:
Body weights changes were within the range expected for animals of this strain and age. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item was not a skin sensitizer under the test conditions of the study.
- Executive summary:
The test item formulated in propylene glycol was assessed for its possible skin sensitizing potential according to OECD TG 429.
For this purpose a local lymph node assay was performed using test item concentrations of 5, 10, and 20%. The highest concentration tested was the highest concentration that could technically be achieved.
The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed.
In this study Stimulation Indices (S.I.) of 0.82, 0.74, and 0.54 were determined with the test item at concentrations of 5, 10, and 20% in PG, respectively.
The test item was not a skin sensitizer under the test conditions of the study.
Reference
Table 1: Results of the Pre-screen test
Body weights
Animal No. |
Concentration [%] |
Body weight (g) |
|||
Prior to 1st application |
Prior to Sacrifice (Day 6) |
Difference |
Difference [%] |
||
1 |
10 |
21.8 |
20.8 |
-1.0 |
-4.6 |
2 |
20 |
20.9 |
20.8 |
-0.1 |
-0.5 |
Ear thickness
Animal No. |
Concentration [%] |
Ear thickness |
||||||
Prior to 1st application [μm] |
Prior to 3rd application [μm] |
Prior to necropsy [μm] |
Difference Day 3 [µm] |
Ear swelling |
Difference Day 6 [μm] |
Ear swelling Day 6 [%] |
||
Mean (Right and Left Ear) |
||||||||
1 |
10 |
237.5 |
245.0 |
230.0 |
7.5 |
3.2 |
-7.5 |
-3.2 |
2 |
20 |
245.0 |
255.0 |
247.5 |
10.0 |
4.1 |
2.5 |
1.0 |
Ear Weights
Animal No. |
Concentration [%] |
Ear weights after necropsy (mg per animal) |
% Increase compared to vehicle values |
1 |
10 |
25.77 |
1.5 |
2 |
20 |
26.52 |
4.4 |
Mean of historical vehicle controls (propylene glycol): 25.4 mg/animal
Ear Erythema
Animal No. |
Score |
|||||||
within 1 h after 1. appl. |
24 h 1. appl. |
within 1 h after 2. appl. |
24 h 2. appl. |
within 1 h after 3. appl. |
24 h 3. appl. |
Day 5 |
Day 6 |
|
1 |
0* |
0 |
0* |
0 |
0* |
0 |
0 |
0 |
2 |
0* |
0 |
0* |
0 |
0* |
0 |
0 |
0 |
Score:
0 = No visible erythema
1 = Very slight erythema
2 = Well defined erythema
3 = Moderate to severe erythema
4 = Severe erythema to formation of eschar which prevents grading of erythema
*substance residuals
Table 2: Stimulation index in mice (main test)
Compound |
Concentration [%] |
DPM/ lymph node |
Stimulation index |
Judgement |
PG |
100 |
1084.8 |
1.00 |
- |
Test item |
5 |
893.0 |
0.82 |
Negative |
10 |
804.6 |
0.74 |
||
20 |
585.5 |
0.54 |
||
AOO* |
100 |
1042.8 |
1.00 |
- |
HCA* |
10 |
2908.9 |
2.79 |
Negative |
25 |
8170.5 |
7.84 |
Positive |
AOO = Acetone : olive oil (4:1 (v/v) mixture)
HCA = Hexyl cinnamic aldehyde
PG = Polyethylene glycol
- = Not applicable
* = Performed in separate experiment
Table 3: Body weight (main test)
Compound |
Concentration [%] |
Animal ID No. |
Body weight |
|
Day 1 [g] |
Day 6 [g] |
|||
PG |
100 |
1 |
19.3 |
20.2 |
2 |
20.3 |
21.1 |
||
3 |
19.7 |
19.4 |
||
4 |
20 |
20.7 |
||
Mean ± SD |
19.8 ± 0.4 |
20.4 ± 0.7 |
||
Test item |
5 |
5 |
20 |
20.4 |
6 |
18.3 |
19.9 |
||
7 |
21.7 |
22.2 |
||
8 |
22.3 |
21.4 |
||
Mean ± SD |
20.6 ± 1.8 |
21.0 ± 1.0 |
||
10 |
9 |
18.3 |
19.3 |
|
10 |
20 |
20.3 |
||
11 |
19.9 |
20.4 |
||
12 |
20.6 |
21 |
||
Mean ± SD |
19.7 ± 1.0 |
20.3 ± 0.7 |
||
20 |
13 |
21.1 |
20.4 |
|
14 |
19.5 |
18.8 |
||
15 |
20.4 |
20.7 |
||
16 |
21.4 |
22.9 |
||
Mean ± SD |
20.6 ± 0.8 |
20.7 ± 1.7 |
AOO = Acetone : olive oil (4:1 (v/v) mixture)
HCA = Hexyl cinnamic aldehyde
PG = Polyethylene glycol
SD = Standard deviation
Historical Positive Control values (Feb 2012 - Apr 2016)
Hexyl cinnamic aldehyde (25% in an acetone : olive oil 4:1 (v/v) mixture): SI range = 3.7 - 17.6
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the data, the test item is not classified for skin sensitisation according to Regulation (EC) No 1272/2008.
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.