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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 613-145-5 | CAS number: 63139-21-9
- 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
In an in vivo Local Lymph Node Assay (LLNA) according to OECD guideline 429, the test item was not found to be a skin sensitiser under the described conditions (reference 7.4.1-1).
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:
- 2007-07-02 to 2007-09-26
- 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:
- 2002-04-24
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Netherlands B.V., Postbus 6174
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 7 - 8 weeks (beginning of acclimatisation)
- Weight at study initiation: 17.9 - 23 g
- Housing: single, Makrolon Type I cages, with wire mesh top and granulated soft wood bedding
- Diet: Ad libitum
- Water: Ad libitum
- Indication of any skin lesions: Only animals without any visible signs of illness were used for the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 3°C
- Humidity (%): 30-85
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- dimethylformamide
- Concentration:
- 5, 10, and 25% (w/v) of the test item in dimethyl formamide;
25% = highest test item concentration, which could be technically used - No. of animals per dose:
- 5 females/dose
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: The highest test item concentration, which could be technically used was a 25 % solution in dimethyl formamide
- Irritation: To determine the highest non-irritant test concentration or the highest technically applicable concentration, a pretest was performed in two mice on three consecutive days. At concentrations of 2.5, 5, 10, and 25%, the treated mice did not show any signs of irritation.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay (LLNA)
- Criteria used to consider a positive response:
1) The exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
2) 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 balance and the vehicle was quantitatively added. The test item concentrations were prepared serially. Homogeneity of the test item in the vehicle was maintained during treatment with the magnetic stirrer.
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 dimethyl formamide. The application volume, 25 µL, was spread over the entire dorsal surface (0 ~ 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).
3HTdR (specific activity, 2 Ci/mmol; concentration, 1 mCi/mL) was administered five days after the first topical application. All mice were administered with 250 µL of 79.9 µCi/mL^3 HTdR (corresponds to 20.0 µCi 3HTdR per mouse) by intravenous injection via a tail vein. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The ANOVA (Dunnett-test) was conducted to assess whether the difference between test item groups and negative control (vehicle) group is statistically significant. Statistical significance was at the five per cent level (p < 0.05). However, both biological and statistical significance were considered together.
- Positive control results:
- The validation- / positive control experiment was performed with hexyl cinnamic aldehyde in acetone:olive oil (4+1) using CBA/CaOlaHsd mice in May 2007. The stimulation index was 4.88 for the highest concentration of the postive control (25% w/v).
- Key result
- Parameter:
- SI
- Value:
- 2.54
- Variability:
- SD= 0.88
- Test group / Remarks:
- 25% (w/v) of the test item
- Key result
- Parameter:
- SI
- Value:
- 2.65
- Variability:
- SD= 1.09
- Test group / Remarks:
- 10% (w/v) of the test item
- Key result
- Parameter:
- SI
- Value:
- 1.54
- Variability:
- SD= 0.52
- Test group / Remarks:
- 5% (w/v) of the test item
- Key result
- Parameter:
- SI
- Value:
- 1
- Variability:
- SI normalized (1), calculated from number of radioactive disintegrations per minute (DPM) per lymph node: 538.5 ± 176.6
- Test group / Remarks:
- control group (vehicle dimethyl formamide)
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION
The proliferative response of lymph node cells is expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of 3HTdR incorporated into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes (stimulation index). Before DPM/node values were determined, mean scintillation-background DPM was subtracted from test and control raw data.
EC3 CALCULATION
The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3.
CLINICAL OBSERVATIONS
No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.
BODY WEIGHTS
The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item was found to be not a skin sensitiser in a LLNA according to OECD guideline 429.
- Executive summary:
In the study according to OECD guideline 429, the test item dissolved in dimethyl formamide was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay was performed using test item concentrations of 5, 10, and 25%. All treated animals survived the scheduled study period and no signs of toxicity were observed. A relevant increase in ear thickness gain could not be observed after treatment with the test item. In this study Stimulation Indices (S.I.) of 1.54, 2.65, and 2.54 were determined with the test item at concentrations of 5, 10, and 25% in dimethyl formamide, respectively. The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3. The test item was not a skin sensitiser in this assay.
Reference
Table 1: Calculation and results of individual data
Test item concentration |
Measurement |
Calculation |
Result |
Calculation |
DPM per lymph node b) |
Result |
|
% (w/v) |
Group |
DPM |
DPM-BG per anima (2 lymph nodes) a) |
S.I. |
number of lymph nodes |
S.I. |
|
— |
BG I |
16.00 |
— |
— |
— |
— |
— |
— |
BG II |
18.00 |
— |
— |
— |
— |
— |
— |
1_1 |
822.00 |
805.0 |
— |
— |
— |
— |
— |
1_2 |
1636.00 |
1619.0 |
— |
— |
— |
— |
— |
1_3 |
1094.00 |
1077.0 |
— |
— |
— |
— |
— |
1_4 |
741.00 |
724.0 |
— |
— |
— |
— |
— |
1_5 |
1177.00 |
1160.0 |
— |
10 |
538.5 |
1.00 |
5 |
2_1 |
1183.00 |
1166.0 |
1.1 |
— |
— |
— |
5 |
2_2 |
2032.00 |
2015.0 |
1.9 |
— |
— |
— |
5 |
2_3 |
1030.00 |
1013.0 |
0.9 |
— |
— |
— |
5 |
2_4 |
2237.00 |
2220.0 |
2.1 |
— |
— |
— |
5 |
2_5 |
1877.00 |
1860.0 |
1.7 |
10 |
827.4 |
1.54 |
10 |
3_1 |
4752.00 |
4735.0 |
4.4 |
— |
— |
— |
10 |
3_2 |
2789.00 |
2772.0 |
2.6 |
— |
— |
— |
10 |
3_3 |
2699.00 |
2682.0 |
2.5 |
— |
— |
— |
10 |
3_4 |
1574.00 |
1557.0 |
1.4 |
— |
— |
— |
10 |
3_5 |
2536.00 |
2519.0 |
2.3 |
10 |
1426.5 |
2.65 |
25 |
4_1 |
2015.00 |
1998.0 |
1.9 |
— |
— |
— |
25 |
4_2 |
2271.00 |
2254.0 |
2.1 |
— |
— |
— |
25 |
4_3 |
3537.00 |
3520.0 |
3.3 |
— |
— |
— |
25 |
4_4 |
3979.00 |
3962.0 |
3.7 |
— |
— |
— |
25 |
4_5 |
1973.00 |
1956.0 |
1.8 |
10 |
1369.0 |
2.54 |
Vehicle: dimethyl formamide
BG = Background (1 mL 5% trichloroacetic acid) in duplicate
1 = Control Group
2-4 = Test Group
S.I. = Stimulation Index
= The mean of the background value (BGI and BGII) was subtracted from the value. = DPM/node was determined by dividing the sum of the measured values from all lymph nodes within a group by the number of lymph nodes taken from that group
Table 2: Results for ear thickness
Animal No. |
Dose Group |
Ear thickness before the 1st application (Dm) |
Ear thickness prior to treatment with 3HTdR (Dm) |
Ear thickness gain (Dm) |
|||||||
right |
left |
mean |
Mean dose group ± SD |
right |
left |
mean |
Mean dose group ± SD |
Thickness gain |
Mean dose group ± SD |
||
1 |
|
220 |
240 |
230 |
|
290 |
290 |
290 |
|
60 |
|
2 |
|
250 |
250 |
250 |
|
260 |
290 |
275 |
|
25 |
|
3 |
|
240 |
240 |
240 |
|
240 |
270 |
255 |
|
15 |
|
4 |
|
250 |
260 |
255 |
|
250 |
280 |
265 |
|
10 |
|
5 |
|
230 |
240 |
235 |
242 ± 11 |
240 |
240 |
240 |
265 ± 22 |
5 |
23 ± 22 |
6 |
2 |
250 |
250 |
250 |
|
260 |
270 |
265 |
|
15 |
|
7 |
2 |
250 |
250 |
250 |
|
250 |
250 |
250 |
|
0 |
|
8 |
2 |
265 |
250 |
258 |
|
280 |
270 |
275 |
|
18 |
|
9 |
2 |
240 |
250 |
245 |
|
270 |
280 |
275 |
|
30 |
|
10 |
2 |
240 |
250 |
245 |
250 ± 7 |
260 |
270 |
265 |
266 ± 11 |
20 |
17 ± 11 |
11 |
3 |
260 |
270 |
265 |
|
270 |
280 |
275 |
|
10 |
|
12 |
3 |
240 |
240 |
240 |
|
250 |
250 |
250 |
|
10 |
|
13 |
3 |
230 |
240 |
235 |
|
280 |
260 |
270 |
|
35 |
|
14 |
3 |
250 |
260 |
255 |
|
260 |
260 |
260 |
|
5 |
|
15 |
3 |
250 |
240 |
245 |
248 ± 12 |
250 |
250 |
250 |
261 ± 12 |
5 |
13 ± 13 |
16 |
4 |
250 |
260 |
255 |
|
250 |
280 |
265 |
|
10 |
|
17 |
4 |
250 |
240 |
245 |
|
260 |
260 |
260 |
|
15 |
|
18 |
4 |
230 |
240 |
235 |
|
250 |
270 |
260 |
|
25 |
|
19 |
4 |
250 |
250 |
250 |
|
280 |
270 |
275 |
|
25 |
|
20 |
4 |
250 |
240 |
245 |
246 ± 8 |
270 |
260 |
265 |
265 ± 11 |
20 |
19 ± 7 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitisation, key study
In the study according to OECD guideline 429, the test item dissolved in dimethyl formamide was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay was performed using test item concentrations of 5, 10, and 25%. All treated animals survived the scheduled study period and no signs of toxicity were observed. A relevant increase in ear thickness gain could not be observed after treatment with the test item. In this study Stimulation Indices (S.I.) of 1.54, 2.65, and 2.54 were determined with the test item at concentrations of 5, 10, and 25% in dimethyl formamide, respectively. The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3. The test item was not a skin sensitiser in this assay.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data the test item is not classified as skin sensitising according to Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217.
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.