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EC number: 449-360-4 | CAS number: 647828-16-8
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 June 2003 to 01 July 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- -
- EC Number:
- 449-360-4
- EC Name:
- -
- Cas Number:
- 647828-16-8
- Molecular formula:
- C18H32O
- IUPAC Name:
- decahydro-2,2,6,6,7,8,8-heptamethyl-2H-Indeno[4,5-b] furan
- Test material form:
- liquid
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/Ca (CBA/Ca CruBR)
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS:
- Source: Charles River UK Limited, Margate, Kent, UK
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 15 to 23 g
- Housing: Individually in suspended solid-floor polypropylene cages furnished with softwood woodflakes
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): was approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06.00 to 18.00) and 12 hours darkness
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 100, 50 and 25 %
- No. of animals per dose:
- 5
- Details on study design:
- ANIMAL ASSIGNMENT AND TREATMENT:
- Name of test method: Local Lymph Node Assay in the Mouse (LLNA) - individual animal approach
- Criteria used to consider a positive response: Stimulation Index (SI) of 3.0 or greater
TREATMENT PREPARATION AND ADMINISTRATION:
- Dose selection: Available information suggested that the test substance would not produce systemic toxicity or excessive local irritation at the highest suitable concentration.
- Preparation of Test Substance: The test substance was used undiluted and freshly prepared in acetone/olive oil 4:1.
- Choice of vehicle: Acetone/olive oil 4:1 produced the highest concentration that was suitable for dosing.
- Analysis of Test Substance: Determination, by analysis, of the concentration, homogeneity and stability of the test substance preparations was not appropriate because it was not specified in the Study Plan and is not a requirement of the Test Guideline.
- Test Substance Administration: The mice were treated by daily application of 25 µL of the appropriate concentration of the test substance or the vehicle alone to the dorsal surface of each ear for 3 consecutive days (Days 1, 2, 3). The test substance formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
- 3H-Methyl Thymidine Administration: Five days following the first topical application of the test substance (Day 6) all mice were injected via the tail vein with 250 µL of phosphate buffered saline containing 3H-methyl thymidine 3HTdR:80µCi/mL, specific activity 2.0 Ci/mmol, giving a total of 20 µCi to each mouse. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Data were processed to give group mean values for dpm and standard deviations where appropriate. Individual and group mean dpm values were assessed for dose response relationships by linear regression analysis followed by one way analysis of variance (ANOVA) incorporating Levene's test for homogeneity of variance. Where variances were shown to be homogenous pair wise comparisons were conducted using Dunnett's test.
Results and discussion
- Positive control results:
- The Stimulation Index (SI) expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group were determined to be 2.0 at 5 % v/v, 1.9 at 10 % v/v, and 6.8 at 25 % v/v. Therefore, alpha-Hexylcinnamaldehyde, Tech 85 % was considered to be a sensitiser under the conditions of the test.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- EC3
- Value:
- 43.44
- Parameter:
- SI
- Value:
- 1.35
- Remarks on result:
- other: 25 %
- Parameter:
- SI
- Value:
- 3.18
- Remarks on result:
- other: 50 %
- Parameter:
- SI
- Value:
- 6.32
- Remarks on result:
- other: 100%
Any other information on results incl. tables
Clinical Observations and Mortality:
No mortality or signs of systemic toxicity were noted in the test or control animals during the study. Individual clinical observations and mortality data for test and control animals are given In Table 2.
Body Weight:
Body weight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period. Individual body weights and body weight changes for test and control animals are given in Table 3.
EC3 Value:
An EC3 value of 43.44 % was calculated using this equation: EC3 = c + [[(3 -d)/(b-d)] x (a-c)] (with a = lowest concentration giving stimulation index >3, b = actual stimulation index caused by 'a', c = highest concentration failing to produce a stimulation index of 3, and d = actual stimulation index caused by 'c')
Concentration |
Animal Number |
dpm/ |
Mean dpm/Animal |
Stimulation Index (SI)b |
Result |
Vehicle |
1-1 |
1924.82 |
1766.62 |
N/A |
N/A |
1-2 |
2250.40 |
||||
1-3 |
1390.26 |
||||
1-4 |
1784.06 |
||||
1-5 |
1483.57 |
||||
25 |
2-1 |
1312.38 |
2377.93 |
1.35 |
Negative |
2-2 |
1499.26 |
||||
2-3 |
2378.80 |
||||
2-4 |
2145.82 |
||||
2-5 |
4553.37 |
||||
50 |
3-1 |
4415.68 |
5623.16** |
3.18 |
Positive |
3-2 |
5859.02 |
||||
3-3 |
4412.52 |
||||
3-4 |
6865.30 |
||||
3-5 |
6563.29 |
||||
100 |
4-1 |
7027.93 |
11157.90* |
6.32 |
Positive |
4-2 |
13472.95 |
||||
4-3 |
14747.63 |
||||
4-4 |
11822.04 |
||||
4-5 |
8718.93 |
a = Total number of lymph nodes per animal is 2
b = Stimulation Index of 3.0 or greater indicates a positive result
N/A = Not applicable
* = Significantly different from control group p<0.05
** = Significantly different from control group p<0.01
Table 2. Individual Clinical Observations and Mortality Data.
Concentration (% w/w) in acetone/olive oil 4:1 |
Animal Number |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
|||
Pre-dose |
1 hr post dose |
Pre-dose |
1 hr post dose |
Pre-dose |
1 hr post dose |
|||||
Vehicle |
1-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
25 |
2-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
50 |
3-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
100 |
4-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 = No signs of systemic toxicity
Table 3. Individual Body Weights and Body Weight Changes.
Concentration (% w/w) in acetone/olive oil 4:1 |
Animal Number |
Body Weight Change (g) |
Body Weight Change (g) |
|
Day 1 |
Day 6 |
|||
Vehicle |
1-1 |
19 |
20 |
1 |
1-2 |
20 |
21 |
1 |
|
1-3 |
18 |
18 |
0 |
|
1-4 |
17 |
19 |
2 |
|
1-5 |
18 |
19 |
1 |
|
25 |
2-1 |
18 |
19 |
1 |
2-2 |
17 |
19 |
2 |
|
2-3 |
18 |
19 |
1 |
|
2-4 |
21 |
21 |
0 |
|
2-5 |
17 |
17 |
0 |
|
50 |
3-1 |
18 |
19 |
1 |
3-2 |
19 |
20 |
1 |
|
3-3 |
18 |
19 |
1 |
|
3-4 |
17 |
18 |
1 |
|
3-5 |
19 |
19 |
0 |
|
100 |
4-1 |
19 |
21 |
2 |
4-2 |
18 |
18 |
0 |
|
4-3 |
20 |
20 |
0 |
|
4-4 |
18 |
19 |
1 |
|
4-5 |
20 |
20 |
0 |
Applicant's summary and conclusion
- Interpretation of results:
- other: Substance is a skin sensitiser (1B) according to EU CLP (1272/2008)
- Conclusions:
- The substance is a skin sensitiser (1B) in the LLNA test, OECD guideline 429.
- Executive summary:
A Local Lymph Node Assay (LLNA) was performed in accordance with OECD TG 429 and under GLP conditions to assess the skin sensitisation potential of the test substance in the CBA/Ca strain mice following topical application to the dorsal surface of the ear. Three groups, each of five animals, were treated with 50 µL (25 µL per ear) of the undiluted test material (100 %) and the test substance as a solution in acetone/olive oil 4:1 at concentrations of 50 % and 25 % v/v. A further group of five animals was treated with acetone/olive oil 4:1 alone. The Stimulation Index (SI) expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group were 1.35, 3.18, and 6.32 for the 25 %, 50 %, and 100 % exposure groups, respectively. The calculated EC3 value was 43.44 %. Based on these results, the test substance was considered to be a sensitiser (1B) under the conditions of the test.
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