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EC number: 944-461-4 | CAS number: -
- 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 (LLNA): not sensitising
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:
- 25 Jan - 11 Feb 2010
- 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 Jul 2010
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United Kingdom, UK
- Type of study:
- mouse local lymph node assay (LLNA)
- Justification for non-LLNA method:
- Test was done before LLNA as first-choice method for in-vivo testing was set into force.
- Species:
- mouse
- Strain:
- other: CBA/CA (CBA/CaOlaHsd)
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Bicester, UK
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 16 - 22 g
- Housing: the animals were individually housed in suspended solid-floor polypropylene cages furnished with softwood woodflakes
- Diet: 2014 Teklad Global Rodent diet (Harlan Teklad, Bicester, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- dimethylformamide
- Concentration:
- 5, 10 and 25% w/w
- No. of animals per dose:
- 5 females
- Details on study design:
- RANGE FINDING TESTS: in the preliminary screening test, 1 mouse was treated by daily application of 25 µL of the test substance at the maximum attainable concentration of 25% w/w in dimethylformamide, to the dorsal surface of each ear for 3 consecutive days (Day 1 - 3). The mouse was observed twice daily on Day 1 - 3 and once daily on Day 4 - 6. The body weight was recorded on Day 1 (prior to dosing) and on Day 6. No signs of systemic toxicity were reported and no adverse effects on body weight were noted.
- Compound solubility: the solubility of the test substance was assessed by mixing the test substance to a dilution of 25 and 50% with acetone/olive oil (4:1), dimethyl formamide, butanone, dimethyl sulphoxide, acetone, ethanol/distilled water (7:3) and 1% pluronic L92 in distilled water, respectively. The most suitable vehicle was used in the range-finding and main study.
- Irritation: there were no signs of irritation in the treated skin area.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: ³H-methyl thymidine incorporation determined by ß-scintillation
- Criteria used to consider a positive response: if the results indicate a SI ≥ 3, the test substance is considered to be a skin sensitiser
TREATMENT PREPARATION AND ADMINISTRATION:
A formulation of the test substance in dimethyl formamide was prepared within 2 hours before application. 25 µL was applied with a micropipette to the dorsal surface of both ears of the mice for 3 consecutive days. On Day 6, each animal was injected via the tail vein with 0.25 mL phosphate buffered saline containing 20 µCi of ³H-methyl thymidine (ARC UK Ltd., UK). After approximately 5 hours, the mice were sacrificed and the draining lymph nodes of the ears were excised. 1 mL PBS was added to the nodes of each animal and the nodes were processed per animal. A single cell suspension of lymph node cells was prepared in PBS by gentle mechanical disaggregation through a stainless steel gauze (diameter 200 µm). Lymph node cells were washed twice with an excess of PBS and the DNA precipitated with 5% trichloroacetic acid (TCA) at 4 ºC for approximately 18 hours. The precipitate was recovered by centrifugation, resuspended in 1 mL TCA and transferred to 10 mL Optiphase Trisafe as the scintillation fluid. The number of Disintegrations Per Minute (DPM) was measured using a Beckman LS6500 scintillation system (Beckman Instruments Inc., Fullerton, USA). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Data was processed to give group mean values for disintegrations per minute and standard deviations where appropriate. Individual and group mean disintegrations per minute values were assessed for dose response relationships by analysis of homogeneity of variance followed by one-way analysis of variance (ANOVA). In the event of a significant result from the ANOVA, pairwise comparisons were performed between control and treated groups. For homogenous datasets Dunnett’s Multiple Comparison test was used and for non-homogenous datasets Dunnett’s T3 Multiple Comparison Method was used.
- Positive control results:
- The Stimulation Index for the positive control group used in the study was 6.46.
In addition, reliability checks are regularly performed by the testing laboratory in order to check the sensitivity of the test system and the reliability of the experimental techniques applied. The historical results were given in the study report. In November 2009 a study was performed (project number 0039/1116), in which groups of 5 female CBA mice were exposed to 15% alpha-hexylcinnamaldehyde in dimethyl formamide or the vehicle alone. The SI value for the positive control group was 5.16, showing the validity of the study. - Key result
- Parameter:
- SI
- Value:
- >= 1.13 - <= 1.45
- Test group / Remarks:
- Test group 5, 10 and 25%
- Key result
- Parameter:
- other: disintegrations per minute (DPM)
- Value:
- >= 350 - <= 471
- Test group / Remarks:
- Test group 5, 10 and 25%
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION
The Stimulation Index for the 5, 10 and 25% groups was 1.13, 1.45 and 1.34, respectively (see Table 1 and 2 under 'Ant other information on results incl. tables'). The mean DPM/animal values for the 5, 10 and 25% groups were 350, 389 and 471, respectively. The mean DPM/animal value for the control group was 352.
CLINICAL OBSERVATIONS:
No clinical signs were observed.
BODY WEIGHTS
The body weights and body weight gains were comparable between the control and the treatment groups. - Interpretation of results:
- other: not classified
Reference
Table 1: Radioactivity measurements, individual results
Dose group (%) |
Animal |
DPM/animal |
Vehicle control |
1 |
1306.85 |
Vehicle control |
2 |
1425.22 |
Vehicle control |
3 |
1781.19 |
Vehicle control |
4 |
764.77 |
Vehicle control |
5 |
812.59 |
5 |
1 |
1672.19 |
5 |
2 |
1102.57 |
5 |
3 |
1107.50 |
5 |
4 |
1489.06 |
5 |
5 |
1539.24 |
10 |
1 |
2257.42 |
10 |
2 |
1759.47 |
10 |
3 |
1833.76 |
10 |
4 |
1620.48 |
10 |
5 |
1358.38 |
25 |
1 |
1976.34 |
25 |
2 |
1442.97 |
25 |
3 |
1526.26 |
25 |
4 |
1809.78 |
25 |
5 |
1425.67 |
Positive control |
1 |
9207.36 |
Positive control |
2 |
12528.48 |
Positive control |
3 |
6388.06 |
Positive control |
4 |
6475.71 |
Positive control |
5 |
4719.74 |
Table 2: Disintegrations per minute (DPM) and stimulation index (SI)
Dose group (%) |
DPM (mean ± SD) |
SI |
Vehicle control |
1218.12 ± 429.47 |
1.0 |
5 |
1382.11 ± 261.64 |
1.13 |
10 |
1765.90 ± 329.19 |
1.45 |
25 |
1636.20 ± 244.73 |
1.34 |
Positive control |
7863.87 ± 3064.07 |
6.46 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
The skin sensitising potential of Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene was evaluated in a local lymph node assay (LLNA) performed according to OECD guideline 429 and under GLP conditions (Sanders, 2010). 25 µl of a 5, 10 and 25% w/w suspension of test substance in dimethylformamide was applied to the dorsal surface of both ears of 5 CBA mice/dose for 3 consecutive days. On Day 6, each animal was injected via the tail vein with 0.25 mL phosphate buffered saline containing 20 µCi of ³H-methyl thymidine. After approximately 5 hours, the mice were sacrificed and the draining lymph nodes of the ears were excised. The nodes of each animal were processed individually. PBS was added to the nodes and DNA was precipitated with 5% TCA at 4 °C for 18 hours. The number of disintegrations per minute (DPM) was determined by beta-scintillation count. The positive control group (hexyl cinnamic aldehyde) was treated concomitantly and shown to be valid. The mean DPM/animal values for the control, 5, 10 and 25% group were 352, 350, 389 and 471, respectively. The stimulation index (SI) calculated for the 5, 10 and 25% group was 1.13, 1.54 and 1.34, respectively. The SI was lower than 3 at all dose levels; therefore the test substance is considered to be not skin sensitising.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.
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