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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 939-579-8 | 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
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:
- weight of evidence
- Study period:
- 28 February - 20 March 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study conducted in compliance with OECD guideline 429 without any deviation
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- version of April 24th, 2004
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 10 weeks
- Weight at study initiation: 20.7 ± 1.1 g
- Housing: Individually in disposable crystal polystyrene cages
- Diet (e.g. ad libitum): SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water (e.g. ad libitum): Tap water (filtered using a 0.22 µ filter), ad libitum
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light - Vehicle:
- methyl ethyl ketone
- Remarks:
- Batch No 31125-303 from Aldrich, Saint-Quentin-Fallavier, France
- Concentration:
- Main experiment: 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v)
- No. of animals per dose:
- Preliminary tests: One female/dose
Main experiment: Four females/dose - Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: Due to the unsatisfactory solubility of the test item in the first recommended vehicle (acetone/olive oil (4/1, v/v)) and dimethylformamide, methyl ethyl ketone was chosen from the other proposed vehicles.
- Irritation and lymph node proliferation response: A preliminary test was performed as follows: the test item was prepared at the concentrations of 10, 25, 50 and 100 % (w/v) in the first assay and at 1, 2.5, 5 and 10 % (w/v) in the complementary assay. For 3 consecutive days, the animals received applications of 25 μL of the dosage form preparations to the external surface of both ears (one concentration per ear). A gentle massage was performed in order to facilitate the application of the undiluted test item only. Measurement of the ear thickness (using a micrometer) was performed each day before treatment and 24 h after the application (first assay), or 72 h after the last application (complementary assay).
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: The test item was considered as a skin sensitizer when the SI for a dose group is ≥ 3. Other relevant criteria such as cellularity, radioactivity levels and ear thickness were also taken into account for the interpretation of results.
TREATMENT PREPARATION AND ADMINISTRATION: 25 µL of test material at concentrations of 0 (vehicle control), 0.1, 0.25, 0.5, 1.0, 2.5 % (w/v) in methyl ethyl ketone were applied to the dorsal surface of each ear on Days 1, 2 and 3. On Day 6, 250 μL of 0.9 % NaCl containing 20 μCi of [3H] methyl-thymidine (specific activity: 25 Ci/mmol) was injected into the tail vein of each experimental mouse. Five hours later, all mice were killed by cervical dislocation and the draining auricular lymph node of each ear was excised. A single cell suspension of auricular lymph node cells (ALNC) was prepared by mechanical disaggregation in Petri dishes with the plunger of a syringe. Cell suspensions were washed with 15 mL of 0.9 % NaCl and pellets obtained were re-suspended in 0.9 % NaCl for numeration of lymphocytes (cellularity) and determination of their viability by exclusion of trypan blue. Each cell suspension was then centrifuged and pellets were precipitated with 3 mL of 5 % (w/v) trichloroacetic acid (TCA) in purified water at +4 °C overnight. After a last centrifugation, the pellets were precipitated with 1 mL of 5 % TCA. Three mL of Ultima GoldxR scintillation fluid (Packard) were added in order to measure incorporation of 3H-TdR using β-scintillation counting. The results were expressed as disintegrations per min (dpm) per group and per node and Stimulation Indices (SI) were calculated. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- No data
- Positive control results:
- - Mean DPM = 3776.29
- Stimulation index = 23.94 - Parameter:
- SI
- Value:
- 0.78
- Test group / Remarks:
- 0.1% (w/v)
- Parameter:
- SI
- Value:
- 2.04
- Test group / Remarks:
- 0.25% (w/v)
- Parameter:
- SI
- Value:
- 4.42
- Test group / Remarks:
- 4.42% (w/v)
- Parameter:
- SI
- Value:
- 10.95
- Test group / Remarks:
- 1.0% (w/v)
- Parameter:
- SI
- Value:
- 22.25
- Test group / Remarks:
- 2.5% (w/v)
- Interpretation of results:
- sensitising
- Conclusions:
- Under the test conditions, CHIMEXANE HB is classified as ‘R43 May cause sensitisation by skin contact’, according to the criteria of Annex VI to the Directive 67/548/EEC and ‘Category 1’ according to the CLP Regulation (EC) N° (1272-2008).
- Executive summary:
In a GLP-compliant local lymph node assay performed according to OECD guideline 429, CBA/J mice (4 females/dose) received 25 µL of CHIMEXANE HB at concentrations of 0 (vehicle control), 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) in methyl ethyl ketone or of the positive control (alpha-hexylcinnamaldehyde (25 % v/v) in methyl ethyl ketone) to the dorsal surface of each ear for three consecutive days. On Day 6, all animals were injected with [3H] methyl-thymidine and after five hours the draining (auricular) lymph nodes were excised and measured for radioactivity expressed as a number of disintegrations per minute (DPM).
Mean DPM for 0, 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) CHIMEXANE HB were 157.71, 122.55, 322.11, 697.54, 1726.5 and 3508.91, respectively. Stimulation index for 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) CHIMEXANE HB were 0.78, 2.04, 4.42, 10.95 and 22.25, respectively. The estimated concentration giving rise to a 3 fold increase in lymphocyte proliferation (EC3) was 0.35 % (w/v).
An erythema was noted on Day 6 in 1/4 animals at the concentration of 0.1 % and, in association with dryness of the skin, in all animals at the concentration of 2.5 %. No increase in ear thickness was observed in the animals of the treated groups. As a moderate increase in cellularity and a stimulation index > 3 (SI = 23.94) were noted in the postive control group, the study was considered valid.
Under the test conditions, CHIMEXANE HB is classified as ‘R43 May cause sensitisation by skin contact’, according to the criteria of Annex VI to the Directive 67/548/EEC and ‘Category 1’ according to the CLP Regulation (EC) N° (1272-2008).
Reference
Preliminary test:
Test item was found to be irritant in the first preliminary test at the concentrations of 10, 25, 50 and 100 % (w/v). A complementary preliminary test was therefore performed at the following lower concentrations: 1, 2.5, 5 and 10 % (w/v). In the complementary preliminary test, the test item was irritant at the concentrations of 5 and 10 % (w/v). The highest tested concentration retained for the main test was therefore 2.5 % (w/v).
Main test:
- Clinical examinations: No mortality and no clinical signs were observed during the study. The body weight change of treated animals was similar to that of control animals.
- Local irritation: An erythema was noted on Day 6 in 1/4 animals at the concentration of 0.1 % (w/v) and, in association with dryness of the skin, in all animals at the concentration of 2.5 % (w/v). No increase in ear thickness was observed in the animals of the treated groups.
Table 7.4.1: Results of skin sensitization:
Treatment and concentrations |
No. of nodes per group |
dpm per group |
dpm per node |
Stimulation index (SI) |
Increase in ear thickness (% between Day 1 and Day 6) |
Irritation level |
EC3 value |
Vehicle |
8 |
157.71 |
19.71 |
- |
-0.98 |
- |
- |
0.1 % |
8 |
122.55 |
15.32 |
0.78 |
-1.98 |
I |
0.35% |
0.25 % |
8 |
322.11 |
40.26 |
2.04 |
2.04 |
||
0.5 % |
8 |
697.54 |
87.19 |
4.42 |
4.42 |
||
1.0 % |
8 |
1726.50 |
215.81 |
10.95 |
0.99 |
||
2.5% |
8 |
3508.91 |
438.61 |
22.25 |
1.92 |
||
HCA 25 % |
8 |
3776.29 |
472.04 |
23.94 |
- |
- |
- |
dpm = disintegrations per minute
I = non-irritant (increase in ear thickness < 10 %)
HCA = α-hexylcinnamaldehyde
EC3 value = theoretical concentration resulting in a SI value of
stimulation index = dpm of treated group / dpm of control group
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
In a GLP-compliant local lymph node assay performed according to OECD guideline 429 in 2009, CBA/J mice (4 females/dose) received 25 µL of either the test item 1667, the vehicle alone (acetone/olive oil (4/1, v/v)) or the positive control (Alpha-hexylcinnamaldehyde 25% (v/v) in acetone/olive oil (4/1, v/v)) on the dorsal surface of each ear for three consecutive days in two independent experiments. In experiment 1, the test item was tested at the concentrations of 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v); and at the concentrations of 0.25, 0.5, 1.0, 1.5 and 2.5 % (w/v) in experiment 2. On Day 6, all animals were injected with [3H] methyl-thymidine and after five hours the draining (auricular) lymph nodes were excised and measured for radioactivity expressed as a number of disintegrations per minute (DPM).
In both experiments, no mortality and no clinical signs were observed during the study. Animal body weight was not affected by treatment. In the positive control group, a moderate increase in cellularity and a stimulation index > 3 (SI = 23.94) were noted. The study was therefore considered valid.
In experiment 1, stimulation indices were 0.90, 0.46, 2.94, 2.21 and 6.73 at 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) test material, respectively. An erythema and a dryness of the skin of the ears were noted in all the animals treated at the concentration of 2.5 % (w/v). A slightly increase in ear thickness was observed in these animals. In experiment 2, stimulation indexes were 1.07, 1.66, 2.03, 6.24 and 6.54 at 0.25, 0.5, 1.0, 1.5 and 2.5 % (w/v) test material, respectively. A dryness of the skin was noted on Day 6 in 2/4 animals treated at the concentration of 0.5 % (w/v) and in all the animals treated at the concentration of 1 and 1.5 % (w/v). An erythema and a dryness of the skin of the ears were noted in all the animals treated at the concentration of 2.5 % (w/v). A slightly increase in ear thickness was observed in these animals. The EC3 values in experiments 1 and 2 were calculated to be 1.3 and 1.1 % (w/v), respectively.
In another GLP-compliant local lymph node assay performed according to OECD guideline 429 in 2006, groups of CBA/J mice (4 females/dose) received 25 µL of CHIMEXANE HB at concentrations of 0 (vehicle control), 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) in methyl ethyl ketone or of the positive control (alpha-hexylcinnamaldehyde (25 % v/v) in methyl ethyl ketone) to the dorsal surface of each ear for three consecutive days. On Day 6, all animals were injected with [3H] methyl-thymidine and after five hours the draining (auricular) lymph nodes were excised and measured for radioactivity expressed as a number of disintegrations per minute (DPM).
No clinical signs and no mortality were observeed during the study. Stimulation index for 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) CHIMEXANE HB were 0.78, 2.04, 4.42, 10.95 and 22.25, respectively. The estimated concentration giving rise to a 3 fold increase in lymphocyte proliferation (EC3) was 0.35 % (w/v). An erythema was noted on Day 6 in 1/4 animals at the concentration of 0.1 % and, in association with dryness of the skin, in all animals at the concentration of 2.5 %. No increase in ear thickness was observed in the animals of the treated groups. As a moderate increase in cellularity and a stimulation index > 3 (SI = 23.94) were noted in the postive control group, the study was considered valid.
Migrated from Short description of key information:
In two LLNA, Chimexane HB induced skin sensitization with EC3 values of 0.35% and 1.1%.
Justification for selection of skin sensitisation endpoint:
GLP-compliant study with a Klimish 1, which presents the lowest EC3 value.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
As Chimexane HB induced positive responses in two LLNA with EC3 values of 0.35% and 1.1%, it is classified "R43: May cause sensitisation by skin contact" according to the Annex VI to the Directive 67/548/EEC and skin sensitiser Category 1 according to the Regulation (EC) N° 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.