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EC number: 945-069-6 | 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
In a test according to OECD 406 (Buehler) 20 female guinea pigs were exposed to the undiluted Bis(2-ethylhexyl) azelate on day 0, 6 and 13 during 6 hours epicutaneously under occlusion (Phycher 2017). A group of 10 female guinea pigs received a similar treatment with liquid paraffin on day 0, 6 and 13. Both groups were challenged with undiluted substance on day 26 during 6 hours epicutaneously under occlusion and were checked 24, 48 and 72 hours thereafter for signs of skin reaction.
In the treated group (treatment dose of 100%), no macroscopic cutaneous reactions attributable to allergy were observed during the examination following the removal of the occlusive dressing.
In the control group (associated with the treatment dose of 100%), no cutaneous intolerance reactions were observed during the examination following the removal of the occlusive dressing.
The skin sensitising potential of Bis(2-ethylhexyl) azelate (CAS 103-24-2) was investigated in a Local Lymph Node Assay (LLNA) in mice according to OECD guideline 429 and in compliance with GLP (Bradshaw, 2012).
Based on a range-finding test in one female CBA/CaOlaHsd mouse, the undiluted test substance (100%) and concentrations of 25% and 50% (v/v) in acetone/olive oil (4:1 v/v) were selected for the treatment of mice in the main study. In this experiment, 4 female CBA/CaOlaHsd mice per test group were treated with the test substance or vehicle alone, respectively. The test substance or the vehicle were applied on the external surface of each ear (25 µL/ear) for three consecutive days. Five days after the first topical application, the cell proliferation of pooled lymph nodes per group was measured by incorporation of ³H-methyl thymidine and expressed as the amount of radioactive disintegration per minute (DPM). The DPM/lymph node for each test group were 5244.83, 5178.42 and 8048.58 at concentrations of 25%, 50% and 100% of the test substance, respectively. For the control group, a DPM/lymph node of 1553.82 was determined. Based on these results, stimulation indices of 3.38, 3.33 and 5.18 were calculated for treatment concentrations of 25%, 50% and 100%, respectively. No local or systemic toxicity and no effects on body weights were observed.
The reactivity of the substance towards synthetic cysteine (C)- or lysine (K)-containing peptides was evaluated in the Direct Peptide Reactivity Assay (DPRA). For this purpose the test substance was incubated with synthetic peptides for ca. 24 hours at room temperature and the remaining non-depleted peptide concentrations were determined by high performance liquid chromatography (HPLC) with gradient elution and UV-detection at 220 nm (BASF 2014).
The mean C-peptide depletion, caused by the test substance was determined to be 0.52%.
The mean K-peptide depletion, caused by the test substance was determined to be -1.05%.
The substance is considered non-sensitizing under the conditions of the test.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20 February 2017 to 30 March 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- The results of in vitro assays are indicative for no sensitization, but an LLNA test showed ambiguous results. Therefore in order to exclude false positive results in the LLNA test this additional in vivo test was performed.
The standard study plan related to this study was approved by the registered Ethics Committee No. 76. - Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: ENVIGO (Kreuzelweg 53, 5961 NM HORST The Netherlands
- Age at study initiation: 3-4 weeks
- Weight at study initiation: 270-306 g
- Housing: groups of maximum 3 in polycarbonate cages.
- Diet: ENVIGO, 2040C ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ° C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- epicutaneous, occlusive
- Vehicle:
- other: liquid paraffin
- Remarks:
- 50% gave colorless solution
- Concentration / amount:
- 100%
- Day(s)/duration:
- 6
- Adequacy of induction:
- highest technically applicable concentration used
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: liquid paraffin
- Concentration / amount:
- 100%
- Day(s)/duration:
- 6 hours
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 20 treatment and 10 controls
- Details on study design:
- RANGE FINDING TESTS:
Three guinea pigs were treated with the test item placed onto the selected treatment sites and covered with an occlusive dressing for a period of 6 hours at 4 different concentrations: 100%, and diluted at 75%, 50% and 25% in liquid paraffin.
Washing of the skin after removal of the dressing was done with liquid paraffin.
maximal non-irritant concentration was 100%
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours (on day 0, 6 and 13)
- Test groups: 20 females treated with 0.5 mL 100% undiluted substance
- Control group: 10 females treated with 0.5 mL liquid paraffin
- Site: scapular zone
- Frequency of applications: 3 times
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 26
- Exposure period: 6 hours
- Test groups: 20 females treated with 0.5 mL 100% undiluted substance
- Control group: 10 females treated with 0.5 mL 100% undiluted substance
- Site: dorso-lumbar zone of the left flank
- Evaluation (hr after challenge): at 24, 48 and 72 hour
- Challenge controls:
- 0.5 mL of liquid paraffin was applied on the right flank.
- Positive control substance(s):
- yes
- Remarks:
- α-Hexylcinnamaldehyde in 3 separate tests
- Positive control results:
- positive in 3 applications
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0 (100% in challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100% (100% in challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0 (challenge 100%)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100% (100% in challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 0 (100% challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 100% (100% in challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In a Buehler test the substance was not sensitizing to the skin.
- Executive summary:
In a test according to OECD 406 (Buehler) 20 female guinea pigs were exposed to the undiluted substance on day 0, 6 and 13 during 6 hours epicutaneously under occlusion. A group of 10 female guinea pigs received a similar treatment with liquid paraffin on day 0, 6 and 13. Both groups were challenged with undiluted substance on day 26 during 6 hours epicutaneously under occlusion and were checked 24, 48 and 72 hours thereafter for signs of skin reaction.
In the treated group (treatment and challenge dose of 100%), no macroscopic cutaneous reactions attributable to allergy were observed during the examination following the removal of the occlusive dressing.
In the control group (associated with the challenge dose of 100%), no cutaneous intolerance reactions were observed during the examination following the removal of the occlusive dressing.
No cutaneous reaction was recorded in animals from the control group after the challenge phase, on the treated area with liquid paraffin.
In conclusion, the substance does not have to be classified in category 1 as a skin sensitiser, in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
Reference
On the challenge control sites (challenged at the other flank with liquid paraffin) one animal was observed with discrete to intense erythema at the 24 and 48 hours reading. This effect was fully reversible at the 72 hours reading.
groups |
Time (h) |
Concentrations |
Incidence
|
% of positive responses |
% of sensitized
|
|||
|
|
|
0 |
1 |
2 |
3 |
|
|
Control Group 1
|
24 |
100% |
10 |
0 |
0 |
0 |
0% |
|
48 |
100% |
10 |
0 |
0 |
0 |
0% |
|
|
72 |
100% |
10 |
0 |
0 |
0 |
0% |
|
|
24 |
0% |
10 |
0 |
0 |
0 |
0% |
|
|
48 |
0% |
10 |
0 |
0 |
0 |
0% |
|
|
72 |
0% |
10 |
0 |
0 |
0 |
0% |
|
|
Treated Group 2 |
24 |
100% |
20 |
0 |
0 |
0 |
0% |
0% |
48 |
100% |
20 |
0 |
0 |
0 |
0% |
0% |
|
72 |
100% |
20 |
0 |
0 |
0 |
0% |
0% |
|
24 |
0% |
19 |
0 |
0 |
1 |
5% |
0% |
|
48 |
0% |
19 |
1 |
0 |
0 |
5% |
0% |
|
72 |
0% |
20 |
0 |
0 |
0 |
0% |
0% |
Grading scale
0....... No visible change
1....... Discrete or patchy erythema
2....... Moderate and confluent erythema
3....... Intense erythema and swelling
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
The analogue Bis(2-ethylhexyl) azelate is not sensitizing to the skin (weight of evidence based on an ambiguous LLNA test and negative in vitro and Buehler tests). Uptake via the skin for this source substance is expected to be limited and both azelaic acid and ethylhexanol are not sensitizing. As the other hydrolysis products of Diesters of alcohols, C7-9-iso-, C8-rich, 2-ethylhexyl and nonanedioic acid also do show sensitizing properties and the toxicokinetic behaviour of the substance is very similar to that of Bis(2-ethylhexyl) azelate, no sensitization is expected for Diesters of alcohols, C7-9-iso-, C8-rich, 2-ethylhexyl and nonanedioic acid.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the information available, no classification for sensitization according to Regulation EC No 1272/2008 (CLP) for Diesters of alcohols, C7-9-iso-, C8-rich, 2-ethylhexyl and nonanedioic acid is considered necessary.
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.
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