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EC number: - | 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 Jan - 10 Feb 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- An in vivo study was conducted because in vitro/in chemico test methods described under Annex VII, 8.3.1 of Regulation (EC) No. 1907/2006 are not applicable, or the results obtained from those studies are not adequate for classification and risk assessment. For details, please refer to the document attached below.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted in 2010
- Deviations:
- yes
- Remarks:
- humidity in animal room out of range for one day
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Version / remarks:
- adopted in 2003
- Qualifier:
- according to guideline
- Guideline:
- other: EC No 640/2012, Part B
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 2,2-bis[(hexadecanoyloxy)methyl]propane-1,3-diyl dihexadecanoate
- Cas Number:
- 18641-58-2
- Molecular formula:
- C69H132O8
- IUPAC Name:
- 2,2-bis[(hexadecanoyloxy)methyl]propane-1,3-diyl dihexadecanoate
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Remarks:
- inbred
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Females nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: approx. 11 weeks
- Weight at study initiation: 20.5 – 26.9 g
- Housing: in groups up to 5/sex in polycarbonate cages (Makrolon MIII type, height 18 cm), with sterilised wooded fibers as bedding. For enrichment, paper and shelters were provided.
- Diet: pelleted rodent diet (SM R/M, Ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: municipal tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: Before the initiation of dosing, a health inspection was performed and any assigned animal considered unsuitable for use in the study were replaced by alternate animals obtained from the same shipment and maintained under the same environmental conditions.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 39 – 44
- Air changes (per hr): ≥ 10
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: 15 Jan - 08 Feb 2021
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Remarks:
- AcOO
- Concentration:
- Pre-test: 25% (w/w)
Main study: 5, 10 and 25% (w/w) - No. of animals per dose:
- 5 females
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: The vehicle was selected on the basis of maximizing the solubility based on trial preparations performed at the testing facility. At 50%, the formulation was too dry for application to the ears.
- Irritation: Only very slight irritation of the ears was observed.
- Systemic toxicity: There were no signs of systemic toxicity.
- Ear thickness measurements: No increase in ear thickness of 25% or more at a test item concentration of 25% (w/w) was noted from study Days 1 – 3 and 1 - 6 and thus, the test substance was not considered irritating at these concentrations.
- Erythema scores: At 25% (w/w) the animals showed very slight erythema (score 1) on both ears. The signs were observed on Days 2 and 3 and the animals were free from skin reactions thereafter. In addition, white test item remnants were present on the dorsal surface of the ears of both animals dosed at 25% between Days 1 and 3, which did not hamper scoring of the skin reactions.
MAIN STUDY
Based on the pre-screen test results, test substance concentrations of 5, 10 and 25% (w/w) were chosen for the main study.
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node assay. Cellular proliferation was determined by incorporation of 3H-methyl-thymidine.
- Criteria used to consider a positive response: The test item was considered positive in the LLNA if the incorporation of 3H-methyl-thymidine, indicated by stimulation index, was at least 3-fold when compared to control mice.
TREATMENT PREPARATION AND ADMINISTRATION:
The dorsal surface of both ears was topically treated with 25 µL/ear at concentrations of 5, 10 and 25% w/w. The animals were treated on each ear for 3 consecutive days (Induction Days 1, 2 and 3).
On study Day 6, each animal was injected via the tail vein with 0.25 mL of sterile phosphate buffered saline (PBS) containing 20 µCi of 3H-methyl thymidine. About 5 hours after injection, the animals were euthanized and the draining (auricular) lymph node of each ear was excised. The relative size of the nodes (as compared to normal) was estimated by visual examination and abnormalities of the nodes and surrounding area were recorded. The draining lymph nodes were pooled for each experimental group.
Following excision of the nodes, single cell suspensions of pooled lymph node cells (LNC) were prepared in PBS by gentle separation through stainless steel gauze. LNC were washed twice with an excess of PBS by centrifugation and exposed to 5% trichloroacetic acid (TCA) for DNA precipitation overnight in the refrigerator. Afterwards, the precipitates were re-suspended in TCA and transferred to scintillation fluid. Radioactivity measurements were performed using a Packard scintillation counter (2910TR) and the number of radioactive disintegrations per minute (DPM) was assessed.
CLINICAL SIGNS
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Post-dose observations were performed once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing). All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing.
BODY WEIGHT
Animals were weighed individually on Day 1 (pre-dose) and 6 (prior to necropsy) - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
- Positive control results:
- Reliability checks are performed regularly. A periodic positive control experiment using 5, 10 and 25% solutions of alpha-hexyl-cinnamaldehyde (v/v) in acetone:olive oil (4:1) was performed in Nov 2020. The SI values obtained were 2.1, 3.6 and 9.0 at 5, 10 and 25 %, demonstrating the validity of the test. An EC3 value of 8.0% was established, which fell into the acceptable range of 4.8 - 19.5%.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- 1.6
- Test group / Remarks:
- 5% formulation
- Key result
- Parameter:
- SI
- Value:
- 1.4
- Test group / Remarks:
- 10% formulation
- Key result
- Parameter:
- SI
- Value:
- 1.1
- Test group / Remarks:
- 25% formulation
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION:
The SI of the 5, 10 and 25% treatment group was 1.6, 1.4 and 1.1%, respectively.
EC3 CALCULATION:
The EC3 value could not be calculated, since all SI values were below the threshold value of 3.
CLINICAL OBSERVATIONS:
One animal died during the IV injection with 3H-methyl thymidine on Day 6, which was considered not test item related. In addition, no clinical signs of systemic toxicity were noted in any animal.
BODY WEIGHTS:
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.
SIGNS OF TOXICITY (including dermal irritation at the site of administration, if any, e.g. increased ear thickness):
No irritation was observed in any of the animals. White test item remnants were present on the dorsal surface of the ears of all animals dosed at 10% and 25% between Days 1 and 3, which did not hamper scoring of the skin reactions.
Any other information on results incl. tables
Table 2: Relative size of lymph nodes, radioactivity counts (DPM) and stimulation index (SI)
Test item formulation | Animal | Relative size auricular lymph nodes | DPM | SI | ||
left | right | DPM/animal | mean ± SEM | mean ± SEM | ||
0% | 1 | n | n | 81 | 193 ± 57 | 1.0 ± 0.3 |
2 | n | n | 206 | |||
3 | - | - | - | |||
4 | n | n | 140 | |||
5 | n | n | 345 | |||
5% | 6 | n | n | 400 | 306 ± 43 | 1.6 ± 0.2 |
7 | n | n | 301 | |||
8 | n | n | 378 | |||
9 | n | n | 152 | |||
10 | n | n | 298 | |||
10% | 11 | n | n | 469 | 276 ± 53 | 1.4 ± 0.3 |
12 | n | n | 267 | |||
13 | n | n | 239 | |||
14 | n | n | 259 | |||
15 | n | n | 146 | |||
25% | 16 | n | n | 327 | 214 ± 35 | 1.1 ± 0.2 |
17 | n | n | 185 | |||
18 | n | n | 144 | |||
19 | n | n | 263 | |||
20 | n | n | 153 | |||
DPM: disintegrations per minute; SEM: standard error of the mean; n: normal; -: animal died during IV injection with 3H-methyl thymidine on Day 6, not attributed to treatment with the test item |
Table 3: Body weights and skin reactions
Group | Test item (% w/w) | Animal | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | ||||||||
Body weight (g) | Erythemax | Erythemax | Erythemax | Erythemax | Erythemax | Erythemax | Body weight (g) | |||||||||
left | right | left | right | left | right | left | right | left | right | left | right | |||||
1 | 0 | 1 | 25.4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25.8 |
2 | 25.9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 26.0 | ||
3 | 26.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25.6 | ||
4 | 23.6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 24.3 | ||
5 | 22.6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 24.6 | ||
2 | 5 | 6 | 22.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 22.4 |
7 | 22.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 23.4 | ||
8 | 24.6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25.4 | ||
9 | 24.7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25.0 | ||
10 | 25.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 24.9 | ||
3 | 10* | 11 | 26.9 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 25.7 |
12 | 20.8 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 22.9 | ||
13 | 25.4 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 25.0 | ||
14 | 25.0 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 24.3 | ||
15 | 23.6 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 22.7 | ||
4 | 25# | 16 | 24.1 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 25.3 |
17 | 24.0 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 23.8 | ||
18 | 23.1 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 22.5 | ||
19 | 20.5 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 22.2 | ||
20 | 24.7 | 0f | 0f | 0f | 0f | 0f | 0f | 0 | 0 | 0 | 0 | 0 | 0 | 24.0 | ||
x: Grading erythema and eschar formation (Left = dorsal surface of left ear; right = dorsal surface of right ear) | ||||||||||||||||
*: Applied using a pipette with the tip cut off. | ||||||||||||||||
#: Applied using a spatula, instead of using a pipette | ||||||||||||||||
f: White staining of test item remnants on the dorsal surface of the ears did not hamper scoring for erythema. |
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The skin sensitisation potential of the test substance was assessed in a LLNA. Application of the test substance to mice ears at 5, 10 and 25% resulted in a calculated mean SI value of 1.6, 1.4 and 1.1%, respectively. The positive control demonstrated the validity and sensitivity of the test. Thus, the test substance is considered not sensitising according to Regulation (EC) No. 1272/2008.
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