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EC number: 627-025-5 | CAS number: 101541-04-2
- 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:
- 2012-07-18 to 2012-08-09
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- yes
- Remarks:
- There were occasional procedural deviations that were minor and did not impact the integrity or outcome of the study
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- (2S,3S)-2-(hexadecanoylamino)-3-methylpentanoic acid
- Cas Number:
- 54617-29-7
- Molecular formula:
- C22H43NO3
- IUPAC Name:
- (2S,3S)-2-(hexadecanoylamino)-3-methylpentanoic acid
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): L-Isoleucine, N-(1-oxohexadecyl)
- Substance type: Lipoamino acid
- Physical state: White powder with granule
- Purity test date: 2011-06-02
- Purity: 99% dry extract
- Lot/batch No.: 1110400022
- Retest date of the lot/batch: 2014-04-13
- Storage condition of test material: room temperature
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Jackson Laboratory, (Bar Harbor, Maine, USA, 04609)
- Age at study initiation: from 10 to 11 weeks
- Weight at study initiation: from 20 to 26 g
- Housing: Animals were group housed in stainless steel rodent cages equipped with an automatic watering system. In the main test, on Day 6, before the 3H-TdR injections, the animals were individually housed in solid bottom cages. Following group assignment, all cages were clearly labeled with a color-coded cage card indicating at least the following: study number and animal number (including gender and group number).
- Diet/ Water(e.g. ad libitum):
A standard certified commercial chow (Harlan Teklad Certified Global Rodent Diet #2018C) was provided to the animals ad libitum. Concentrations of the contaminants (e.g., heavy metals, aflatoxin, organophosphate and chlorinated hydrocarbons) were routinely measured by the manufacturers (batch certificates on file at CiToxLAB North America).
Municipal tap water (which was exposed to ultraviolet light and purified by reverse osmosis) was provided to the animals ad libitum, via an automatic watering system. Periodic analyses of the municipal tap water (purified water) were performed by a CiToxLAB North America designated facility and the results are retained on file at CiToxLAB North America.
- Acclimation period: 7 to 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3C
- Humidity (%): 50 ± 20%;
- Air changes (per hr): 10 – 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 0.5% ; 1% ; 2.5% ; 5% ; 10%
- No. of animals per dose:
- 4
- Details on study design:
- RANGE FINDING TESTS:
Dose concentrations for the dose selection phase (preliminary assay) and selected solvent (N, N-dimethylformamide (DMF)) were gave by the sponsor, and were confirmed within the solubility assay performed at CiToxLAB North America.
Main Test Phase:
The maximum concentration tested in the main test was selected according to the criteria specified in the OECD Guidelines and on the basis of the data that were obtained in the preliminary test:
• The vehicle was selected on the basis of producing a homogeneous preparation suitable for application of the test item, based on data given by the sponsor using N, N-dimethylformamide (DMF) as a solvent and as confirmed within the solubility assay performed at CiToxLAB North America.
• The concentrations were selected from the concentration series 25%, 10%, 5%, 2.5%, 1.0%, 0.5%, etc.
The maximum concentration of the test item was defined on the basis of the results of the preliminary assay and selected to avoid overt systemic toxicity and excessive local skin irritation; the latter being defined by a > 25% increase of the ear thickness
- Lymph node proliferation response:
Lymph node cell proliferative response was measured as described by Kimber and Dearman.
On Day 6 of the main test, all animals of all groups received a single intravenous injection (animal No. 4502 punctured twice) of an adjusted volume of 230 µL (based on the radioactivity concentration analysis results (87.73 µCi/g)) of NaCl 0.9% containing a dose of 20 µCi of 3H-TdR (specific activity of 20 Ci/mmol) via the tail vein.
Approximately 5 hours post-3H-TdR administration, the main test animals were euthanized by an intraperitoneal injection of pentobarbital sodium followed by a cervical dislocation and the auricular lymph nodes (ALN) were excised bilaterally. The lymph nodes were pooled for each experimental group. The number of ALN sampled for each group was documented. A single cell suspension of ALNCs was prepared by mechanical disaggregation in Petri dishes using the plunger of a syringe. The carcasses were then appropriately disposed of without any further examination.
MAIN STUDY
The test item would be regarded as a skin sensitizer when the SI for a dose group is >= 3 together with consideration of a dose-response relationship. Other relevant criterias such as radioactivity levels, chemical toxicity, and ear thickness was also taken into account to evaluate the data.
Every attempt was made to determined the EC3 value (theoretical concentration resulting in a SI value of 3) as requested by the Ministry. Given sufficient data, the EC3 would be determined by linear interpolation of points on the dose-response curve, immediately above and below the 3-fold threshold. The equation to be used for calculation of EC3 is:
EC3 = c + [(3 – d)/(b – d)] x (a – c)
Where a = the lowest concentration giving stimulation index > 3; b = the actual stimulation index caused by a; c = the highest concentration failing to produce a stimulation index of 3; and d = the actual stimulation index caused by c.
Categorization of contact allergens on the basis of relative skin sensitization potency, using EC3 values derived from the LLNA are listed in the table below.
TREATMENT PREPARATION AND ADMINISTRATION:
- Prior to the in-life phase, solubility assays were performed by CiToxLAB North America to verify solubility of the test item at the concentration of 25% (w/v) in N, N¬-dimethylformamide (DMF). As a solution to the naked eye at 25% was obtained, the test item was not tested at lower concentrations in the same vehicle.
- The test item was administered as a solution in the vehicle. As required, the test item was grounded to a fine powder and then mixed by vortex or under magnetic agitation, with the required quantity of vehicle. The test item concentrations were expressed in % (w/v).
-For both phases, on Days 1, 2, and 3, a dose-volume of 25 µL of the positive control, negative/vehicle control, or test item dosage formulations was applied to the dorsal surface of both ears (one concentration/ear in the Preliminary Phase, and one concentration/animal in the Main Test Phase), using an adjustable pipette fitted with a plastic tip.
In order to avoid licking and to ensure an optimized application of the test materials, the animals were placed under light isoflurane ((2-chloro-2-(difluoromethoxy)-1, 1, 1-trifluoro-ethane) anesthesia during the administration.
No massage was performed but the tip was used to spread the preparation over the application site. No rinsing was performed. On Day 2 of the preliminary test, a small leakage from right ear was observed on animal No. 2502. This was considered without impact on the study as the results for this animal were consistent and dosing is performed for 3 days on the same ears and as such would not significantly affect the results.
The dosing formulations were stirred continuously throughout the dosing procedure. Any dosing formulations remaining after each daily dosing were discarded. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
- Positive control results:
- The threshold positive value of 3 for the SI was reached in the positive control group
(SI = 7.78). The experiment was therefore considered valid.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: see Remark
- Remarks:
- Group SI Negative control (AOO) 1 Negative control (DMF) 1 Positive control (HCA) 25% 7.78 Test item 0.5% 0.42 Test item 1% 0.45 Test item 2.5% 0.84 Test item 5% 1.96 Test item 10% 1.80
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: see Remark
- Remarks:
- Group nbre of node DPM/group DPM/node Negative control (AOO) 8 221.5 27.69 Negative control (DMF) 8 271.6 33.95 Positive control (HCA) 25% 8 1722.6 215.33 Test item 0.5% 8 113.5 14.19 Test item 1% 8 121.8 15.23 Test item 2.5% 8 228.3 28.54 Test item 5% 8 532.2 66.53 Test item 10% 8 489.1 61.14
- Parameter:
- SI
- Value:
- ca. 0.42
- Test group / Remarks:
- 4 female / concentration 0.5 %
- Parameter:
- SI
- Value:
- ca. 0.45
- Test group / Remarks:
- 4 female / concentration 1 %
- Parameter:
- SI
- Value:
- ca. 0.84
- Test group / Remarks:
- 4 female / concentration 2.5 %
- Parameter:
- SI
- Value:
- ca. 1.96
- Test group / Remarks:
- 4 female / concentration 5 %
- Parameter:
- SI
- Value:
- ca. 1.8
- Test group / Remarks:
- 4 female / concentration 10 %
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Migrated information
- Conclusions:
- Under the experimental conditions of this study, the test item, L-Isoleucine, N-(1-oxohexadecyl), gave a negative results in the murine Local Lymph Node Assay, indicative of the absence of skin sensitization properties.
- Executive summary:
The objective of this study was to evaluate the potential of the test item, L-Isoleucine, N-(1-oxohexadecyl),to induce contact hypersensitivity, using the murine Local Lymph Node Assay (LLNA).
To assess the irritant potential of the test item (through ear thickness measurement), a preliminary test was first performed in order to define the test item concentrations to be used in the main test. Two groups of 2 female mice received the test item, L-Isoleucine, N-(1-oxohexadecyl) dissolved inN,N-dimethylformamide (DMF), by topical route to the dorsal surface of both ears (one concentration per ear) on Days 1, 2 and 3 at concentrations of 25, 10, 5, or 2.5 % with a dose-volume of 25µL. From Day 1 to Day 3 and then on Day 6, the thickness of both ears of each animal was measured and the local reactions recorded. On completion of the observation period, the animals wereeuthanized per the standard operating procedures and the carcasses appropriately disposed of without post-mortem investigations.
Based on the preliminary test results, the test, negative, and positive control items in the main test, were administered daily from Day 1 to Day 3 inclusive as shown below:
Group
Number of
animals
Administration
Concentration
(%)
3
4 females
Negative Control (AOO, 4:1 (v/v))
0
4
4 females
Negative Control (DMF)
0
5
4 females
Positive Control Itema
25% of HCA
6
4 females
Low Dose
0.5b
7
4 females
Low-mid Dose
1.0b
8
4 females
Mid Dose
2.5b
9
4 females
Mid-high Dose
5.0b
10
4 females
High Dose
10.0b
a:α-hexyl cinnamaldehyde (HCA) in Acetone:Olive Oil, 4:1 v/v (AOO).
b: Was chosen according to the results obtained in the preliminary test.
DMF:N, N-dimethylformamide
Following the end of the 3-day administration period, main phase animals were euthanized on Day 6 and ear thickness measurements and LLNA was performed.
There were no L-Isoleucine, N-(1-oxohexadecyl)-related mortalities or body weight changes observed.
The SI of the positive control was >3; this experiment was therefore considered valid
A summary of the test and positive control items results are presented in the following table
Main Test Phase Results
Treatment
Concentration
(%)
Irritation level
Stimulation Index
(SI)
Test item (in DMF)
0.5
I
0.42
Test item (in DMF)
1.0
I
0.45
Test item (in DMF)
2.5
II
0.84
Test item (in DMF)
5.0
II
1.96
Test item (in DMF)
10.0
II
1.80
HCA (in AOO)
25
I
7.78
Negative control (AOO)
-
I
1.00
Negative control (DMF)
-
I
1.00
No notable lymphoproliferation was noted with the test item at any tested concentrations (0.5 to 10%). No EC3value could be determined in the absence of a SI ≥ 3. Under the experimental conditions of this study, the test item, L-Isoleucine, N-(1-oxohexadecyl), gave a negative results in the murine Local Lymph Node Assay, indicative of the absence of skin sensitization properties.
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