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EC number: 218-465-5 | CAS number: 2157-01-9
- 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:
- Experiment start 06 March, experiment completion April 11, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- OECD Guidelines for Testing of Chemicals No. 429 “Skin Sensitisation: Local Lymph Node Assay”(adopted 22 July 2010)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Octyl methacrylate
- EC Number:
- 218-465-5
- EC Name:
- Octyl methacrylate
- Cas Number:
- 2157-01-9
- Molecular formula:
- C12H22O2
- IUPAC Name:
- octyl 2-methylprop-2-enoate
- Test material form:
- liquid
- Details on test material:
- - Analytical purity: 98.49 %
- Batch: 1324855
1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- Species and strain: CBA/J mice
Source: Animal Breeding Facility, Jai Research Foundation, India
Number of animals: 8 animals (2 mice/group) for preliminary assay, and 25 (5 mice/group) for main study
Sex: Female, nulliparous, non pregnant
Age of animals at starting: 10-11 weeks old at the initiation of treatment
Body weight range at starting: 20.3 – 25.6 grams
Acclimatization time: 6 days
Husbandry
Animal health: Only healthy animals were used for the study. Health status was certified by the veterinarian.
Caging : Solid floor polypropylene mice cages (size: approx. 290 mm x 220 mm x 140 mm). Each cage is fitted with a top grill having provision for keeping rodent pellet feed and water bottles. The bottom of the cages is layered with clean sterilized rice husk as the bedding material. Animals were group-housed during acclimatisation. On the days of test item application (days 0, 1 and 2), the animals were housed in individual cages. From day 3, the animals were group housed 5 mice/cage. On day 5, animals were housed in metabolic cages.
Water Bottle : Each cage was supplied with a polypropylene water bottle (capacity 300 mL) with a stainless steel nozzle.
Room Sanitation : Daily: 1. Rack was cleaned with cloth, 2. Floor of experimental procedure room was swept, 3. All work tops and the floor were mopped with a disinfectant solution.
Enrichment Material : Tunnel
Light: 12 hours daily, from 6:00 a.m. to 6:00 p.m.
Temperature: 20 - 23°C
Relative humidity: 58 - 67 %
Ventilation: minimum 15 air exchanges/hour
The temperature and relative humidity were recorded twice every day during the acclimatisation and experimental phases.
Food and feeding
- Diet: Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, USA, ad libitum
- Water: UV sterilised water (Reverse Osmosis water filtration system) ad libitum
Identification and randomisation
The animals were identified with appropriate labels attached to the cages indicating the study number, test item code, group number, sex, dose, cage number and animal number. Animals (except preliminary assays animals) were tattooed on paw [Animal No 1 marked with small dot on right paw (forelimb), Animal No 2 on the right and left paws (forelimb), Animal No 3 on the right and left paws (forelimb) and right paw (hindlimb), Animal No 4 on the right and left paws (forelimb and hindlimb) and Animal N° 5 had no marking] after randomisation.
After acclimatisation animals were randomised into five groups using in-house developed, validated computer software.
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- The highest achievable concentration based on the regulatory requirements of the OECD guideline and the physical characteristics of the test item was 100 % (undiluted). The formulations at 50 and 25 % (w/v) in AOO were also suitable for treatment in this study.
- No. of animals per dose:
- 8 animals (2 mice/group) for preliminary assay, and 25 (5 mice/group) for main study dose
- Details on study design:
- Formulation
The test item was mixed with vehicle to obtain the desired dose concentrations. Fresh dose solutions were prepared prior to application on days 0, 1 and 2. Required quantity of the test item was mixed with vehicle to get the desired concentration. The concentrations of the dose solutions were not verified analytically.
ADMINISTRATION OF THE TEST ITEM
Dose Selection and Justification of Dose Selection
In the preliminary assay, less than 25% ear thickness was observed at 10%, 25%, 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% concentration.
No erythema was observed at 10%, 25% 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% concentration. Therefore, dose concentrations of 25% and 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% n-oct
yl methacrylate were evaluated in the main study of LLNA.
Topical application
Three groups (G2 to G4) were treated topically for three consecutive days (days 0, 1 and 2) on the dorsal surface of both ears (25 µL/ear) using a calibrated micropipette with n-octyl methacrylate at concentrations of 25% and 50% in acetone:olive oil (4:1 v/v) and 100% (undiluted) n-octyl methacrylate, respectively. Mice from vehicle control group (G1) and positive control group (G5) were handled in the same manner but received 25 µL/ear of vehicle (acetone:olive oil (4:1 v/v)) and 25% a-Hexylcinnamaldehyde (v/v) in vehicle (acetone:olive oil (4:1 v/v)), respectively.
PROLIFERATION ASSAY
Injection of Tritiated Thymidine (3HTdR)
On day 5, all mice from the vehicle control, positive control and all the treatment groups were injected with 250 µL of sterile phosphate buffered saline (PBS) containing approximately 20 ± 1 µCi (740 KBq) of ³H-methyl thymidine via the tail vein.
Removal and Preparation of Draining Auricular Lymph Nodes
On day 5, 5 hours post-administration of ³H-methyl thymidine, all mice from the vehicle control, positive control and all the treatment groups were euthanised by CO2 asphyxiation. The draining auricular lymph nodes from each mouse were excised and combined in phosphate buffered saline.
Preparation of Single Cell Suspension of Lymph Node Cells
The draining auricular lymph nodes of individual mouse were collected in separate petridishes containing phosphate buffered saline (PBS). A single cell suspension of lymph node cells was prepared by gentle mechanical disaggregation through 200 to 210 µm-mesh stainless steel gauze with the plunger of the syringe and collected in a petridish. The gauze was washed with PBS into the petridish and a single cell suspension was transferred into a 15 mL graduated centrifuge tube. The single cell suspension was finally made up to 10 mL with PBS used to rinse the petridish. The cell suspension was centrifuged approximately at 190 to 200 g for 10 minutes in a centrifuge at 4 °C.
After centrifugation, the supernatant was removed by aspiration using a micropipette leaving 1 mL of supernatant above each pellet. Each pellet was gently agitated before making up to 10 mL with PBS, this procedure was repeated twice. After the final wash, the supernatant was removed leaving a minimal volume (approximate 0.5 mL) of supernatant above each pellet.
Each pellet was agitated before re-suspending with 3 mL of 5% trichloroacetic acid (TCA) and kept for precipitation of macromolecules in the refrigerator for approximately 18 hours. After incubation with 5% TCA at 4 ± 1 °C, each precipitate was recovered by centrifugation (190 to 200 g) for 10 minutes and the supernatant was removed.
The precipitate was re-suspended in 1 mL of 5% TCA. Each precipitate was transferred to a scintillation vial with 10 mL of scintillation fluid (Hionic flour) and thoroughly mixed. After minimum period of 30 minutes, the vials were loaded into a β–scintillation counter for measuring the ³H-methyl thymidine incorporation. Background ³H-methyl thymidine level was measured into 1 mL aliquots of 5% TCA.
Determination of Incorporated ³HTdR
Incorporation of ³H-methyl thymidine was measured by β-scintillation counting as disintegrations per minute (DPM) for each mouse and expressed as DPM/mouse. The total radioactivity of each sample was counted using LSA (Liquid Scintillation Analyser) after 30 minutes of mixing with scintillation fluid and required quench corrections were made.
The quench curve was established using extended quench standards (PerkinElmer) of DPM β source. Computer constructed quench curve was derived from the above commercially available series of scaled standards which automatically converts Counts Per Minute (CPM) to DPM.
OBSERVATIONS
Clinical Observations
Individual animals were observed carefully for clinical signs and local irritation at the site of application and systemic toxicity. All the observations were systematically recorded for individual mice. Local irritation responses were made as per criteria given below (OECD 429, 2010; Section 22):
Observation Score
-----------------------------------------------------------------------------------------------------------------------
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema) 4
Measurement of Body Weight
Body weights of individual mouse were recorded on the first day of dosing (day 0) and prior to administration of ³H-methyl thymidine (day 5). Group mean body weights were calculated. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- In addition to an assessment of the magnitude of the SI, statistical analysis was carried out for the assessment of the dose response relationship and pair-wise comparison made between the treatment and the solvent/vehicle control group. All the parameters characterised by continuous data such as body weight and radioactive disintegrations per minute (DPM) were subjected to Bartlett’s test to meet the homogeneity of variance before conducting Analysis of Variance (ANOVA). To compare vehicle and positive control data, Student’s t-test was performed to calculate significance.
Results and discussion
- Positive control results:
- The result of the positive control substance a-Hexylcinnamaldehyde (HCA) dissolved in the same vehicle was used to demonstrate the appropriate performance of the assay. The positive control substance was examined at a concentration of 25% in the relevant vehicle (AOO) using CBA/J mice.
No mortality, cutaneous reactions or signs of toxicity were observed for the positive control substance in the study. A lymphoproliferative response in line with historic positive control data (stimulation index value of 5.83) was noted for HCA in the main experiment. This value was considered to confirm the appropriate performance of the assay.
Furthermore, the DPN values observed for the vehicle and positive control substance in this experiment were within the historical control range. Each treated and control group included 5 animals.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 2.55
- Test group / Remarks:
- 25 %
- Parameter:
- SI
- Value:
- 4.2
- Test group / Remarks:
- 50%
- Parameter:
- SI
- Value:
- 4.98
- Test group / Remarks:
- 100%
- Key result
- Parameter:
- EC3
- Remarks:
- %
- Value:
- 31.82
- Cellular proliferation data / Observations:
- CLINICAL OBSERVATION
No mortality or signs of systemic toxicity were observed during the study. There were no indications of any irritancy at the site of application. In all mice treated with 25% HCA, a local reaction consisting of erythema (score of 1) was observed from days 2 to 4 (5/5 mouse).
BODY WEIGHT MEASUREMENT
No treatment related effects were observed on the body weight changes of experimental animals.
PROLIFERATION ASSAY
Proliferative responses in the draining lymph nodes were monitored by measuring the incorporation of 3H-methyl thymidine. These analyses revealed group mean DPM values of 1983.20, 2861.80, 4342.00 and 3333.20 for the vehicle control (acetone:olive oil (4:1 v/v)), 25%, 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% n-hexyl methacrylate, respectively. The DPM value for positive control (25% alpha-Hexylcinnamaldehyde) was found to be 9637.40.
A statistically significant increase in mean DPM was observed in 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% n-octyl methacrylate and 25% (v/v) HCA when compared to vehicle control group values.
INTERPRETATION OF OBSERVATIONS
The test item was a liquid, which was formulated in AOO. Since there were no confounding effects of treatment related irritation or systemic toxicity at the applied concentrations, the proliferation values obtained are considered to reflect the real potential of the test item to cause lymphoproliferation in the Local Lymph Node Assay.
A Stimulation Index (SI) of three or more (SI value of treated group over the control) indicates potential to cause skin sensitisation.
The SI obtained for n-octyl methacrylate at 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% concentration showed a greater than threefold increase compared to the vehicle control value with an EC3 value found to be 31.82%. Therefore, n-octyl methacrylate demonstrates weak dermal sensitisation potential in the local lymph node assay.
The SI of 5.83 obtained for the concurrent positive control, alpha-Hexylcinnamaldehyde, showed greater than a three-fold increase over the control value indicating a positive response in agreement with the historical control for this known weak sensitiser. This confirmed the reliability of this test procedure.
Any other information on results incl. tables
Skin Sensitisation Study of n-Octyl Methacrylate by Local Lymph Node Assay in Mice
Individual Body Weights for all Animals with Group Means
Animal Number |
Test Group Name |
Initial (Day 0) Body Weight (g) |
Terminal ( Day 5)Body Weight*(g) |
Change#(%) |
|
G1 |
1 2 3 4 5 |
Negative (vehicle) control AOO
Mean |
25.6 23.0 22.3 21.5 20.8 22.6 |
26.3 24.0 23.0 22.2 22.0 23.5 |
2.7 4.3 3.1 3.3 5.8 3.8 |
G2 |
6 7 8 9 10 |
n-octyl methacrylate 25% (v/v) in AOO
Mean |
25.6 23.5 22.7 21.9 20.6 22.9 |
26.3 24.0 23.4 22.1 21.0 23.4 |
2.7 2.1 3.1 0.9 1.9 2.1 |
G3 |
11 12 13 14 15 |
n-octyl methacrylate 50% (v/v) in AOO
Mean |
25.0 23.4 22.4 21.0 20.3 22.4 |
25.3 23.9 23.0 21.5 20.8 22.9 |
1.2 2.1 2.7 2.4 2.5 2.2 |
G4 |
16 17 18 19 20 |
n-octyl methacrylate 100% (undiluted)
Mean |
25.4 23.0 22.3 22.0 21.0 22.7 |
26.2 24.0 22.8 22.7 22.0 23.5 |
3.1 4.3 2.2 3.2 4.8 3.5 |
G5 |
21 22 23 24 25 |
Positive control 25 (v/v) % HCA in AOO
Mean |
23.9 23.0 22.0 21.5 20.9 22.3 |
24.5 23.6 23.0 22.1 21.5 22.9 |
2.5 2.6 4.5 2.8 2.9 3.1 |
*: Terminal body weights were measured on Day 5.
#: = (Terminal Body Weight – Initial Body Weight) / Initial Body Weight x 100
DPM, DPN and Stimulation Index Values for all Groups
Test Group Name |
Identity No |
Measured Total DPM |
DPM* |
Group DPM |
Standard Deviation |
SI |
G1 Negative (0% vehicle) control (AOO) |
1 2 3 4 5 |
1218 644 986 1425 879 |
1169 595 937 1376 830 |
981.40 |
302.12 |
1.0 |
G2 n-octyl methacrylate 25% (v/v) in AOO |
6 7 8 9 10 |
2293 2187 3419 2500 2378 |
2244 2138 3370 2451 2329 |
2506.40 |
496.21 |
2.55 |
G3 n-octyl methacrylate 50% (v/v) in AOO |
11 12 13 14 15 |
5397 2705 3228 4921 4583 |
5348 2656 3179 4872 4534 |
4117.80* |
1148.22 |
4.20 |
G4 n.-octyl methacrylate 100% (undiluted) |
16 17 18 19 20 |
4812 3884 4634 7091 4264 |
7463 3835 4585 7042 4215 |
4888.00* |
1255.87 |
4.98 |
G5 Positive control (25% (v/v) HCA in AOO) |
21 22 23 24 25 |
4780 6927 5833 6687 4629 |
4731 6878 5784 6638 4580 |
5722.20* |
1056.58 |
5.83 |
Notes: DPM = Disintegration per minute, Measured Background DPM of 5% TCA = 14,
Measured DPM= Value measured by Liquid Scintillation Analyser,
DPM* = Measured DPM (individual animal) - Background DPM,
HCA = α-Hexylcinnamaldehyde,Vehicle = Acetone : Olive oil (4:1 v/v)
Stimulation Index= mean DPM of test group divided by mean DPM of solvent/vehicle control group
* = significantly higher than control (p ≤0.01)
Sex: Dermal irritation Scores Sex: Female
Group N° |
Dose Concentration (%) |
Mouse N° |
Erythema scores on Day |
|||||
0 |
1 |
2 |
3 |
4 |
5 |
|||
G1 |
0% (Vehicle control) |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
||
3 |
0 |
0 |
0 |
0 |
0 |
0 |
||
4 |
0 |
0 |
0 |
0 |
0 |
0 |
||
5 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G2 |
25% (v/v) n-Octyl Methacrylate |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
||
8 |
0 |
0 |
0 |
0 |
0 |
0 |
||
9 |
0 |
0 |
0 |
0 |
0 |
0 |
||
10 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G3 |
50% (v/v) n-Octyl Methacrylate |
11 |
0 |
0 |
0 |
0 |
0 |
0 |
12 |
0 |
0 |
0 |
0 |
0 |
0 |
||
13 |
0 |
0 |
0 |
0 |
0 |
0 |
||
14 |
0 |
0 |
0 |
0 |
0 |
0 |
||
15 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G4 |
100% n-Octyl Methacrylate (undiluted) |
16 |
0 |
0 |
0 |
0 |
0 |
0 |
17 |
0 |
0 |
0 |
0 |
0 |
0 |
||
18 |
0 |
0 |
0 |
0 |
0 |
0 |
||
19 |
0 |
0 |
0 |
0 |
0 |
0 |
||
20 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G5 |
25% (v/v) HCA |
21 |
0 |
0 |
1 |
1 |
1 |
0 |
22 |
0 |
0 |
1 |
1 |
1 |
0 |
||
23 |
0 |
0 |
1 |
1 |
1 |
0 |
||
24 |
0 |
0 |
1 |
1 |
1 |
0 |
||
25 |
0 |
0 |
1 |
1 |
1 |
0 |
Key: 0 = No erythema, 1 = Very slight erythema (barely perceptible), HCA = α-Hexylcinnamaldehyde, Vehicle = Acetone:Olive oil (4:1 v/v)
Clinical Observations of Individual Mouse other than Irritation Response
Sex: Female
Group N° |
Dose Concentration (%) |
Mouse N° |
Clinical Observation on Day |
|||||
0 |
1 |
2 |
3 |
4 |
5 |
|||
G1 |
0% (Vehicle control) |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
||
3 |
1 |
1 |
1 |
1 |
1 |
1 |
||
4 |
1 |
1 |
1 |
1 |
1 |
1 |
||
5 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G2 |
25% (v/v) n-Octyl Methacrylate |
6 |
1 |
1 |
1 |
1 |
1 |
1 |
7 |
1 |
1 |
1 |
1 |
1 |
1 |
||
8 |
1 |
1 |
1 |
1 |
1 |
1 |
||
9 |
1 |
1 |
1 |
1 |
1 |
1 |
||
10 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G3 |
50% (v/v) n-Octyl Methacrylate |
11 |
1 |
1 |
1 |
1 |
1 |
1 |
12 |
1 |
1 |
1 |
1 |
1 |
1 |
||
13 |
1 |
1 |
1 |
1 |
1 |
1 |
||
14 |
1 |
1 |
1 |
1 |
1 |
1 |
||
15 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G4 |
100% n-Octyl Methacrylate(undiluted) |
16 |
1 |
1 |
1 |
1 |
1 |
1 |
17 |
1 |
1 |
1 |
1 |
1 |
1 |
||
18 |
1 |
1 |
1 |
1 |
1 |
1 |
||
19 |
1 |
1 |
1 |
1 |
1 |
1 |
||
20 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G5 |
25% (v/v) HCA |
21 |
1 |
1 |
1 |
1 |
1 |
1 |
22 |
1 |
1 |
1 |
1 |
1 |
1 |
||
23 |
1 |
1 |
1 |
1 |
1 |
1 |
||
24 |
1 |
1 |
1 |
1 |
1 |
1 |
||
25 |
1 |
1 |
1 |
1 |
1 |
1 |
Key: HCA = α-Hexylcinnamaldehyde, Vehicle = Acetone:Olive oil (4:1 v/v)
Clinical Sign: 1 = Normal
Results of Preliminary Assay
Dermal Irritation Scores Sex: Female
Group N° |
Dose Concentration (%) |
Mouse N° |
Erythema on Days |
|||||
0 |
1 |
2 |
3 |
4 |
5 |
|||
G1 |
10% (v/v) n-Octyl Methacrylate |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G2 |
25% (v/v) n-Octyl Methacrylate |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
4 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G3 |
50% (v/v) n-Octyl Methacrylate |
5 |
0 |
0 |
0 |
0 |
0 |
0 |
6 |
0 |
0 |
0 |
0 |
0 |
0 |
||
G4 |
100% n-Octyl Methacrylate (undiluted) |
7 |
0 |
0 |
0 |
0 |
0 |
0 |
8 |
0 |
0 |
0 |
0 |
0 |
0 |
Note: 0 = No erythema, Vehicle = Acetone:Olive oil (4:1 v/v)
Group Mean Body Weight
Group N° |
Dose Concentration (%) |
N° of Mice Used |
Mean Body Weight (g) |
|
Day 0 |
Day 5 |
|||
G1 |
10% (v/v) n-Octyl Methacrylate |
2 |
22.2 ± 0.4 |
22.5 ± 1.0 |
G2 |
25% (v/v) n-Octyl Methacrylate |
2 |
24.1 ± 1.8 |
24.8 ± 1.6 |
G3 |
50% (v/v) n-Octyl Methacrylate |
2 |
22.2 ± 0.4 |
22.6 ± 0.3 |
G4 |
100% n-Octyl Methacrylate (undiluted) |
2 |
24.0 ± 1.0 |
25.0 ± 0.6 |
Note: Vehicle = Acetone : Olive oil (4:1 v/v)
Summary of Ear Thickness
Group N° |
Dose Concentration (%) |
Ear Thickness (mm) on Day (Mean± SD) |
|||||
0 |
2 |
5 |
|||||
Left |
Right |
Left |
Right |
Left |
Right |
||
G1 |
10% (v/v) n-Octyl Methacrylate |
0.240 ± 0.016 |
0.236 ± 0.018 |
0.248 ± 0.013 |
0.243 ± 0.018 |
0.256 ± 0.017 |
0.250 ± 0.020 |
G2 |
25% (v/v) n-Octyl Methacrylate |
0.243 ± 0.001 |
0.237 ± 0.004 |
0.254 ± 0.000 |
0.250 ± 0.003 |
0.264 ± 0.002 |
0.259 ± 0.001 |
G3 |
50% (v/v) n-Octyl Methacrylate |
0.252 ± 0.004 |
0.239 ± 0.010 |
0.276 ± 0.0002 |
0.267 ± 0.008 |
0.286 ± 0.003 |
0.275 ± 0.010 |
G4 |
100% n-Octyl Methacrylate(undiluted) |
0.252 ± 0.005 |
0.245 ± 0.007 |
0.294 ± 0.007 |
0.287 ± 0.008 |
0.307 ± 0.007 |
0.303 ± 0.010 |
Summary of Ear Thickness Percent Change
Group N° |
Dose Concentration (%) |
N° of Mice Used |
Mean Ear Thickness (percent change)(Mean± SD) |
|||
Left Ear Thickness (% Change) |
Right Ear Thickness (% Change) |
|||||
Day 2 |
Day 5 |
Day 2 |
Day 5 |
|||
G1 |
10% (v/v) n-Octyl Methacrylate |
2 |
3.379 ± 1.398 |
6.662 ± 0.158 |
2.775 ± 0.515 |
5.927 ± 0.137 |
G2 |
25% (v/v) n-Octyl Methacrylate |
2 |
4.743 ± 0.305 |
8.662 ± 1.191 |
5.492 ± 0.695 |
9.087 ± 1.654 |
G3 |
50% (v/v) n-Octyl Methacrylate |
2 |
9.334 ± 0.999 |
13.449 ± 0.788 |
11.738 ± 1.078 |
15.076 ± 0.624 |
G4 |
100% n-Octyl Methacrylate (undiluted) |
2 |
16.894 ± 0.511 |
22.064 ± 0.409 |
17.142 ± 0.083 |
23.667 ± 0.472 |
Note: Vehicle = Acetone : Olive oil (4:1 v/v)
Individual Animal Ear Thickness Measurement (mm)
Group N° |
Dose Concentration (%) |
Mouse N° |
Day 0 |
Day 2 |
Day 5 |
|||
Left |
Right |
Left |
Right |
Left |
Right |
|||
G1 |
10% (v/v) n-Octyl Methacrylate |
1 |
0.229 |
0.223 |
0.239 |
0.230 |
0.244 |
0.236 |
2 |
0.251 |
0.249 |
0.257 |
0.255 |
0.268 |
0.264 |
||
G2 |
25% (v/v) n-Octyl Methacrylate |
3 |
0.243 |
0.240 |
0.254 |
0.252 |
0.262 |
0.259 |
4 |
0.242 |
0.234 |
0.254 |
0.248 |
0.265 |
0.258 |
||
G3 |
50% (v/v) n-Octyl Methacrylate |
5 |
0.255 |
0.246 |
0.277 |
0.273 |
0.288 |
0.282 |
6 |
0.249 |
0.232 |
0.274 |
0.261 |
0.284 |
0.268 |
||
G4 |
100% n-Octyl Methacrylate(undiluted) |
7 |
0.255 |
0.250 |
0.299 |
0.293 |
0.312 |
0.310 |
8 |
0.248 |
0.240 |
0.289 |
0.281 |
0.302 |
0.296 |
Note: Vehicle = Acetone : Olive oil (4:1 v/v)
Clinical Observations of Individual Mouse other than Irritation Response
Group N° |
Dose Concentration (%) |
Mouse N° |
Clinical Observation on Day |
|||||
0 |
1 |
2 |
3 |
4 |
5 |
|||
G1 |
10% (v/v) n-Octyl Methacrylate |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G2 |
25% (v/v) n-Octyl Methacrylate |
3 |
1 |
1 |
1 |
1 |
1 |
1 |
4 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G3 |
50% (v/v) n-Octyl Methacrylate |
5 |
1 |
1 |
1 |
1 |
1 |
1 |
6 |
1 |
1 |
1 |
1 |
1 |
1 |
||
G4 |
100% n-Octyl Methacrylate(undiluted) |
7 |
1 |
1 |
1 |
1 |
1 |
1 |
8 |
1 |
1 |
1 |
1 |
1 |
1 |
Clinical Sign: 1 = Normal
Key: Vehicle = Acetone:Olive oil (4:1 v/v)
Applicant's summary and conclusion
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- In conclusion, under the conditions of the present assay, n-Octyl methacrylate, tested in a suitable vehicle, indicating weak skin sensitisation potential in the Local Lymph Node Assay. Based on this study result, n-octyl methacrylate is a dermal sensitiser.
Based on the results of this study, an indication of the classification for n-octyl methacrylate is as follows:
Globally Harmonized System of Classification and Labeling of Chemicals (GHS 2017): Classified as a weak skin sensitiser, Cat 1B - Executive summary:
The aim of the study was to determine the skin sensitisation potential of n-octyl methacrylate following dermal exposure.
Based on the results of the Preliminary Compatibility Test, the test item characteristics, its usage and on the recommendations of the OECD Guideline no. 429, the test item was tested for formulation compatibility in acetone:olive oil 4:1 (v:v) mixture (abbreviated as AOO). The highest achievable concentration based on the regulatory requirements of the OECD guideline and the physical characteristics of the test item was 100 % (undiluted).
The Preliminary Irritation/Toxicity Tests were performed in CBA/J mice using three doses (2 animals/dose): 100 % (undiluted), 50 and 25 % (w/v) in AOO. Based on the observations recorded in the preliminary test, the 100 % (v/v) was selected as top dose for the main test.
In the main assay, twentyfive female CBA/J mice were allocated to five groups of five animals each:
- three groups received n-octyl methacrylate (formulated in AOO) at 100, 50, and 25 % (v/v) concentrations,
- the negative control group received the vehicle (AOO),
- the positive control group received 25 % (v/v) HCA (dissolved in AOO).
The test item solutions were applied on the dorsal surface of ears of experimental animals (25 µL/ear) for three consecutive days (Days 0, 1 and 2). There was no treatment on Days 3 and 4. At the Day 5, the cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).
No mortality or signs of systemic toxicity were observed during the study. There were no indications of any irritancy at the site of application. No treatment related effects were observed on the body weight changes of experimental animals.
The stimulation index values were 2.55, 4.20 and 4.98 at concentrations of 100, 50 and 25 % (w/v), respectively.
The result of the positive control substance alpha-Hexylcinnamaldehyde (HCA) dissolved in the same vehicle was used to demonstrate the appropriate performance of the assay. A lymphoproliferative response in line with historic positive control data was noted for the positive control chemical, this result confirmed the validity of the assay.
In conclusion, under the conditions of the present assay, n-octyl methacrylate, tested in a suitable vehicle, was shown to have weak sensitisation potential in the Local Lymph Node Assay. The SI obtained for n-octyl methacrylate at 50% (v/v) in acetone:olive oil (4:1 v/v) and 100% n-octyl methacrylate concentrations showed a greater than threefold increase compared to the vehicle control value with an EC3 value found to be 31.82% (v/v) in the LLNA assay.
The following classification/labelling is triggered:
Regulation (EC) No 1272/2008 (CLP) / GHS 2017: Classified as skin sensitiser, Cat.: 1B
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