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Administrative data

Description of key information

2-ethylhexyl methacrylate is not an skin irritant and a very slight eye irritant.
2-ethylhexyl methacrylate is not expected to be irritating to the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 15, 2017 - May 22, 2017 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
Adopted on 28 July 2015
GLP compliance:
yes (incl. QA statement)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN™ - 0.38 cm2
- Tissue batch number(s): 17-EKIN-020
- Shipping date: 15 May 2017
- Delivery date: 16 May 2017
- Date of initiation of testing: 15 May 2017

TEMPERATURE USED FOR TEST SYSTEM
- Temperature of post-treatment incubation: 37°C, 5% CO2 and saturated humidity

REMOVAL OF TEST MATERIAL AND CONTROLS
At the end of the exposure, each tissue was rinsed with approximately 25mL of sterile D-PBS,
filling and empting the tissue insert. The excess liquid was carefully removed and the sample
transferred in new wells pre-filled with 2mL/well of maintenance medium.
- Modifications to validated SOP: not indicated in the report

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2mL/well of MTT ready-to-use solution
- Incubation time: approximately 3 hours at 37°C, 5% CO2 and saturated humidity
- Wavelength: 595 nm
- Linear OD range of spectrophotometer: confirmed by MTT formazan calibration curve

NUMBER OF REPLICATE TISSUES: 3

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA
Criteria Classification
Mean relative viability ≤ 50% UN GHS Category 2 or 1
Mean relative viability > 50% UN GHS No Category (for member states that do not adopt optional category 3)
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL, NEGATIVE and POSITIVE CONTROL
- Amount(s) applied: 20 μL (i.e. approx. 53 µL/cm2)
Duration of treatment / exposure:
15 ± 0.5 minutes
Duration of post-treatment incubation (if applicable):
A 42 ± 1 hour recovery period was allowed by incubation at 37°C, 5% CO2 and saturated humidity
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Value:
95
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
Viability range of three test item replicates: 84.7 - 103.3% ; standard deviation 9.4
Other effects / acceptance of results:
- OTHER EFFECTS:
- Colour interference with MTT: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes

Tabulated results

Blank Negative Control        
OD sample OD OD-blank mean Viability (%)
0.037 N1-1 0.696 0.6590    
0.037 N1-2 0.627 0.5900 0.6245 98.7
0.036 N2-1 0.702 0.6650    
0.037 N2-2 0.673 0.6360 0.6505 102.8
0.038 N3-1 0.675 0.6380    
0.037 N3-2 0.647 0.6100 0.6240 98.6
mean 0.037   0.7   0.6 100
SD 0.001   0.03   0.02 2.4
CV (%)  1.7   4.3   2.4 2.4
Positive Control        
sample OD OD-blank mean Viability (%)
P1-1 0.081 0.0440    
P1-2 0.075 0.0380 0.0410 6.5
P2-1 0.068 0.0310    
P2-2 0.065 0.0280 0.0295 4.7
P3-1 0.086 0.0490    
P3-2 0.081 0.0440 0.0465 7.3
mean 0.1   0.04 6
SD 0.01   0.01 2.4
CV (%)  10.8   22.2 22.2
Test item        
sample OD OD-blank mean Viability (%)
A1-1 0.653 0.6160    
A1-2 0.632 0.5950 0.6055 95.7
A2-1 0.592 0.5550    
A2-2 0.554 0.5170 0.5360 84.7
A3-1 0.710 0.6730    
A3-2 0.672 0.6350 0.6540 103.3
mean 0.6   0.6 95
SD 0.06   0.06 9.4
CV (%)  8.8   9.9 9.9
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this GLP conform in vitro study according to OECD 439, the test item 2-EHMA is not irritant to the skin (UN GHS No Category).
Executive summary:

The potential of the test item 2-EHMA to be irritant to the skin was investigated through an GLP conform in vitro skin irritation study according to OECD 439, using a commercial reconstructed human epidermis (RhE) model named EPISKIN™.

The blank, negative and positive controls gave acceptable results and the study was accepted as valid.

The mean cell viability of the test item treated tissues, after the blank subtraction, was 95%.

Based on the results obtained, the test item 2-EHMA is classified as not irritant to the skin (UN GHS No Category).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals  in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize)  (1959).
Deviations:
not specified
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 2.5 kg
- Housing:
- Diet (e.g. ad libitum): Höing 222
- Water (e.g. ad libitum): tap water
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-1
- Humidity (%): 50-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
other: shaved or shaved/scarified
Vehicle:
unchanged (no vehicle)
Controls:
other: two untreated areas (shaved and shaved/scarified) were used as the control
Amount / concentration applied:
undiluted; 0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
24 and 72 hours post dosing
Number of animals:
6
Details on study design:
Six New Zealand White rabbits were assigned to study.  In order to  investigate the reproducibility of the effects, each rabbit had two  separate dose sites (shaved and shaved/scarified), which were treated  with 0.5 ml of undiluted test material.  In addition, two untreated areas (shaved and shaved/scarified) were used as the control.  Only reactions which were different from those of the control were evaluated as positive reactions. For each treated dose site, 0.5 ml of undiluted test material was soaked onto a gauze patch (approx. 6 cm²/1 in²) which was held in  place with adhesive tape on the shaved and shaved/scarified skin of the test animals. The animals were fixed in a holding device and their bodies were wrapped in a rubberised cloth for 24 hours.  After this time dressing and adhesive tape were removed and the local reactions were  examined.  72 hours after application, the examinations were repeated.  The test result is the average of the scores of the 24- and 72-hour examinations.
Irritation parameter:
edema score
Remarks:
edema score shaved skin
Basis:
mean
Time point:
24/48/72 h
Score:
0.9
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: occlusive, 4 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
erythema score
Remarks:
erythema score scarified skin
Basis:
mean
Time point:
24/48/72 h
Score:
2.1
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: occlusive, 4 h exposure, observation time 72 h, scarified skin, mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
erythema score
Remarks:
erythema score shaved skin
Basis:
mean
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: occlusive, 4 h exposure, observation time 72 h, shaved intact skin, mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
edema score
Remarks:
edema score scarified skin
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: occlusive, 4 h exposure, observation time 72 h, scarified skin, mean 24 + 72 h, 48 h was not evaluated.
Irritant / corrosive response data:
Shaved skin: 24 hours after application 5 of 6 animals showed well defined erythema. 72 hours after  application 3 animals had well defined erythema while the other 3 had very slight erythema. Slight edema (and in two cases very slight edema) was present in all animals 24 hours after application. After 72 hours, no edema was observed except for one animal with very slight edema.
Shaved and scarified skin: 24 hours after application all animals showed well defined erythema. 72 hours after application the well defined erythema was still present in 5 of 6 animals while in one case it had developed to moderate to severe erythema. Slight edema (and in one case moderate edema) was present in all animals 24 hours after application. After 72 hours, very slight edema was observed  in all animals.
Interpretation of results:
other: slightly irritating
Remarks:
Not classified: Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Executive summary:

The cutaneous irritation that could be induced by 2-ETHYLHEXYL METHACRYLATE was evaluated in the rabbit according to the "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize) (1959). 2-ETHYLHEXYL METHACRYLATE was applied as supplied, at the dose level of 0.5 ml per animal, under an occlusive patch for 24 hours, to the intact and abraded skin of six New-Zealand albino rabbits. The cutaneous reactions were observed when the patches were removed and were again made at 72 hours. On the shaved skin, 24 hours after application 5 of 6 animals showed well defined erythema. 72 hours after application 3 animals had well defined erythema while the other 3 had very slight erythema. Slight edema (and in two cases very slight edema) was present in all animals 24 hours after application. After 72 hours, no edema was observed except for one animal with very slight edema. On the shaved and scarified skin, 24 hours after application all animals showed well defined erythema, 72 hours after application the well defined erythema was still present in 5 of 6 animals while in one case it had developed to moderate to severe erythema. Slight edema (and in one case moderate edema) was present in all animals 24 hours after application. After 72 hours, very slight edema was observed in all animals. For the shaved skin, the mean scores over 24 and 72 h were 1.66 and 0.9 for erythema and oedema, respectively. Under these experimental conditions, 2-ETHYLHEXYL METHACRYLATE was considered as an slight irritant when applied 24 hours to the rabbit skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets minimum scientific standards for a dermal irritation study and provides sufficient information for assessment
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Labeling Act Regulations, Section 191.12, Federal Register: 29, 13009 (1964)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
no data
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
24 and 72-h post dosing
Number of animals:
6
Details on study design:
Six NZ White rabbits were restrained in stocks and the fur removed by clipping. Half of the exposed area was abraded and the other half remained intact. 0.5 ml(vol) of test compound was applied to the shaved intact and abraded skin sites and covered with surgical gauze. The area  was then wrapped with impervious tape and a stockinette sleeve.  Test material remained in contact for 24 hrs and then removed.  Irritation  scores were determined at 24 and 72 hours after patch removal.
Irritation parameter:
erythema score
Remarks:
erythema score
Basis:
mean
Time point:
other: 24+72h
Score:
1.9
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+72h
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Remarks:
erythema score
Basis:
mean
Time point:
other: 24+72h
Score:
1.9
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: scarified skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+72h
Score:
2.1
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: scarified skin
Irritant / corrosive response data:
The reactions displayed at the first reading interval ranged from barely perceptible to moderate reddening and swelling of the skin, at both intact and abraded sites. Evidence of irritation persisted to the end of the test period in each animal. Examples of a general increase in turgor, discolouration and induration were also identified in this study.
Interpretation of results:
other: slightly irritating
Remarks:
Not classified: Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Executive summary:

The cutaneous irritation that could be induced by 2-ETHYLHEXYL METHACRYLATE was evaluated in the rabbit according to the recommendations of the Federal Hazardous Substances Labelling Act Regulations, Section 191.11, published in the Federal Register (USA) -29 F.R. 13009, 1964.

2-ETHYLHEXYL METHACRYLATE was applied as supplied, at the dose level of 0.5 ml per animal, under an occlusive patch for 24 hours, to the intact and abraded skin of six New-Zealand albino rabbits. The cutaneous reactions were observed when the patches were removed and were again made at 72 hours.

Barely perceptible to moderate reddening and swelling of the skin were exhibited 24 hours following application. Reactions persisted to 72 hours. For the intact skin, the mean scores over 24 and 72 h were 1.9 and 2.2 for erythema and oedema, respectively.

Under these experimental conditions, 2-ETHYLHEXYL METHACRYLATE was considered as an slight irritant when applied 24 hours to the rabbit skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. The test followed recognized toxicology testing procedures and recognized scoring procedures of the results.
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize) (1959)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation:
- Weight at study initiation: 2.4-2.6 kg
- Housing: no data
- Diet (e.g. ad libitum): Mümmel Z, Plange
- Water (e.g. ad libitum): tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 45-55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
Not rinsed
Observation period (in vivo):
24, 48 and 72 h, and 4, 5, 6 and 7 days
Number of animals or in vitro replicates:
6
Details on study design:
Six New Zealand White rabbits had 0.1 ml of undiluted test material  instilled into the conjunctival sac of the left eye. The right eye of  each rabbit, which remained untreated, served as a control. Animals were observed for irritating effects of the cornea, iris, conjunctivae 24, 48  and 72 hours and 4, 5, 6 and 7 days after treatment.

SCORING SYSTEM: Draize scale
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Remarks:
Mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Remarks:
Mean 24 + 72 h, 48 h was not evaluated.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Mean 24 + 72 h, 48 h was not evaluated.
Irritant / corrosive response data:
Except for some initial redness, none of the animals showed any effects of the treatment.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
Based on the results of this non GLP conform in vivo study according to recommendations of the "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize) (1959), the test item 2-EHMA is not irritant to the eye (UN GHS No Category).
Executive summary:

The ocular irritation that could be induced by 2-ethylhexyl methacrylate was evaluated in the rabbit according to the recommendations of the "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize) (1959). A single application of 0.1 ml of 2-ethylhexyl methacrylate in its original form was placed into the conjunctival sac of one eye of six New-Zealand white rabbits. The ocular reactions were observed at 24, 48 and 72 hours and up to 7 days after the instillation. Mean values (24+48+72 h) for ocular irritation were: 0.0 for chemosis, enanthema, congestion and opacity. Under these experimental conditions, 2-ethylhexyl methacrylate was considered as not irritating when administered to the rabbit by ocular route.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Labeling Act Regulations, Section 191.12, Federal Register: 29, 13009 (1964)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
Not rinsed
Observation period (in vivo):
24, 48 and 72 hours post dosing
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: opthalmoscope and 2.0% fluoroscein sodium solution
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48h
Interpretation of results:
GHS criteria not met
Remarks:
Not classified Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
Very sligthly irritating
Executive summary:

The ocular irritation that could be induced by 2-ETHYLHEXYL METHACRYLATEwas evaluated in the rabbit according to the recommendations of the Federal Hazardous Substances Labelling Act Regulations, Section 191.12, published in the Federal Register (USA) -29 F.R. 13009, 1964.A single application of 0.1 mlof 2-ETHYLHEXYL METHACRYLATE in its original form was placed into the conjunctival sac of one eye of six New-Zealand white rabbits. The ocular reactions were observed at 24, 48 and 72 hours after the instillation. Mean values (24+48+72 h) for ocular irritation were 0.11 for chemosis, 0.33 for enanthema and 0.00 for congestion and opacity. Under these experimental conditions, 2-ETHYLHEXYL METHACRYLATE was considered as very slightly irritating when administered to the rabbit by ocular route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

In vitro

For clarification of the available in vivo studies described below, the potential of 2-EHMA to be irritant to the skin was investigated through an in vitro skin irritation study using a commercial reconstructed human epidermis (RhE) model named EPISKIN™. The experimental procedures are based on the OECD Guideline for testing of chemicals no. 439. The test item, as well as controls, were tested for their ability to impair cell viability after an exposure period of 15 minutes followed by a 42 ± 1 hour recovery period. The final endpoint of the assay is the colorimetric measurement of MTT reduction (blue formazan salt) in the test system, being this reaction an index of cell viability. The compatibility of the test item with the test system was confirmed in a preliminary test, where no colouring potential was recorded.

In the Main Assay, the test item was applied as supplied in three replicates at the treatment level of 20 μL/epidermis unit, each measuring 0.38cm2 (treatment level: 53 μL/cm2). Positive and negative controls [a 5% (w/v) sodium dodecyl sulphate solution in water and Dulbecco’s phosphate buffered saline (D-PBS), respectively] were concurrently tested, in the same number of replicates and test conditions at the treatment level of 20 μL/epidermis unit.

In the Main Assay, the negative control gave the expected baseline value (Optical Density values of the three replicates higher than 0.6) and variability [Standard Deviation (SD) of % viability lower or equal to 18], in agreement with the guideline indications. According to the method, the negative control mean value is considered the baseline value of the experiment and thus represents 100% of cell viability. The positive control caused the expected cell death (6% of cell viability when compared to the negative control) and variability (SD of % viability equal to 1.4). Based on the stated criteria (mean viability ≤ 40% and SD of % viability ≤ 18), the assay was regarded as valid. The test item did not induce cell death in any replicate, the mean cell viability after the blank subtraction was 95% when compared to the negative control. Intra-replicate variability was acceptable with a SD of % viability value equal to 9.4 (lower than 18, as stated in the Study Protocol). Based on the results obtained, the test item Visiomer ® EHMA is classified as not irritant to the skin (UN GHS No Category).

 

Earlier in vivo studies

The cutaneous irritation that could be induced by 2-ethylhexyl methacrylate was evaluated in the rabbit according to the "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize) (1959) (Sterner, 1977). 2-ethylhexyl methacrylate was applied as supplied, at the dose level of 0.5 ml per animal, under an occlusive patch for 24 hours, to the intact and abraded skin of six New-Zealand albino rabbits. The cutaneous reactions were observed when the patches were removed and were again made at 72 hours. On the shaved skin, 24 hours after application 5 of 6 animals showed well defined erythema. 72 hours after application 3 animals had well defined erythema while the other 3 had very slight erythema. Slight oedema (and in two cases very slight oedema) was present in all animals 24 hours after application. After 72 hours, no oedema was observed except for one animal with very slight oedema. On the shaved and scarified skin, 24 hours after application all animals showed well defined erythema, 72 hours after application the well defined erythema was still present in 5 of 6 animals while in one case it had developed to moderate to severe erythema. Slight oedema (and in one case moderate oedema) was present in all animals 24 hours after application. After 72 hours, very slight oedema was observed in all animals. For the shaved skin, the mean scores over 24 and 72 h were 1.66 and 0.9 for erythema and oedema, respectively. Under these experimental conditions, 2-ethylhexyl methacrylate was considered as a slight irritant when applied 24 hours to the rabbit skin.

The cutaneous irritation that could be induced by 2-ethylhexyl methacrylate was evaluated in the rabbit according to the recommendations of the Federal Hazardous Substances Labelling Act Regulations, Section 191.11, published in the Federal Register (USA) -29 F. R. 13009, 1964 (Poole, 1981). 2-ethylhexyl methacrylate was applied as supplied, at the dose level of 0.5 ml per animal, under an occlusive patch for 24 hours, to the intact and abraded skin of six New-Zealand albino rabbits. The cutaneous reactions were observed when the patches were removed and were again made at 72 hours. Barely perceptible to moderate reddening and swelling of the skin were exhibited 24 hours following application. Reactions persisted to 72 hours. For the intact skin, the mean scores over 24 and 72 h were 1.9 and 2.2 for erythema and oedema, respectively. Under these experimental conditions, 2-ethylhexyl methacrylate was considered as a slight irritant when applied 24 hours to the rabbit skin.

By analogy to the other esters of the category, for which reversibility has been established, it is assumed that the skin irritation caused by 2 -EHMA will be reversible.

The observation period with 24 hrs occlusive exposure of the two available studies was too short to establish reversibility.

 

Eye irritation

The ocular irritation that could be induced by 2-ethylhexyl methacrylate was evaluated in the rabbit according to the recommendations of the "Appraisal of the safety of chemicals in foods, drugs and cosmetics", Division of Pharmacology, FDA (Draize) (1959) (Sterner, 1978). A single application of 0.1 ml of 2-ethylhexyl methacrylate in its original form was placed into the conjunctival sac of one eye of six New-Zealand white rabbits. The ocular reactions were observed at 24, 48 and 72 hours and up to 7 days after the instillation. Mean values (24+48+72 h) for ocular irritation were: 0.11 for chemosis, 0.33 for erythema and 0.00 for congestion and opacity. Under these experimental conditions, 2-ethylhexyl methacrylate was considered a very slight irritant when administered to the rabbit by ocular route.The ocular irritation that could be induced by 2-ethylhexyl methacrylate was evaluated in the rabbit according to the recommendations of the Federal Hazardous Substances Labelling Act Regulations, Section 191.12, published in the Federal Register (USA) -29 F. R. 13009, 1964 (Poole, 1981). A single application of 0.1 ml of 2-ethylhexyl methacrylate in its original form was placed into the conjunctival sac of one eye of six New-Zealand white rabbits. The ocular reactions were observed at 24, 48 and 72 hours after the instillation. Mean values (24+48+72 h) for ocular irritation were 0.11 for chemosis, 0.33 for erythema and 0.00 for congestion and opacity. Under these experimental conditions, 2-ethylhexyl methacrylate was considered as very slightly irritating when administered to the rabbit by ocular route.

The data support that 2-EHMA is not classified as an eye irritant, while it would be regarded as a member of the Index no. 607-134-00-4 (monoalkyl or monoaryl or monoalkylaryl esters of methacrylic acid with the exception of those specified elsewhere in Annex VI) whose members are classified aseye irritants, category 2.

 

Respiratory tract irritation

Based on the studies summarized above classification as Cat. 3 respiratory irritants (H335) is proposed for MMA, EMA, n- and i-BMA, consistent with their Annex VI entries, while based on its low vapour pressure 2-EHMA is not expected to be irritating to the respiratory tract and no classification is proposed, contrary to the alkyl methacrylate group listing (Index no. 607-134-00-4).

 

Effects on skin irritation/corrosion: not irritating (effects below GHS classification level) Effects on eye irritation: slightly irritating (GHS Cat 3; no classification according to CLP)

Justification for classification or non-classification

According to CLP criteria no classification is warranted for the skin, eye and respiratory tract irritation based on the key studies provided based on data and physico-chemical properties,contrary to the alkyl methacrylate group listing (Index no. 607-134-00-4).

 

According to the criteria of UN-GHS(2009) 2-EHMA is not regarded as skin irritant; no classification for eye irritation.