Registration Dossier

Administrative data

Description of key information

For the endpoint skin and eye irritation no studies with n-octyl methacrylate were available. Therefore a read across using the category approach was used to predict the irritating properties of n-octyl methacrylate. As source substances 2-ethylhexyl methacrylate and n-hexyl methacrylate (n-HMA) were chosen.

n-hexyl methacrylate was tested with respect of its acute dermal irritant/corrosive properties following the patch test method. Method: according to Appraisal of the Safety of Chemicals in foods, drugs  and cosmetics, FDA Draize (1959) (Evonik Oil Additives GmbH, 1978)

In this study n-HMA is a slight to moderate skin irritant.

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.

n-HMA is slightly to moderate irritating in the rabbit eye and 2-EHMA slightly to none irritating. Thus, it can be assumed that the eye irritating property of n-OMA is also in the range of 2 -EHMA as there are no further indicators for stronger irritation. For precautionary reasons n-OMA has to be regarded as slightly irritating in a worst case approach.

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:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
May 15, 2017 - May 22, 2017 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
The degree of skin irritation observed in animals with the C1-C8 methacrylate esters is slight on short exposure to moderate on prolonged exposure of 24 hours, in the rabbit. In humans there is evidence
from Nyquist et al. (1958) that 5% MMA in paraffin and olive oil caused erythema and eczematous reactions. Although there are no relevant, documented data on human experience with the other esters it
is likely that they will be comparable to MMA. For 2-EHMA, a new in vitro study showed the low skin irritation potential with clear negative results.
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
Adopted on 28 July 2015
GLP compliance:
yes
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 TM - 0.38 cm2
- Tissue batch number(s): 17-EKIN-020
- Delivery date: May 16, 2017

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: once, with approximately 25 mL of sterile D-PBS

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2 mL/well
- Incubation time: 3 hours ± 5 minutes
- Spectrophotometer: periodically verified against standard solutions of MTT formazan prepared in acidic isopropanol

NUMBER OF REPLICATE TISSUES: 3

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
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
20 μL if liquid, 20±2 mg if solid -> surface exposure of approximately 53 μL/cm2 or mg/cm2
Duration of treatment / exposure:
15 ± 0.5 minutes
Duration of post-treatment incubation (if applicable):
MTT assay: 3 hours ± 5 minutes
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Value:
95
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
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

Viability range of three test item replicates: 84.7 - 103.3% ; standard deviation 9.4

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
Executive summary:

The potential of the test item 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 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).

NOTE:Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
The degree of skin irritation observed in animals with the C1-C8 methacrylate esters is slight on short exposure to moderate on prolonged exposure of 24 hours, in the rabbit. In humans there is evidence
from Nyquist et al. (1958) that 5% MMA in paraffin and olive oil caused erythema and eczematous reactions. Although there are no relevant, documented data on human experience with the other esters it
is likely that they will be comparable to MMA. For 2-EHMA, a new in vitro study showed the low skin irritation potential with clear negative results.
Qualifier:
according to
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 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 wer  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:
other: 24+72h
Score:
0.9
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:
2.1
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: scarified skin
Irritation parameter:
erythema score
Remarks:
erythema score shaved skin
Basis:
mean
Time point:
other: 24+72 h
Score:
1.66
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Remarks:
edema score scarified skin
Basis:
mean
Time point:
other: 24+72h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: scarified skin
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:
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.

NOTE:Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
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
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
The degree of skin irritation observed in animals with the C1-C8 methacrylate esters is slight on short exposure to moderate on prolonged exposure of 24 hours, in the rabbit. In humans there is evidence
from Nyquist et al. (1958) that 5% MMA in paraffin and olive oil caused erythema and eczematous reactions. Although there are no relevant, documented data on human experience with the other esters it
is likely that they will be comparable to MMA. For 2-EHMA, a new in vitro study showed the low skin irritation potential with clear negative results.
Qualifier:
according to
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 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:
slightly irritating
Remarks:
Migrated information 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.

NOTE:Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Test procedure in accordance with national standard methods with acceptable restrictions. Restrictions: Observation period only 72 h, only two observations, duration of treatment 24 h instead of 4h.
Justification for type of information:
Read across from n-hexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
The degree of skin irritation observed in animals with the C1-C8 methacrylate esters is slight on short exposure to moderate on prolonged exposure of 24 hours, in the rabbit. In humans there is evidence
from Nyquist et al. (1958) that 5% MMA in paraffin and olive oil caused erythema and eczematous reactions. Although there are no relevant, documented data on human experience with the other esters it
is likely that they will be comparable to MMA. For 2-EHMA, a new in vitro study showed the low skin irritation potential with clear negative results.
Qualifier:
according to
Guideline:
other: according to Appraisal of the Safety of Chemicals in foods, drugs and cosmetics, FDA Draize (1959)
Principles of method if other than guideline:
Information about the method, described in the study report ( Draize test: skin irritation/corrosion), is given in the free text field " Any other information materials and methods incl. tables".
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: mean value 2,5 kg
- Housing: individual housing
- Diet: ad libitum standard diet (Mümmel Z, Plange)
- Water: ad libitum
- Acclimation period: no data



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C
- Humidity (%): 45 - 55 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Type of coverage:
occlusive
Preparation of test site:
other: shaved and shaved/abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin areas of the test animals serve as the control (shaved, scarified).
Amount / concentration applied:
undiluted 0.5 mL (equal to 443 mg (density 0.886 g/cm3))
Duration of treatment / exposure:
24 hour(s)
Observation period:
24h and 72h post application
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100% the whole torso of the animal was covered with a gummed bandage
- Type of wrap if used: gummed bandage to wrap up the body of the test animal.
REMOVAL OF TEST SUBSTANCE
- Removal of the test substance by removal of the adhesive tape and the bandage, no wash off

SCORING SYSTEM:
Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Very severe erythema (beef redness) to eschar formation preventing grading of erythema: 4
Maximum possible: 4

Edema Formation
No edema: 0
Very slight edema (barely perceptible) : 1
Slight edema (edges of area well defined by definite raising):2
Moderate edema (raised approximately 1mm): 3
Severe edema (raised more than 1mm and extending beyond area of exposure):4
Maximum possible: 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
48 h value was not determined. No data in respect to reversibilty for times after exposure > 72h. Too short study duration to make a statement about reversibility. Only data of shaved skin have been used, data of shaved and scarified skin have not been used.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.92
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
48 h value was not determined. No data in respect to reversibilty for times after exposure > 72h. Too short study duration to make a statement about reversibility. Only data of shaved skin have been used, data of shaved and scarified skin have not been used.
Irritant / corrosive response data:
Not reported
Other effects:
Not reported

Overall primary irritation score (PDII): 3.6 of 8 scores FDA (Draize), 1959,  

re-evaluated according to OECD 404

Reevaluation of the test results according to OECD404/GHS: only records for the shaved skin (not scarified) were considered  Erythema/ 24h     Erythema/72h  Oedema/24h  Oedema/72h
 animal 1  2  2  0  1
 animal 2  2  2  2  2
 animal 3  1  2  3  2
 animal 4  1  2  3  2
 animal 5  1  2  3  2
 animal 6  1  2  2  1
 average (single scores: animal 1-6)  1,34 2,000  2.17  1,67
 Primary irritation index I = Mean erythema score  (Erythema; 24h, 72h);  out of 4 scores  1,67  Primary irritation index II =  Mean oedema score (Oedema; 24h, 72h);   out of 4 scores  1,92  
 Overall average PDII out of 8 scores; For evaluation according to GHS classification system:  3,6    

Remarks concerning the study result: The study for acute skin irritation/  
corrosion was performed before OECD 404 came into force. For this reason the 
test values were reevaluated according to OECD criteria and test scores 
(erythema, oedema) obtained for the scarified skin were regarded as irrelevant.

  
Classification criteria according to the different classification systems:

EU-GHS:

Category 1: Corrosive subcategories

Corrosive in >= 1 of 3 animals
(applies to authorities not using subcategories): Corrosive
(only applies to some authorities)

Subcategory    Exposure                       Observation
------------------------------------------------------------
1A             <= 3 minutes                   <= 1 hour
1B             > 3 minutes to <= 1 hour       <= 14 days
1C             > 1 hour to <= 4 hours         <= 14 days
------------------------------------------------------------

A: Single harmonized corrosion category, using the results of animal testing.
A: Corrosive is a test substance that produces destruction of skin tissue, namely, 
visible necrosis through the epidermis and into the dermis, in at least 1 of 3 
tested animals after exposure up to 4 hours duration. Corrosive reactions are 
typified by ulcers, bleeding, bloody scrabs and, by the end of observation at 14 
days, by discoloration due to bleaching of the skin, complete areas of alopecia 
and scars. Histopathologic determinations should be consided evaluate questionable 
lesions.

Substances and/or mixtures are considered corrosive (Skin categorry 1) if it has
a pH of 2 or less or a pH of 11.5 or greater. If consideration of alkali/acid 
reserve suggests the substance or prepatration may not be corrosive despite the 
low or high pH value, then further testing needs to be carried out to confirm 
this, preferably by use of an appropriate validated in vitro test.

Category 2:

(1) Mean value of >= 2.3 to < 4.0 for erythem/eschar or for oedema in at least 2 
    of 3 animals from gradings at 24, 48 and 72 hours after patch removal or, if 
    reactions are delayed, from grades on 3 consecutive days after the onset of 
    skin reactions, or
(2) Inflammation that persits to the end of the observation period normally 14
    days in at least 2 animals, particularly taking into account alopecia 
    (limited area), hyperkeratosis, hyperplasia, and scalling, or
(3) In some cases where there is pronounced variability of response amoung 
    animals, with very definite positive effects related to chemical exposure
    in a single animal but less than the criteria above.

UN-GHS (additional category 3):

Category 3: Mild irritant (Applies to only some authorities for e.g. UN-GHS)

Mean value of >= 1.5 to < 2.3 for erythem/eschar or for oedema from gradings
in at least 2 of 3 tested animals from grades at 24, 48 and 72 hours or, if
reactions are delayed, from grades on 3 consecutive days after the onset of
skin reactions (when not included in the irritant category above).

According to the results of this dermal irritation study n-Hexylmethacrylate
has to be classified as follows:


According to EU-GHS (CLP): Hazard category: None (effects < 2.3 both erythem 
                        and oedema)
According to UN-GHS: Hazard category: 3 (Erythem > 1.5 but < 2.3, 24 hour 
                        exposition, no wash off the test substance)











   
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    

ems:

Classification criteria according to the different classification systems:

   

Classification criteria according to the different classification systems:

Classification criteria according to the different classification systems:

 

EU-GHS:

Category 1: Corrosive subcategories

  

Corrosive in >= 1 of 3 animals

(applies to authorities not using subcategories): Corrosive

(only applies to some authorities)

Subcat. Exposure                          Observation

1A    <= 3 minutes                      <= 1 hour

1B     > 3 minutes -- <= 1 hour  <= 14 days

1C     > 1 hour -- <= 4 hours      <= 14 days

A single harmonized corrosion category is provided in Table 3.2.1, using the results of animal

testing. A corrosive is a test material that produces destruction of skin tissue, namely, visible necrosis

through the epidermis and into the dermis, in at least 1 of 3 tested animals after exposure up to a 4 hour

duration. Corrosive reactions are typified by ulcers, bleeding, bloody scabs and, by the end of observation at

14 days, by discoloration due to blanching of the skin, complete areas of alopecia and scars. Histopathology

should be considered to discern questionable lesions.

 

A mixture is considered corrosive (Skin Category 1) if it has a pH of 2 or less or a pH of 11.5 or greater. If

consideration of alkali/acid reserve suggests the substance or preparation may not be corrosive despite the low or high pH value, then further testing needs to be carried out to confirm this, preferably by use of an appropriate validated in vitro test.

Conclusions:
n-Hexyl methacrylate was not irritating in a primary skin irritation study in rabbits (24-hour occlusive application, no wash of the
test substance). No data in respect to reversibilty for times after > 72h observation. Only data of shaved skin have been used, data of shaved and
scarified skin have not been used.
According to the results of this dermal irritation study n-Hexylmethacrylate has to be classified as follows:
According to EU-GHS (CLP): Hazard category: None (effects < 2.3 both erythem and oedema)
According to UN-GHS: Hazard category: 3 (Erythem > 1.5 but < 2.3, 24 hour application, no wash off the test substance) mildly irritating
Executive summary:

In a primary dermal irritation study New Zealand White rabbits were dermally exposed (intact and scarified skin) to

0.5 mL undiluted n-Hexyl methacrylate for 24 hours. Animals then were observed for 3 days. Irritation was scored by the method of Draize et al., 1959.

The mean erythema score (average value of  the single scores (animals 1-6; erythema; intact skin, 24h and 72h)  was determined to be 1.667 out of 4 and the mean oedema score was 1.9167 out of 4.   

Remarks concerning the study result: The study for acute skin irritation/corrosion was performed before OECD 404  came into force. For this reason the  test values were reevaluated according to OECD criteria and test scores  (erythema, oedema) obtained for the scarified skin were regarded as irrelevant.

According to the results of this dermal irritation study n-Hexylmethacrylate has to be classified as follows:

According to GefStoffV: slightly below the irritancy threshold (non-irritant, but 24 hour application, no wash off the test substance)

According to EU-GHS (CLP): Hazard category: None (effects < 2.3 both erythem and oedema)

According to UN-GHS: Hazard category: 3 (Erythem > 1.5 but < 2.3, 24 hour application, no wash off the test substance) mildly irritating.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

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:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
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.
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
The C1-C8 methacrylate esters are slight to mild irritants except for 2-EHMA, which is practically non to slightly irritating.
n-HMA lies between BMA and 2-EHMA of the C1-C8 methacrylate esters. i-BMA and n-BMA are slightly irritating in the rabbit eye and 2-EHMA slightly to none irritating. Thus, it can be assumed that the eye irritating property of n-OMA lies also in the range of 2-EHMA as there are no further indicators for stronger irritation. For precautionary reasons n-OMA has to be regarded as slightly irritating in a worst case approach.
Qualifier:
according to
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:
other: 24+48+72h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Except for some initial redness, none of the animals showed any effects of the treatment.
Interpretation of results:
not irritating
Remarks:
Migrated information 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 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.

NOTE:Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
The C1-C8 methacrylate esters are slight to mild irritants except for 2-EHMA, which is practically non to slightly irritating.
n-HMA lies between BMA and 2-EHMA of the C1-C8 methacrylate esters. i-BMA and n-BMA are slightly irritating in the rabbit eye and 2-EHMA slightly to none irritating. Thus, it can be assumed that the eye irritating property of n-OMA lies also in the range of 2-EHMA as there are no further indicators for stronger irritation. For precautionary reasons n-OMA has to be regarded as slightly irritating in a worst case approach.
Qualifier:
according to
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:
other: 24+48+72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48h
Interpretation of results:
slightly irritating
Remarks:
Migrated information 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.

NOTE:Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Skin irritation

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.

For clarification reasons, the potential of 2-EHMA to be irritant to the skin was investigated through an in vitro skin irritation study according to OECD 439, using a commercial reconstructed human epidermis

(RhE) model named EPISKIN™. The mean cell viability of the test item treated tissues, after the blank subtraction, was 95%. Based on the results obtained, the test item should be classified as not irritant to

the skin (UN GHS No Category).

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 as eye 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 and n-octyl methacrylate 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

For the endpoint skin and eye irritation no studies with n-octyl methacrylate were available. Therefore a read across using the category approach was used to predict the irritating properties of n-octyl methacrylate. As source substances 2-ethylhexyl methacrylate and n-hexyl methacrylate were chosen.

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

 

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