Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating;  OECD 404, occlusive, non GLP (Klimisch score = 2) (IBR, 1986)
Skin irritation: not irritating; OECD 404, semi-occlusiv, GLP (Klimisch score = 1) (CIT, 1991)
Eye irritation: not irritating; OECD 405, GLP, Limited documentation (Klimisch score = 2) (ElfAtochem, 1998)
Based on the available data, Ethyltriglycol methacrylate is not irritating to the skin and eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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:
other: Guideline study with acceptable restrictions. Non GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: according to Appraisal of the Safety of Chemicals in foods, drugs and cosmetics, FDA Draize (1959)
Deviations:
no
Principles of method if other than guideline:
Method: according to Appraisal of the Safety of Chemicals in foods, drugs and cosmetics, FDA Draize (1959)
Information about the method, described in the study report ( Draize test: skin irritation/corrosion), is given in the free text field "methods and
materials".
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: New Zealand white rabbits,Schriever Kaninchenfarm, Bremervörde, Germany
- Age at study initiation: no data
- Weight at study initiation: 2.4 - 2.8 kg
- Housing: Single caging in battery of cages with paper roll disposal system
- Diet: ad libitum, Mümmel Z Kaninchenzuchkorn, Saniff Spezialfutter GmbH, Soest, Westfalen, Germany
- Water: ad libitum, quality as for humann consumption
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ±2 °C
- Humidity (%): 50 - 85 %
- 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
Duration of treatment / exposure:
4 hour(s)
Observation period:
4h, 28h, 52 h and 76h post application
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: the whole trunk of the animal was covered with a gummed bandage
- Type of wrap if used: rubber sleeve 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
Remarks:
out of 6 animals
Time point:
other: 4 hours
Score:
0
Max. score:
4
Remarks on result:
other: Only data of shaved skin have been used, data of shaved and scarified skin have not been used.
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of 6 animals
Time point:
other: 4 hours
Score:
0
Max. score:
4
Remarks on result:
other: Only data of shaved skin have been used, data of shaved and scarified skin have not been used.

Overall primary irritation score (PDII): 0 of 8 scores FDA (Draize), 1959,  evaluation according to OECD 404

Evaluation of the test results according to OECD404/GHS: only records for the shaved skin (not scarified) were considered  Erythema/ 28h     Erythema/76h  Oedema/28h  Oedema/76h
 animal 1  0  0  0  0
 animal 2  0  0  0  0
 animal 3  0  0  0  0
 animal 4  0  0  0  0
 animal 5  0  0  0  0
 animal 6  0  0  0  0
 average (single scores: animal 1-6)  0 0  0  0
 Primary irritation index I = Mean erythema score  (Erythema; 24h, 72h);  out of 4 scores  0  Primary irritation index II =  Mean oedema score (Oedema; 24h, 72h);   out of 4 scores  0  
 Overall average PDII out of 8 scores; For evaluation according to GHS classification system:  0    

 
    
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 Ethyltriglycol 
methacrylate has to be classified as follows:

According to GefStoffV: non-irritant (4 hour exposition, 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: None(Erythem 0, 4 hour exposition, no wash off the test substance)
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Ethyltriglycol methacrylate was not irritating in a primary skin irritation study in rabbits (4-hour occlusive application, no wash of the test substance). 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 Ethyltriglycol methacrylate has to be classified as follows:
According to GefStoffV: non-irritant (4 hour occlusive 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: None (4 hour occlusive application, no wash off the test substance) not 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 Ethyltriglycol methacrylate for 4 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, 28h and 76h) was determined to be 0 out of 4 and the mean edema score was 0 out of 4.   

Remarks concerning the study result: The study for acute skin irritation/corrosion was performed according to OECD 404. The test values were evaluated 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 Ethyltriglycol methacrylate has to be classified as follows: According to GefStoffV: non-irritant (4 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: None (4 hour application, no wash off the test substance) not 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
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study OECD 405. GLP. Meets generally accepted scientific principles, acceptable for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24 February 1987
Deviations:
no
GLP compliance:
yes
Remarks:
adopted 12th May 1981
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits, Supplier: Elevage Cunicole du Val de Selle, 80160 Prouzel, France
- Age at study initiation: no data
- Weight at study initiation: 2.9 ±0.05 kg
- Housing: individually in polystyrene cages (35 x 55 x 32 cm or 48.2 x 58 x 36.5 cm)
- Diet: ad libitum during study
- Water: ad libitum during study
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3 °C
- Humidity (%): 50 ±20 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each treated animal serves as controll
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
The eyes were not rinsed after administration of the test substance.
Duration of treatment / exposure:
72 hour(s)
Observation period (in vivo):
21 days after treatment
Number of animals or in vitro replicates:
3
Irritant / corrosive response data:
One hour after instillation of the test substance, some moderate conjunctival reactions (chemosis and redness, score of 2) in 2 animals and marked conjuctival reactions (chemosis, score of 4 and redness, score of 3) in one animal were observed. No iridic or corneal damages were noted in the 3 animals. No ocular reactions were noted thereafter (24, 48 and 72 hours after instillation).

MMAS (Modified Maximum Average Score) (0+0+0)/3 = 0

Classification of eye irritation studies according OECD-GHS-criteria

Substance: Ethyltriglycol methacrylate                                                     CAS: 39670 -09 -2

Internal No.: LITSU 01-0120

Date/Expert: 06 -02 -2012/RG

Animal No.

Corneal opacity/Hornhauttrübung[Scores]

Mean Draize score

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

1

0

0

0

0

-

-

2

0

0

0

0

-

-

3

0

0

0

0

-

-

none

 

Animal No.

Iritis/Regenbogenhautentzündung[Scores]

Mean Draize score

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

1

0

0

0

-

-

2

0

0

0

0

-

-

3

0

0

0

0

-

-

none

Animal No.

Conjunctiva redness (erythem) /Bindehautrötung[Scores]

Mean Draize score

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

1

0

0

0

0

-

-

2

0

0

0

0

-

-

3

0

0

0

0

-

-

none


Animal No.

Conjunctiva chemosis /Bindehautödem[Scores]

Mean Draize score

Reversibility

[scores]

Hazard category

after 24 h

after 48 h

after 72 h

in 7 days

in 21 days

1

0

0

0

0

-

-

2

0

0

0

0

-

-

3

0

0

0

0

-

-

             

 none

Classification:

Hazard Category

none

Classification Criteria for serious Eye Damage

Category 1

- Irreversible damage to cornea, iris, conjunctiva 21 days after exposure in at least one animal

- Mean Draize score in 2 of 3 animals:

corneal opacity 3

iritis ≥ 1,5

Category 2

- Reversible adverse effects on cornea, iris, conjunctiva

- Mean Draize score in 2 of 3 animals:

corneal opacity >= 1

iritis >= 1

redness >= 2

chemosis >= 2

Subcategory 2A

- Reversible in 21 days

Subcategory 2B

- Reversible in 7 days

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification: not irritating
Executive summary:

In a primary eye irritation study according to OECD 405 0.1 mL undiluted Ethyltriglycol methacrylate was instilled into the conjunctival sac of the left eye of 3 New Zealand White rabbits, (body weight at study initiation: 2.9 ±0.05 kg) for 72 hours. The animals were observed for 21 days. Irritation was scored according to Draize scoring and evalutated according OECD-GHS criteria.

In this study Ethyltriglycol methacrylat is not irritating to eyes.

OECD GHS Category: none

EU GHS Category: none

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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Reliable (Klimisch score = 1 and 2), relevant and adequate data are available for the skin and eye irritation potential of Ethyltriglycol methacrylate.

Skin irritation

In a primary dermal irritation study New Zealand White rabbits were dermally exposed (intact and scarified skin) to 0.5 mL undiluted Ethyltriglycol methacrylate for 4 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, 28h and 76h)  was determined to be 0 out of 4 and the mean edema score was 0 out of 4. (Klimisch score = 2) (IBR, 1986)

In a second primary guideline (according to OECD 404) dermal irritation study 3 New Zealand White rabbits were dermally exposed to intact clipped skin with 0.5 mL undiluted Ethyltriglycol methacrylate for 4 hours.

The test sites were covered with a semi-occlusive dressing for 4 hours.

Animals then were observed for 1, 24, 48 and 72 hours after removal of the semi-occlusive dressing. Irritation was scored by the method of OECD guideline 404.

Mean scores over 24, 48 and 72 hours for each animal were 0.0; 0.0 and 0.67 for erythema and 0.0; 0.0 and 0.0 for edema. The irritations were fully reversible within 72 hours.

Based on the available test data Ethyltriglycol methacrylate is not irritating. Hence, Ethyltriglycol methacrylate is not regarded as irritating to the skin according to the criteria of EU Directive 67/548/EEC and the CLP Regulation (1272/2008/EC).

Eye irritation

In a primary eye irritation study according to OECD 405 0.1 mL undiluted Ethyltriglycol methacrylate was instilled into the conjunctival sac of the left eye of 3 New Zealand White rabbits, (body weight: no data) for 72 hours. The animals were observed for 21 days. Mean scores calculated for each animal were 0.0, 0.0 and 0.0 for chemosis, 0.0, 0.0 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. (Klimisch score = 2) (ElfAtochem, 1998)

Based on the available test data Ethyltriglycol methacrylate is not irritating. Hence, Ethyltriglycol methacrylate is not regarded as irritating to the eye according to the criteria of EU Directive 67/548/EEC and the CLP Regulation (1272/2008/EC).


Justification for selection of skin irritation / corrosion endpoint:
There are two reliable key studies available one study: OECD 404, occlusive, Non GLP and a second study: OECD 404, semi-occlusiv, GLP.

Justification for selection of eye irritation endpoint:
Only one key study available; OECD 405, GLP.

Justification for classification or non-classification

In two studies one with GLP and one non-GLP skin irritation studies conducted according to standard acute method (according to OECD 404), no signs of skin irritation were observed. In a further study with GLP according to OECD 405 (standard acute method) no adverse effects of eye irritation were observed. These results do not lead to classification. Therefore, Ethyltriglycol methacrylate is not classified according to the Annex I to the Directive 67/548/EEC and annex VI of the CLP Regulation (1272 /2008/EC).