Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating to rabbits according to OECD testing guideline 404.
Eye irritation: mildly irritating to the eyes of rabbits following the CLP classification scheme.

Respiratory irritation: not expected to cause respiratory irritation.

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: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Qualifier:
according to
Guideline:
other: Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959)
Principles of method if other than guideline:
Method: Appraisal of the safety of chemicals in foods, drugs and cosmetics by the Staff of the Division of Pharmacology, FDA, Hautgiftigkeit nach Draize (1959)
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: 2.5 kg (average)
- Housing: individual cages
- Diet: rabbit standard diet (Höing 222)
- Water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -1 (max. limitation)
- Humidity (%): 50-60
- Photoperiod ( hrs light): 12
Type of coverage:
occlusive
Preparation of test site:
other: shaved, shaved and scarified
Vehicle:
unchanged (no vehicle)
Controls:
other: as a contol 2 areas of the treated animals were also shaved ans scrarified but remained untreated
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume): 0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: rubberized cloth

CONTROL.
- as a contol 2 areas of the treated animals were also shaved and scrarified but remained untreated

REMOVAL OF TEST SUBSTANCE
- Washing : no wahing was done


SCORING SYSTEM:
1. Erythema and scars formation
no erythema 0
very slight erythema 1
clear erythema 2
moderate to severe erythema 3
severe erythema (scarlet red) 4
and slightly scars formation

2. Edema formation
no edema 1
very slight edema 2
moderate edema (thickness ca. 1mm) 3
severe edema (thickness more than 4
1mm, large than the edge of the
contact)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24+72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Remarks on result:
other: before end of test, animal died, not treatment related
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24+72 h
Score:
0
Max. score:
0
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24+72 h
Score:
0
Max. score:
4
Remarks on result:
other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Animal Nr.

 

 

Scores (24 h)

Scores (72 h)

1

shaved

Erythema and scras formation

1

0

 

 

Edema formation

0

0

 

shaved/scarified

Erythema and scras formation

2

1

 

 

Edema formation

1

0

2

shaved

Erythema and scras formation

1

*

 

 

Edema formation

0

*

 

shaved/scarified

Erythema and scras formation

0

*

 

 

Edema formation

0

*

3

shaved

Erythema and scras formation

0

0

 

 

Edema formation

0

0

 

shaved/scarified

Erythema and scras formation

1

0

 

 

Edema formation

1

0

4

shaved

Erythema and scras formation

0

0

 

 

Edema formation

0

0

 

shaved/scarified

Erythema and scras formation

0

1

 

 

Edema formation

0

0

5

shaved

Erythema and scras formation

0

0

 

 

Edema formation

0

0

 

shaved/scarified

Erythema and scras formation

0

0

 

 

Edema formation

0

0

6

shaved

Erythema and scras formation

0

0

 

 

Edema formation

0

0

 

shaved/scarified

Erythema and scras formation

0

0

 

 

Edema formation

0

0

*= animal died prio to the end of the test, death not attributed to the treatment with the substance

  1. Primary irritation index of the shaved skin

 

Animal No.

Primary irritation index

1

0.25

2

0.25*

3

0.00

4

0.00

5

0.00

6

0.08

 

 

X1

0.08

 

 

  1. Primary irritation index of the shaved/scarified skin

 

Animal No.

Primary irritation index

1

1.00

2

0.00*

3

0.50

4

0.25

5

0.00

6

0.00

 

 

X2

0.29

 

Total index: X+   X2= 0.37

 * = fragmentary value

Reevaluation according to OECD 404

 

 

Erythema

 

Edema

 

 

24h

72h

24h

72h

Tier 1

1

0

0

0

Tier 2

1

*

0

*

Tier 3

0

0

0

0

Tier 4

0

0

0

0

Tier 5

0

0

0

0

Tier 6

0

0

0

0

Mean

0,33333333

0

0

0

 

 

 

 

 

Total mean

0,16666667

 

0

 

 

Erythema

 

Edema

 

 

 

 

 

 

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
Classification: not irritating
Executive summary:

2 -Hydroxyethyl methacrylate was tested in a primary skin irritation test to rabbits according to "Appraisal of the safety of chemicals in food, drugs and cosmetics by the Staff of the Division of Parmacology, FDA, 1959 in food, drugs and cosmetics". 6 animals were treated with the test substance for 24 h, occlusive. After 24 hours, 2 animals showed slight erythema (one of them died during the test not related to the test substance). Within 72 hours erythema were fully reversible. None of the 6 animals showed edema during the test.

According CLP criteria 2 -Hydroxyethyl methacrylate is not irritating to skin.

 

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data are given.
Qualifier:
according to
Guideline:
other: Appraisal of the safety of Chemicals in foods, drugs and cosmetics by staff of the Division of Pharmacology, FDA acc. to Draize
Principles of method if other than guideline:
Appraisal of the safety of Chemicals in foods, drugs and cosmetics by staff of the Division of Pharmacology, FDA acc. to Draize (1959)
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: no data
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: individual cages
- Diet : standard diet (Höing 222)
- Water ad libitum:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 °C
- Humidity (%): 50-60
- Photoperiod hrs light): 12

Vehicle:
unchanged (no vehicle)
Controls:
other: the right ear of the test animals remained untreated as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume): 0.1 ml
- Concentration: undiluted

Observation period (in vivo):
24, 48, 72 h, 4, 5, 7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no washing:


SCORING SYSTEM:
Scoring system for the evaluation of ear lesions Scores

1. Cornea
A. Opacity - Grade of opacity (the most opac area will be used for evaluation)

No opacity 0
Motteled or diffuse opacity
(details if iris good visible) 1
Slightly differentiated opac areas,
details of iris slightly ambiguous 2
Opac areas, no details of iris are visible,
size of pupil hardly visible 3
Opacity, iris unvisible 4

B. Size of involved total area
¼ or less but not zero 1
More than ¼, but less than ½ 2
Larger than ½ but less than ¾ 3
Larger than ¾ up to total area 4
A x B x 5 total maximum number = 80

2. Iris
A. Evaluation
Normal 0
Increasing wrinkle formation (washy trabecules )
Blood overfilling, swelling, vascular dilatation at
the edge of cornea (when one or more symptoms
occur) iris shows still light reaction (delayed
reaction is deemed to be positive) 1
No reaction against light, bleeding, changes in
iris structure (one or more symptoms) 2

A x 5 total maximum number =10

3. Conjunctiva
A. Redness
Vascular normal 0
Vascular definitely more than normal injected 1
More diffuse crimson colour, single vascular
difficult to identify 2
Diffuse flesh colour 3

B. Chemosis
No swelling 0
More than normal swelling (including nictitating membrane) 1
Definite swelling with lifting the lids 2
Swelling with semi-closed lids 3
Swelling that lids are more than semi-closed or totally
closed 4

C. Secretion
No secretion 0
Every increased secretion (not included the physiological
secretion at the inner canthus) 1
Secretion with moistening the lids and the
neighboring hairs 2
Secretion with wettening the lids and the neighboring
hairs largely beyond the eye 3

Total number (A+B+C) x 2 total maximum number = 20
The total number for the eye is the summation of the scores for cornea, iris and conjunctiva


Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: # 2, '3, #4, #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal: #1, #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal: #2, #3, #4, #6
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: #2, #3, #4, #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days

 

 

Day

Animal No. 1

 

1

2

3

4

5

6

7

1. Cornea

A

1

1

2

1

1

0

0

 

B

4

4

4

4

4

0

0

2. Iris

A

1

1

1

0

0

0

0

3. Conjunctiva

A

3

3

3

2

0

0

0

 

B

2

2

1

0

0

0

0

 

C

2

2

1

0

0

0

0

 

 

 

Day

Animal No. 2

 

1

2

3

4

5

6

7

1. Cornea

A

1

1

1

1

1

0

0

 

B

4

4

4

4

4

0

0

2. Iris

A

1

1

0

0

0

0

0

3. Conjunctiva

A

3

2

0

0

0

0

0

 

B

2

1

0

0

0

0

0

 

C

2

2

1

0

0

0

0

 

 

 

Day

Animal No. 3

 

1

2

3

4

5

6

7

1. Cornea

A

1

1

1

1

1

0

0

 

B

4

4

4

4

4

0

0

2. Iris

A

1

1

0

0

0

0

0

3. Conjunctiva

A

3

2

0

0

0

0

0

 

B

2

1

0

0

0

0

0

 

C

2

2

0

0

0

0

0

 

 

 

Day

Animal No. 4

 

1

2

3

4

5

6

7

1. Cornea

A

1

1

1

1

1

0

0

 

B

4

4

4

4

4

0

0

2. Iris

A

1

1

0

0

0

0

0

3. Conjunctiva

A

2

2

0

0

0

0

0

 

B

2

1

0

0

0

0

0

 

C

2

2

0

0

0

0

0

 

 

 

Day

Animal No. 5

 

1

2

3

4

5

6

7

1. Cornea

A

2

2

2

2

2

0

0

 

B

4

4

4

4

4

0

0

2. Iris

A

1

1

1

1

1

0

0

3. Conjunctiva

A

3

3

3

3

3

0

0

 

B

3

2

2

2

3

0

0

 

C

2

3

3

3

3

0

0

 

 

 

Day

Animal No. 6

 

1

2

3

4

5

6

7

1. Cornea

A

1

1

1

0

0

0

0

 

B

4

4

3

0

0

0

0

2. Iris

A

1

1

0

0

0

0

0

3. Conjunctiva

A

3

3

0

0

0

0

0

 

B

2

1

0

0

0

0

0

 

C

2

2

0

0

0

0

0

 

 

 

Summary of the eye observations

 

Day

Animal No.

1

2

3

4

5

6

7

1

39

39

55

24

20

0

0

2

39

35

22

20

20

0

0

3

39

35

20

20

20

0

0

4

37

35

20

20

20

0

0

5

61

61

61

61

63

0

0

6

39

37

15

0

0

0

0

Mean

42.33

40.33

32.17

24.14

23.83

0

0

 

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
Classification: irritating to eyes, Category 2, H319
Executive summary:

2 -Hydroxyethyl methacrylate was tested in an eye irritation test to rabbits according to the Appraisal of the safety of Chemicals in foods, drugs and cosmetics by staff of the Division of Pharmacology, FDA acc. to Draize (1959). The study was reevaluated according to CLP criteria. The substance is irritating to eyes Catergory 2 (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

HEMA has been evaluated in skin irritation studies in experimental animals.

 

The skin irritation potential of HEMA has been evaluated in tests in rabbits according to OECD 404. This study (Evonik Rohm, 1977) was assigned a Klimisch rating of 2, reliable with restriction. Undiluted HEMA was applied with occlusion to the scarified and non-scarified skin of six rabbits for 24 hr. HEMA was found to be not irritating to the skin of rabbits according to CLP classification criteria. Other available studies were reviewed and judged to be not reliable or not assignable. 

HEMA has been evaluated in eye irritation studies in experimental animals. This study (Evonik Rohm, 1977) was assigned a Klimisch rating of 2, reliable with restriction. 2 -Hydroxyethyl methacrylate was tested in an eye irritation test to rabbits according to the Appraisal of the safety of Chemicals in foods, drugs and cosmetics by staff of the Division of Pharmacology, FDA acc. to Draize (1959). The study was reevaluated according to UN-GHS criteria. The substance is irritating to eyes Catergory (CLP).

HEMA is regarded as mildly irritating to eyes based on studies in rabbits.


Effects on eye irritation: slightly irritating

Justification for classification or non-classification

HEMA was found to be not irritating to the skin of rabbits according to CLP classification criteria.

HEMA is regarded as mildly irritating to eyes based on studies in rabbits. The substance is irritating to eyes (CLP category 2; mildy irritating/ Catergory 2B according to UN-GHS).