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Description of key information

In a well-conducted study, the substance induced severe erythema, oedema and necrosis 24 h after application. For all animals, the maximum score of 4 was noted for erythema and oedema. The reactions persisted to 72 hours.

In a well conducted study, severe corneal, iris and conjuctival lesions were displayed within 2 hours of instillation. The study was terminatined after 2 h. It is reasonable to assume, that similar level of injury would be induced if full scale testing would be conducted. Therefore, the substance is judged as eye corrosive.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
guideline study with acceptable restrictions
Remarks:
Non-GLP, no details on test substance incl. purity, 48-hour reading missing, short observation period).
Principles of method if other than guideline:
According to the method described in the Federal Hazardous Substances Labelling Act Regulations, Section 191.11, published in the Federal Register - 29 F.R. 13009, 1964.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
No details.
Type of coverage:
occlusive
Preparation of test site:
other: intact (shaved) and abraded
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: undiluted
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
4
Details on study design:
A 0.5 mL sample of the test material was applied to areas of intact and abraded areas of skin. These areas were then occluded with square surgical gauge patches, each measuring 1 inch x 1 inch. After 24 hrs exposure, the patches were removed and the resulting reactions evaluated. The valuation was done again at 72 hrs.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
other: not examined
Remarks on result:
other: Observation period too short for a clear conclusion on reversibility.
Remarks:
Only time point 24 and 72 hours were observed.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
other: not examined
Remarks on result:
other: Observation period too short for a clear conclusion on reversibility.
Remarks:
Only time point 24 and 72 hours were observed.
Irritant / corrosive response data:
Severe erythema, oedema and necrosis were exhibited 24 hrs following application. Reactions persisted to 72 hrs. For all animals and for both of
intact skin and abraded skin, maximum score of 4 was marked in the erythema and oedema rating, therefore a Primary Irritation Score of 8.0 was obtained.

Individual skin responses:

 

Rabbit No.

Time

(hours)

Intact Skin

Abraded Skin

Erythema

Oedema

Erythema

Oedema

1

24

4

4

4

4

72

4

4

4

4

2

24

4

4

4

4

72

4

4

4

4

3

24

4

4

4

4

72

4

4

4

4

4

24

4

4

4

4

72

4

4

4

4

5

24

4

4

4

4

72

4

4

4

4

6

24

4

4

4

4

72

4

4

4

4

Mean

24

4

4

4

4

72

4

4

4

4

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
The test material is considered to be corrosive to the 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:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Restrictions: Exposure period 24 hours, 48-hour reading missing, short observation period (72 hours).
Principles of method if other than guideline:
Draize test according to "Appraisal of the safety of chemicals in foods, drugs and cosmetics", by the staff of the Division of Pharmacology, FDA.
GLP compliance:
no
Specific details on test material used for the study:
TEST MATERIAL:
- Name of test material (as cited in study report): 2-dimethylaminoethyl methacrylate
- Physical state: colourless, clear liquid
- Purity: not specified
- Supplier: Röhm GmbH
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 2.5 kg
- Housing: single housing
- Diet: standard rabbit diet (Höing 222) ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1°C
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
other: shaved/intact and shaved/abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated contact sites of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: undiluted
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: rubberised cloth


SCORING SYSTEM: according to Draize (1959).
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
3.33
Max. score:
4
Reversibility:
other: not examined
Remarks on result:
other: Observation period too short for a clear conclusion on reversibility.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
2.58
Max. score:
4
Reversibility:
other: not examined
Remarks on result:
other: Observation period too short for a clear conclusion on reversibility.
Irritation parameter:
other: Draize index
Score:
5.9
Remarks on result:
other: Draize index 5.9 of 8 (reevaluated according to OECD guideline 404).

Re-evaluation of the skin irritation test with 2-dimethylaminoethyl methacrylate:

Remark: Consideration of shaved/intact skin readings only

 

Animal No.

Erythema

Edema

24 h

72 h

24 h

72 h

1

0

0

0

0

2

4

4

3

3

3

4

4

3

3

4

4

4

3

3

5

4

4

3

3

6

4

4

4

3

Mean

3.33

3.33

2.67

2.5

Total mean

3.33

2.58

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
The TS is considered to be highly irritating to the rabbit skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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: Comparable to guideline study with acceptable restrictions (non-GLP, no details on test substance incl. purity, only 2-hour reading, short observation period).
Principles of method if other than guideline:
According to the method described in the Federal Hazardous Substances Labelling Act Regulations, Section 191.11, published in the Federal Register - 29 F.R. 13009, 1964.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No details.
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: undiluted
Duration of treatment / exposure:
2 hours
Observation period (in vivo):
2 hours
Number of animals or in vitro replicates:
2 females
Details on study design:
0.1 mL of the test substance was instilled into one eye of each animal. The lids were gently held together for one second and the eye was then rinsed
with 20 mL Iukewarm water at 4 seconds after instillation. The eyes were examined 2 hrs after instillation. The scoring system used was that according to Draize.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 2 hours
Score:
3
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 2 hours
Score:
4
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 2 hours
Score:
2
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 2 hours
Score:
2
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 2 hours
Score:
3
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 2 hours
Score:
3
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 2 hours
Score:
3
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 2 hours
Score:
4
Reversibility:
other: not examined
Remarks on result:
other: The observation period was too short for a clear conclusion on the reversibilty of the irritation parameters (termination of study 2 hours after administration of the test substance).
Irritant / corrosive response data:
Despite the rinsing treatment severe corneal, iris and conjunctival lesions were displayed by both animals within 2 hrs of instillation. The test was
terminated at this point. lt is reasonable to assume that similar levels of injury would be produced if full scale testing were conducted, and that the
product would be classified as corrosive to the eye.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
It is reasonable to assume that similar levels of injury would be produced if full scale testing were conducted, and that the product would be classified as corrosive to the eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

There are three reports available. Among these, the study by Atochem was identified as the key study because it was conducted according to the recommendations of the Federal Hazardous Substances Labelling Act Regulations, Section 191.11, published in the Federal Register (USA)-29 FR13009, 1964 (Atochem, 1980). The test substance was administrated to the intact and abraded skin of New-Zealand albino rabbits at the dose level of 0.5 mL per animal under an occlusive patch for 24 hours. The cutaneous reactions were observed just after the removal of the patch and after 72 hours. Severe erythema, oedema and necrosis were observed after the test, and these symptoms persisted to the inspection after 72 hours of the test. The obtained primary irritation score was 8.0. Under these test conditions, the test substance was considered to be corrosive to the skin.

In a second study in rabbits according to the method of Draize the test substance was considered to be highly irritating to the skin (Roehm, 1977). The test substance furthermore tested on the skin of guinea pigs resulting in highly irritating effects (Roehm, 1977).

Eye irritation:

The only study available was considered to be reliable because it was conducted in accordance with the recommendations of the Federal Hazardous Substances Labelling Act (Atochem, 1980). Severe cornea, iris and conjunctivae lesions were displayed in both rabbits within 2 hours after the instillation of 0.l mL undiluted test substance into the eye. The test substance was considered to be corrosive to the eyes.

Justification for classification or non-classification

According to Annex VI of EC/1272/2008 (CLP-regulation), the test substance is classified as irritating to skin (Skin Irrit 2, H315) and irritating to eyes (Eye Irrit 2, H319). However, based on the results of two skin irritation studies in rabbits (Atochem, 1980; Roehm, 1977) and one eye irritation study in rabbits (Atochem, 1980), the test substance is considered to be corrosive to skin and eyes. Therefore, the following classification of the test substance is suggested (self-classification):

GHS classification according to Annex I of EC/1272/2008:

- Skin Corr 1B, H314

- Eye Dam1, H318

- Respiratory irritation: No classification required.