Registration Dossier

Administrative data

Description of key information

Skin: OECD 404 guideline study, rabbits, exposure for 24h under occlusive dressing: slightly irritating but no classification is required.
Eye: OECD 405 guideline study, rabbits, irreversible ocular effects in all three animals.

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
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is a screening test but followed international guidance requirements with acceptable restrictions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: 24h exposure under occlusive patch conditions, no certificate of analysis
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
other: New Zealand Albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: young adults
- Weight at study initiation: 1500-2500 g
- Housing: individually housed in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES: From: To: no data
Type of coverage:
occlusive
Preparation of test site:
other: abraded and unabraded areas
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL liquid) or 0.5g (solid)
- Concentration (if solution): not applicable as the test substance is applied as supplied

VEHICLE
Not applicable
Duration of treatment / exposure:
24h
Observation period:
48h after the patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: abdomen
- % coverage: one inch square, two application sites on the right side (abraded skin) and two application sites on the lef side (unabraded skin)
- Type of wrap if used: the test sample is applied on a coton gauze which is held in place with adhesive tape. The entire trunk of the animal is then wrapped wih a rubberized cloth

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Remarks:
unabraded skin
Basis:
animal #1
Time point:
other: mean 24/72h after the start of the exposure
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
observations were made at 24h and 72h after the start of exposure
Irritation parameter:
erythema score
Remarks:
unabraded skin
Basis:
animal #2
Time point:
other: mean 24/72h after the start of the exposure
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
observations were made at 24h and 72h after the start of exposure
Irritation parameter:
erythema score
Remarks:
unabraded
Basis:
animal #3
Time point:
other: mean 24/72h after the start of the exposure
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
observations were made at 24h and 72h after the start of exposure
Irritation parameter:
edema score
Remarks:
unabraded skin
Basis:
animal #1
Time point:
other: mean 24/72h after the start of the exposure
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
observations were made at 24h and 72h after the start of exposure
Irritation parameter:
edema score
Remarks:
unabraded skin
Basis:
animal #2
Time point:
other: mean 24/72h after the start of the exposure
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
observations were made at 24h and 72h after the start of exposure
Irritation parameter:
edema score
Remarks:
unabraded skin
Basis:
animal #3
Time point:
other: mean 24/72h after the start of the exposure
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
observations were made at 24h and 72h after the start of exposure
Irritant / corrosive response data:
See details in Tables 7.3.1/1 and 7.3.1/2
Other effects:
no data

Table 7.3.1/1:Irritant/corrosive response data for each animal at each observation time after the topical application of the test substance on unabraded skin

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

24 h

1/2/2

1/2/2

72 h

0/0/0

0/0/0

Average 24h and 72h

0.5/1.0/1.0

0.5/1.0/1.0

Reversibility

Yes

Yes

 

Table 7.3.1/2:Irritant/corrosive response data for each animal at each observation time after the topical application of the test substance on abraded skin

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

24 h

1/2/2

1/2/2

72 h

1/1/1

0/0/0

Average 24h and 72h

1/1.5/1.5

0.5/1.0/1.0

Reversibility

No data

Yes

 

The primary dermal irritation index (PDII) was 1.92.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test item Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified as skin irritant when applied topically to rabbits according to the criteria of the CLP regulation (EC) 1272/2008 and to the criteria of the Directive 67/548/EEC.
Executive summary:

In a dermal irritation study performed similarly to the OECD guideline No. 404, 3 New Zeland Albino rabbits, were dermally exposed to 0.5 mL of undiluted Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide.

Prior to the topical application, the skin of the rabbit was prepared with a clipper to remove the hair. After clipping, the right side of the animal was prepared by making epidermal abrasions, while the left site remained intact (clipped but unabraded). The test substance was then applied on the skin (abraded or not) on two different application sites (4 application sites in total on each animal). Then the test sites were covered with an occlusive dressing for 24 hours. Those exposure conditions correspond to a worst case approach as the test guidance recommends an exposure under semi-occlusive patch and for4h.Skin irritation was assessed and scored according to the Draize scale at 24 and 72 hrs after the topical application of the test patch.  

The mean individual scores calculated within 2 scoring times (24 and 72 hrs) for the unabraded skin were 0.5/1.0/1.0 for erythema and 0.5/1.0/1.0 for edema.

Under the test conditions, the test item Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified as skin irritant when applied topically to rabbits according to the criteria of the CLP regulation (EC) 1272/2008 and to the criteria of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

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
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is a screening test but followed international guidance requirements with acceptable restrictions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: observation period of 14 days rather than 21 days, no certificae of analysis
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Species:
rabbit
Strain:
other: New Zealand Albino
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
other: the lef untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not applicable as the test item is instilled as supplied

VEHICLE
not applicable
Duration of treatment / exposure:
No wash is performed
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
no wash

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible
Remarks:
within 72h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within:
Remarks:
14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
14 days
Irritant / corrosive response data:
Irreversible effects are observed in all three rabbits. See details in Table 7.3.2/1.
Other effects:
no other effects

Table 7.3.2/1:Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test.

 

Score at time point / Reversibility

Cornea

Iris

Conjunctivae redness

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

1/2/2

1/1/1

2/2/2

2/3/3

48 h

1/2/2

1/1/1

2/2/2

2/3/3

72 h

1/2/2

0/1/1

2/2/2

2/3/3

7 days

2/2/2

0/2/1

2/2/2

1/2/1

14 days

2/2/2

0/2/1

1/2/2

0/2/1

Average 24h, 48h, 72h

1/2/2

0.7/1/1

2/2/2

2/3/3

Reversibility*)

n

n

n

n.c

Average time (day) for reversion

N/A

N/A

N/A

N/A

 *) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the test conditions, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is classified as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP) and as Xi, R41 according to the Directive 67/548/EEC as irreversible effects on the eyes are observed in all 3 animals.
Executive summary:

In an eye irritation study performed similarly to the OECD No. 405 guideline, 0.1 mL of undiluted Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide was instilled into the right eye of 3 Albino New Zealand Rabbits.

The eyes were not washed following the instillation of the substance.

Animals were then observed for 14 days for redness, chemosis and discharge of the conjonctiva, corneal opacity and iris lesion. 

Eye irritation was assessed and scored according to the Draize scale at 24, 48 and 72 hrs after the instillation of the substance and then at days 7 and 14. The mean individual score were calculated within 3 scoring times (24, 48 and 72 hrs).

The mean individual scores were 1.0/2.0/2.0 for chemosis, 0.7/1.0/1.0 for iris lesion, 2.0/2.0/2.0 for conjunctival redness, and 2.0/3.0/3.0 for corneal opacity. All of these effects were not reversible within the termination of the study (14 days) in all animals.

Under the test conditions, Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is classified as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP) and as Xi, R41 according to the Directive 67/548/EEC as irreversible effects on the eyes are observed in all 3 animals.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a dermal irritation study performed similarly to the OECD guideline No. 404, 3 New Zeland Albino rabbits, were dermally exposed to 0.5 mL of undiluted Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide. The test substance was applied on the skin (abraded or not) and the test sites were covered with an occlusive dressing for 24 hours. Those exposure conditions correspond to a worst case approach as the test guidance recommends an exposure under semi-occlusive patch and for4h. Skin irritation was assessed and scored according to the Draize scale at 24 and 72 hrs after the topical application of the test patch.  The mean individual scores calculated within 2 scoring times (24 and 72 hrs) for the unabraded skin were 0.5/1.0/1.0 for erythema and 0.5/1.0/1.0 for edema.

In an eye irritation study performed similarly to the OECD 405 guideline, 0.1 mL of undiluted Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide was instilled into the right eye of 3 Albino New Zealand Rabbits. The eyes were not washed following the instillation of the substance. Animals were then observed for 14 days for redness, chemosis and discharge of the conjonctiva, corneal opacity and iris lesion. 

Eye irritation was assessed and scored according to the Draize scale at 24, 48 and 72 hrs after the instillation of the substance and then at days 7 and 14. The mean individual score were calculated within 3 scoring times (24, 48 and 72 hrs).

The mean individual scores were 1.0/2.0/2.0 for chemosis, 0.7/1.0/1.0 for iris lesion, 2.0/2.0/2.0 for conjunctival redness, and 2.0/3.0/3.0 for corneal opacity. All of these effects were not reversible within the termination of the study (14 days) in all animals.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008 including ATP3.

Self classification:

Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is not classified skin irritation according to the Regulation (EC) 1272/2008 (CLP) and to the Directive 67/548/EEC.

Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide is classified as Eye Dam. 1 (H318: causes serious eye damage) according to the Regulation (EC) 1272/2008 (CLP) and as Xi, R41 according to the Directive 67/548/EEC as the observed ocular effects were irreversible in all treated animals.