Registration Dossier

Administrative data

Description of key information

N-methylol methacrylamide showed slightly skin and eye irritating properties in animal tests. The classification according EU and GHS criteria is "not irritating".

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:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, pre-GLP but in compliance with OECD GLP principles.
Qualifier:
according to guideline
Guideline:
other: Draize protocol, published in J. Officiel de la Rep. Francaise, 21 Feb 1982
GLP compliance:
no
Remarks:
pre-GLP, but in compliance with OECD GLP principles
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nottingham Univ., School of Agriculture, Sutton Bonington, Leics., England
- Age at study initiation: approx. 12 - 16 weeks
- Weight at study initiation: mean value 22.73 - 3.04 kg
- Housing: single housing
- Diet: ad libitum, Rabbit Diet, A.W. Tindall Ltd., Holbeach, Lincolnshire, England
- Water: ad libitum, tap water
- Acclimation period: 5 days minimum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ±4°C
- Humidity (%): 53 - 60 %
- Air changes (per hr): approx. 10
- 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:
not specified
Amount / concentration applied:
undiluted, 0.5 ml
Duration of treatment / exposure:
24 hrs, thereafter removal of the test material
Observation period:
24h and 72h post application
Number of animals:
6
Details on study design:
SCORING SYSTEM according to Draize, 1959:
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 edem (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:
other: 24 and 72 hours
Score:
0.33
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
Time point:
other: 24 and 72 hours
Score:
0.17
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.

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

 1

 0

 1

 0

 animal 2

 1

 0

 0

 0

 animal 3

 0

 0

 0

 0

 animal 4

 0

 0

 0

 0

 animal 5

 1

 0

 0

 0

 animal 6

 1

 0

 1

 0

 average (single scores: animal 1-6)

 0.66

 0

 0.33

 0

 Primary irritation index I = Mean erythema score  (Erythema; 24h, 72h);  out of 4 scores

 0.33

 Primary irritation index II =  Mean oedema score (Oedema; 24h, 72h);   out of 4 scores

 0,17

 

 

 

 

 

 

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.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
N-methylol methacrylamide (approx. 60 % aqueous solution) was slightly irritating after 24 hours in a primary skin irritation study with rabbits (24/72-hour application, removal of the
test substance after 24 hours). The substance is very slightly irritating, but the effect is fully reversible after 72 hours. The classification according EU and GHS criteria is "not irritating".
Executive summary:

In a primary dermal irritation study, New Zealand White rabbits were dermally exposed (occluded, intact and scarified skin) to 0.5 ml N-methylol methacrylamide (approx. 60 % aqueous solution) for 24 hours. Thereafter, the test material was removed.

 

Animals then were observed up to 72 hours. Irritation was scored by the method of Draize et al, 1959.

The mean erythema score  was determined to be 0.33 out of 4 and the mean oedema score 0.17 out of 4

(average value of  the single scores animals no. 1-6, intact skin, 24h and 72h). 

The slightly irritating effects occurred only after 24 hours and were fully reversible after 72 hours.

Therefore, the test substance has to be classified - according to EU-GHS classification criteria - as non irritant for skin (EU-GHS-hazard category: none).

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 re-evaluated according to OECD criteria and test scores  (erythema, oedema) obtained for the scarified skin were regarded as irrelevant.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Qualifier:
according to guideline
Guideline:
other: Draize protocol, published in J. Officiel de la Rep. Francaise, 21 April 1971 and 5 June 1973
Principles of method if other than guideline:
Method: according to The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Draize J. H. 1959
GLP compliance:
no
Remarks:
pre-GLP, but in compliance with OECD GLP principles
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Rosemead Rabbits Ltd., Lea Valley, Essex
- Age at study initiation: approx. 12 - 16 weeks
- Weight at study initiation: 2.13 - 2.53 kg
- Housing: single housing
- Diet: ad libitum, Rabbit diet, A.W. Tindall Ltd, Holbeach, Lincolnshire
- Water: Tap water, ad libitum
- Acclimation period: minimum 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 ± 4.5 °C
- Humidity (%): 50 - 60 %
- Air changes (per hr): approx. 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each treated animal
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
single treatment, unrinsed
Observation period (in vivo):
up to 7 days after treatment
Number of animals or in vitro replicates:
6
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Score:
8.3
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
other: maximum individual score
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
other: maximum individual score
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days

Classification of eye irritation according EU-GHS-criteria: none

 

 

 

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, 2

0 0

0 0

0 0

0 0

0 0

-

 

 

3, 4

0 0

0 0

0 0

0 0

0 0

-

 

 

5, 6

0 0

0 0

0 0

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, 2

0  0

0  0

0 0

0 0

0 0

-

 

 

3, 4

0 0

0 0

0 0

0 0

0 0

-

 

 

5, 6

0 0

0 0

0 0

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,

2

2

1

1

1

1

0

1.33

 0.66

0

0

-

 

 

3,

4

2

2

2

2

1

1

1.66

1.66

0

0

-

 

 

5,

6

1

1

1

1

0

1

0.66

1

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,

2

1

1

1

1

0

0

0.66

0

0

0

-

 

3,

4

2

2

2

2

1

1

1.66

1.66

0

0

-

 

5,

6

1

1

1

0

0

0

0.66

0.33

0

0

-

 

 

 

 

 

 

 

 

 none

 

Classification Criteria for serious Eye Damage/Eye

Category 1

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

- Mean Draize score in 2 of 3 canimals:

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:
N-methylol methacrylamide (approx. 60 % aqueous solution) was slightly irritating in an eye irritation study with rabbits. Effects observed were redness and chemosis of the conjunctiva which were fully reversible after 7 days. The classification according EU and GHS criteria is "not irritating".
Executive summary:

In an eye irritation study according to Journal Officiel de la Republique,White rabbits were exposed to 0.1 ml N-methylol methacrylamide (approx. 60 % aqueous solution). 

Animals then were observed up to 7 days. Irritation was scored by the method of Draize et al, 1959.

Redness and Chemosis of slight to moderate grade was observed. The effects decreased after 3 days and were fully reversible after 7 days.

There was no evidence for corneal opacity or iritis.

 

Therefore, the test substance has to be classified - according to EU-GHS classification criteria - as non irritant to eyes (EU-GHS-hazard 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

SKIN: N-methylol methacrylamide (approx. 60 % aqueous solution) was slightly irritating after 24 hours in a primary skin irritation study with rabbits.

EYE: N-methylol methacrylamide (approx. 60 % aqueous solution) was slightly irritating in an eye irritation study with rabbits. Effects observed were redness and chemosis of the conjunctiva which were fully reversible after 7 days.

The classification according EU and GHS criteria is "not irritating".

The 60 % aqueous solution is the highest concentration available in commercial products.

 


Justification for selection of skin irritation / corrosion endpoint:
Reliably guideline study, pre-GLP but in compliance with OECD GLP principles. The 60 % aqueous solution is the highest concentration available in commercial products.

Justification for selection of eye irritation endpoint:
Reliable study, comparable to guideline Study well documented, meets generally accepted scientific principles, acceptable for assessment. The 60 % aqueous solution is the highest concentration available in commercial products.

Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification