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Description of key information

Methacrylamide is slightly irritating to skin based on results of in vivo studies. CLP criteria for skin irritaiton/corrosion are not met.

Methacrylamide is mildly irritaing to eyes based on results of in vivo studies. CLP criteria for eye irritation (Cat 2) are met.

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:
10-01-1989 - 17-01-1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted Feb 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Cited as Directive 84/449/EEC, B.4
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Analytical purity: > 98%
- Lot/batch No.: 86013
- Expiration date of the lot/batch: Jan 30, 1989
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: New Zealand White, KFM (SPF-quality) Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: male: 14 weeks, females: 15 weeks
- Weight at study initiation: male: 2.6 kg, females: 2.5 - 2.8 kg
- Housing: in stainless steel cages
- Diet (e.g. ad libitum): pelleted standard Kliba 341, Batch 41/88 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 4 days under test conditions after veterinary examination


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10 - 15 air changes
- Photoperiod (hrs dark / hrs light): 12 hr artificial fluorescent light/ 12 hr dark

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Diethylphthalate
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal


VEHICLE
- Amount(s) applied (volume or weight with unit): the test substance was applied moistened with neantine
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approximately 100 cm² (10 cm x 10 cm)
- Type of wrap if used: elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water
- Time after start of exposure: after 4 hr of application the test substance was removed


SCORING SYSTEM:
Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation (injuries in depth): 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

Maximum cumulative score: 8 (erythema score: 4 and edema score: 4)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Application area: scars
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Irritation response of all 3 animals was below 2.3 and fully reversible within 7 days. Due erythema in 1/3 animals methacrylamide is considered to be slightly irritating to skin.

Results:

Coloration

In the area of application no staining of the treated skin by pigment or coloring of the test article was observed.

Corrosion

No destruction or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the treated skin.

Body weights

The body weight gain of all rabbits was similar.

Toxic symptoms / mortality

No acute toxic symptoms were observed in the animals during the test period, and no mortality occured.

Necropsy

No necropsy was performed. All animals were killed and discarded.

Skin irritation scores

Table 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

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

2/1/1/

1/0/0/

24 h

2/1/1/ 

0/0/0/ 

48 h

2/0/1/ 

0/0/0/ 

72 h

2/0/1/ 

0/0/0/  

Average 24h, 48h, 72h

2/0.33/1/ 

0/0/0/ 

Reversibility*)

 c.

c. 

 

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

 

Interpretation of results:
GHS criteria not met
Conclusions:
Irritation response of all 3 animals was below 2.3 and fully reversible within 7 days. Due erythema in 1/3 animals methacrylamide is considered to be slightly irritating to skin.
Classification acc. EU CLP regulation 1272/2008: Not irritating to skin
Executive summary:

In a primary dermal irritation study (OECD 404) 1 male (14 weeks old) and 2 female (15 weeks old) New Zealand White rabbits were dermally exposed to 0.5 g of Methacrylamide (> 98 %) in diethylphthalate for 4 hours to 100 cm² of body surface area. Animals then were observed for 7 days. Irritation was scored by the method of EEC Council Directive 83/467/EEC, July 1983, Brussels. The study results were reevaluated acc. EU CLP regulation No 1272/2008. Irritation response of all 3 animals was below 2.3 and fully reversible within 7 days. Due erythema in 1/3 animals methacrylamide is considered to be slightly irritating to skin.

Classification acc. EU CLP regulation 1272/2008: 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
Study period:
1989-01-06 to 1989-01-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24 February, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Cited as Directive 84/449/EEC, B.5
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Analytical purity: > 98%
- Lot/batch No.: 86013
- Expiration date of the lot/batch: Jan 30, 1989
- Stability under test conditions: stable
- Storage condition of test material: no data
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White, KFM (SPF-quality) Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: male: 15 weeks, females: 16 weeks
- Weight at study initiation: male: 2.6 - 2.8 kg, females: 2.6 kg
- Housing: in stainless steel cages with an automatic cleaning and drinking system
- Diet (e.g. ad libitum): pelleted standard Kliba 341, Batch 41/88 and 42/88 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 4 days under test conditions after veterinary examination


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10 - 15 air changes
- Photoperiod (hrs dark / hrs light): 12 hr artificial fluorescent light/ 12 hr dark
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each treated animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g/animal
Duration of treatment / exposure:
7 days; not rinsed after 72 hours of application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3; 2 male and 1 female
Details on study design:
TREATMENT:
The eyes of the animals were observed 24 hours prior to test article administration.
The test article (0.1 g/animal) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the
eyeball. The lids were gently held together for about 1 sec to prevent loss of the article. The right eye remained untreated and served as the reference control.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed after 72 hours of application

SYMPTOMS:
The eyes of each animal were examined 1, 24, 48 and 72 hours and at 7 days after administartion. The irritation was assessed according to the
following scoring system.

SCORING SYSTEM:

CORNEAL IRRITATION
Opacity: degree of density (densest area for assessment)
No ulceration or opacity: 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1
Easily discernible translucent area; details of iris slightly obscured: 2
Nacrous area; no details of iris visible; size of pupil barely discernible: 3
Opaque cornea; iris not discernible through the opacity: 4

IRIDIC IRRITATION:
Normal: 0
Markedly deepened rugae, congestion, swelling moderate circumcorneal hyperaemia;
or injection; iris reactive to light : 1
Hemorrhage, gross destruction, or no reaction to light: 2

CONJUNCTIVAL IRRITATION:
Redness(refers to palpebral and bulbar conjunctivae; exluding cornea and iris)
Blood vessels normal: 0
Some blood vessels hyperaemia (injected): 1
Diffuse, crimson colour, individual vessels not easily discenible: 2
Diffuse beefy red: 3

Chemosis:
Swelling (refers to lids and/or nictating membranes)
No swelling: 0
Some swelling above normal: 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4

Maximum attainable score: 13


TOOL USED TO ASSESS SCORE: hand-slit lamp 30 SL/M (C. Zeiss AG, Zürich, Switzerland) and a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel,
Switzerland
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category 2B
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category: none
Irritation parameter:
iris score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category: none
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category: none
Irritation parameter:
conjunctivae score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category: none
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category: none
Irritation parameter:
chemosis score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: classification of eye irritation study according to OECD-GHS-criteria; Hazard category: none
Irritant / corrosive response data:
Mean Draize score of Coronal opacity was in all three animals after 72 hours. The irritation was reversible after 7 days.
In this study Methacrylamide is mildly irritating to eyes.
Other effects:
Results
TOXIC SYMPOTMES/MORTALITY
No actute toxic symtoms were observed in the animals during the test period, and no mortality occured.

IRRITATION
Methacrylamide showed a primary irritation score of 3.84 (not rinsed, selected observation times: 1, 24, 48, 72 hrs), when applied to the rabbit eye mucosa.

COLORATION
In the area of application no staining of the cornea and conjunctivae by pigment or coloring of Methacrylamide was observed.

OPACITY
Opacity was observed in the animals from 1 to 72 hours after treatment.

BODY WEIGHTS
The body weight gain of all rabbits was similar.

NECROPSY
No necropsy was performed. All animals were killed and discarded.

 

Classification of eye irritation studies according OECD-GHS-criteria

Substance: Methacryl amide                   MAA                                       CAS: 79-39-0

Internal No.: UNTER 88-054

Date/Expert: 06-12-15/Am

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

1

1

1

1

0

-

2

1

1

1

1

0

-

3

1

1

1

1

0

-

2B

 

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

1

0

0

0,33

0

-

2

0

0

0

0

0

-

3

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

2

2

0

-

2

2

2

1

1,67

0

-

3

2

2

1

1,67

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

1

1

0

0,67

0

-

2

1

0

0

0,33

0

-

3

1

0

0

0,33

0

-

             

 none


Classification:

Hazard Category

2B

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:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
According to OECD-GHS classification criteria the test substance Methacrylamide has to be classified as mildly irritating to eyes (hazard category: 2B). All observed effects were fully reversible after 7 days.
Executive summary:

In a primary eye irritation study (OECD 405) 0.1 g of > 98 % Methacrylamide was instilled into the conjunctival sac of the left eye of 2 male and 1 female New Zealand White rabbits (KFM (SPF-quality) Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland, 14 -15 weeks old, 2.6 -2.8 g body weight) for 72 hours (not rinsed). Animals were observed for 7 days. Irritation was scored according to EEC Council Directive 83/467/EEC (July 1983) and re-evalutated according OECD-GHS criteria.

Mean Draize score of corneal opacity was 1 in all three animals after 72 hours. The irritation was reversible after 7 days.

In this study Methacrylamide is mildly irritating to eyes.

OECD GHS Category: 2B

EU GHS Category: 2

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Methacrylamide is not irritating to skin. In a primary dermal irritation study (OECD 404) irritation response of all 3 animals was below 2.3 and fully reversible within 7 days.

Methacrylamide is mildly irritaing to eyes. In an eye irritation test acc. OECD 405 mean Draize score of corneal opacity was 1 in all three animals after 72 hours. The irritation was reversible after 7 days. Classification: Eye Irrit 2, H319: Causes serious eye irritation.

No data are available for respiratoroy irritation. As methacrylamide is a solid with low vapour pressure and irritaion to skin and eye are low, no respiratory irritation is expected.

Im Summary: Methacrylamide has to be classified with Eye Irrit 2, H319: Causes serious eye irritation acc. to CLP regulation (EC) No 1272/2008.

(UN-GHS Cat 2B)