Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Test animals / tissue source

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

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

 

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

Applicant's summary and conclusion

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