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Description of key information

Skin irritation in rabbits: corrosive after 3 min contact 
Eye irritation in rabbits: corrosive

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
DOT Packaging Group Classification
GLP compliance:
yes
Specific details on test material used for the study:
Purity: 99.38% active ingredient
Supplier: Rohm & Haas
Lot No. 6/4/96
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Adult male animals were obtained from Hazelton Research Animals. All animals were examined and quarentined for two weeks. Animals were housed
individually in environementally controlled rooms. At the time of dosing, animals were 19 - 30 weeks old and weighed from 2733-3484 grams.
Type of coverage:
other: semiocclusive (4h/1h) or open (3 min)
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hrs, 1 hr or 3 minutes
Observation period:
Skin irritation was evaluated at 1, 24, 48, 72 hrs and 7 and 14 days after patch removal.
Number of animals:
in total 4: 1 animal for 4 hr treatment; 3 animals each for 1 hr and 3 min treatment, resp.
Details on study design:
0.5 ml of the test subtance were applied to the clipped skin for 4 h under semi-occluded conditions to one rabbit, for 1 h under semi-occluded conditions to 2 rabbits, and for 3 minutes uncovered to 2 rabbits. After the exposure period the application sites were wiped with paper towels saturated with water or with a 1% ivory-soap solution prior to the tap water rinse and thereafter blotted dry with paper towels. Animals were observed daily for mortality and clinical signs.
Irritation parameter:
erythema score
Remarks:
3 min treatment
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: perimeter reddened & blanching; concave eschar after 14 d in one animal (another animal euthanized after 7 d)
Irritation parameter:
edema score
Remarks:
3 min treatment
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
2.17
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Remarks:
1 hr treatment
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: perimeter reddened & blanching; concave eschar after 14 days for 1 animal (another animal euthanized after 24 hrs)
Irritation parameter:
edema score
Remarks:
1 hr treatment
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: another animal euthanized after 24 days
Irritation parameter:
erythema score
Remarks:
4 hr treatment
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: exposed area blackened, perimeter reddened and concave eschar after 14 days, 1 animal for 4 hr treatment
Irritation parameter:
edema score
Remarks:
4 hr treatment
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
On all sites (4 h, 1h, 3 min exposure) skin irritation indicative of corrosivity (concave eschar formation) was observed. 
4 h exposure: erythema: 1h-14d: 4, concave eschar at day 7 and 14. Edema: 1 h: 4, 24 h: 3, 48 h: 2, 3d, 7d, 14d: 1
1 h exposure: animal 1: erythema: 4, blanching, concave eschar at day 7 and 14, edema: 1, 24 h: 3, 48, 72 h: 2, 7, 14 d: 1; animal 2: skin pulled off at 
time of patch removal, all layers of dermis destroyed.
3 min exposure: erythema: 4 both animals, all time points. blanching, concave escar from day day 2 (1 animal) or 7 (1 animal) to day 14. One animal 
was killed at day 7 when conclusive evidence of irreversible damage to the dermis was noted.
Other effects:
No mortality or clinical signs of systemic toxicity were observed during the study.

Methacrylic Acid

Skin lrritation Scores (Draize Criteria) - 3 Minutes

ERYTHEMA (maximal score 4):

Time After Patch Removal

------------------------------------------------------------------------------------------------------------------------

Animal No.       1 hr       24 hrs       48 hrs       72 hrs       7 days 1       4 days

96-27199              4e       4ef               4ef       4ef              4 def               4 def

96-27243              4f        4cf              4cd       4cd              4 cd -

---------------------------------------------------------------------------------

EDEMA (maximal score 4):

Animal No.

96-27199              3       3              2              2              1                     1

96-27243              3       3              2              1              1                            -

c. Blackened

d. Concave eschar

e. Application site perimeter: reddened

f. Application site perimeter: blanching

(-) No applicable data. Animal was euthanized after Day 7 scores when conclusive

evidence of irreversible damage to the dermis was noted.


Interpretation of results:
Category 1A (corrosive)
Conclusions:
Classification: highly corrosive (causes severe burns)
No mortality or clinical signs of systemic toxicity were observed during the study.
Executive summary:

Methacrylic acid was tested in a skin irritation/corrosion test in male rabbits for 4 hrs, 1 hr and 3 min. 3 minutes treatment caused erythema scores of 4 in 2/2 animals which wer not reversibale within 14 days and mean edema scores of 2.17 of 3 max. scores in 2/2 animals which were not fully reversible within 14 days.


Additional tests have been performed with 1h and 4hrs treatment.


No mortality or clinical signs of systemic toxicity were observed during the study.


Based on Classification: highly corrosive (causes severe burns)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Similar to Draize-method.
Guideline:
other: similar to Draize method
Principles of method if other than guideline:
other: application: 0.1 ml, 6 albino rabbits; scoring in accordance with Draize-method.
GLP compliance:
not specified
Specific details on test material used for the study:
Supplier: Rohm & Haas
Species:
rabbit
Strain:
other: Albino
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
not specified
Observation period (in vivo):
1 hr, 1 days, 2 day, 3 days, 4 days, 7 days
Number of animals or in vitro replicates:
6
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
probability of severe irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
animal: #2, #4
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
animal: #1, #3, #5, #6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
severe corneal, iridial and conjunctival effects persisting through the 7th day.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Executive summary:

In a study similar to Draize the eyes of 6 rabbits have been treated with 0.1 ml methacrylic acid. Severe irritation has been observed in all animals after 24, 48 and 72 hours which was not reversible within 7 days. Methacrylic acid is considered to be corrosive to eyes.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Similar to OECD-guideline, no GLP.
Principles of method if other than guideline:
other: modified according to Federal Hazardous Substances Labelling Act Regulation
GLP compliance:
no
Specific details on test material used for the study:
Purity not specified but typically >= 98 %
Species:
rabbit
Vehicle:
not specified
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
4 seconds
Observation period (in vivo):
10 seconds (then sacrifice)
Number of animals or in vitro replicates:
2
Details on study design:
Two animals were used. 0.1 ml of test substance was instilled into one eye of each animal. The eye was rinsed with 20 ml lukewarm water 4 seconds after instillation.
Irritation parameter:
other:
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Marked ocular injury. Despite the rinsing action, severe corneal opacity was exhibited by both animals 10 seconds following instillation. The test was terminated at this point on human grounds.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Classification: risk of serious damage to eyes
Executive summary:

The eyes of 2 New Zealand White rabbits were exposed to 0.1 ml methacrylic acid for 4 seconds and than rinsed withe lukewarm water.

Despite the rinsing action, severe corneal opacity was exhibited by both animals 10 seconds following instillation. The test was terminated at this point on humane grounds.

It is reasonable to assume that a similar degree of injury would be produced if full scale testing were tobe conducted, and that the product would be classified as a corrosive to the eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin


Undiluted Methacrylic acid causes full-depth destruction of the skin after 3 min contact. It is considered to be highly corrosive to tissues.


Dilutions if MAA in acetone and water show mild irritation at 4.8 % in a study in mice, in which dilutions of MAA were applied for 21 d in succession, while the effects are more pronounced at 9.6 % in acetone and progress to severe irritation at 19.2 % in acetone (see repeated dose section).


 


Eyes


Methacrylic acid is corrosive to rabbit eyes.


Remark: Under current guidelines the eye irritation test would have been not been performed for animal welfare reasons; however, historical study data are available and have been reported for completeness.


 


Respiratory system


In the 90 day repeated dose inhalation toxicity study there are indications that MAA vapour is irritating to the respiratory tract.

Justification for classification or non-classification

MAA is classified into hazard category Skin corr. 1A, with hazard statement H314, Causes severe skin burns and eye damage acc. to EC 1272/2008 and UN GHS.


MAA is classified into hazard category Eye damage 1, with hazard statement H318, Causes serious eye damage acc. to EC 1272/2008 and UN GHS.


MAA is classified into hazard category SOT SE3, with hazard statement H335: May cause respiratory irritation acc. to EC 1272/2008 and UN GHS.