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Toxicological information

Skin irritation / corrosion

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1997

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Methacrylic acid
EC Number:
201-204-4
EC Name:
Methacrylic acid
Cas Number:
79-41-4
Molecular formula:
C4H6O2
IUPAC Name:
methacrylic acid
Test material form:
liquid
Specific details on test material used for the study:
Purity: 99.38% active ingredient
Supplier: Rohm & Haas
Lot No. 6/4/96

Test animals

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.

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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.


Applicant's summary and conclusion

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)

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