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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1976
Report date:
1976
Reference Type:
review article or handbook
Title:
Maleic Anhydride and Maleic Acid, SIDS Initial Assessment Report For SIAM 18
Author:
OECD SIDS
Year:
2004
Bibliographic source:
OECD SIDS Initial Assessment Report For SIAM 18, Paris, France, 20-23 April 2004

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:
New Zealand White rabbits were used to determine the skin irritation potential of maleic anhydride. Test substance (0.5 g) was applied to two intact skin locations on the backs of six rabbits for four hours.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Maleic anhydride
EC Number:
203-571-6
EC Name:
Maleic anhydride
Cas Number:
108-31-6
Molecular formula:
C4H2O3
IUPAC Name:
2,5-dihydrofuran-2,5-dione
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Maleic anhydride
- Physical state: white solid
Specific details on test material used for the study:
The maleic anhydride used in this study was supplied by the Chevron Chemical Company, Petrochemical Division, Industrial Chemicals, San Francisco, California. It was a white solid which was ground to a fine powder with a mortar and pestle.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: male New Zealand White rabbits
- Housing: individually housed in wire-bottom cages
- Diet: daily ration of a commercial laboratory feed (approximately 4 oz)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g


Duration of treatment / exposure:
4 hours
Observation period:
Irritation was scored at 4, 24, 48, 72 hours and after 7 days.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: the test material powder was applied to each of two separate intact sites on each rabbit.
- Type of wrap if used: After application of the material the sites were covered with a gauze patch which was secured by adhesive tape. The trunk of each animal was loosely wrapped in a plastic sheet. Paper' towels were wrapped around the plastic sheet to prevent tearing. A collar was placed on each animal to protect the wrappings during the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- 4, 24, 48, 72 hours and at 7 days

SCORING SYSTEM:
- Method of calculation: Draize scoring system (please refer to box " Any other information on materials and methods incl. tables")

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
3.66
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
3.66
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
(site 1)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
(site 2)
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Severe skin irritation was present in both treated areas of all rabbits for the entire 7-day observation period. For detailed results please refer to table 1 in box " Any other information on results incl. tables".
Other effects:
The pathological findings exhibit that eschar formation with epidermal regeneration was present in all of the sections. One section (not further specified) had an area of granulation tissue down to the muscle with some regeneration of epidermal tissue over the area.

Any other information on results incl. tables

Table 1: The skin corrrosion potential of maleic anhydride

Exposition:  4 h occlusive
    Site 1 Site 2
Animal  Reading  Erythema Edema Erythema Edema
1 4 h  4 3 4 3
2 4 h  4 4 4 4
3 4 h  4 4 4 2
4 4 h  4 4 4 4
5 4 h  2 1 2 4
6 4 h  4 2 4 2
1 24 h 4 4 4 4
2 24 h 4 4 4 4
3 24 h 4 4 2 2
4 24 h 4 4 4 4
5 24 h 4 4 4 4
6 24 h 4 4 4 4
1 48 h 4 3 4 3
2 48 h 4 4 4 4
3 48 h 4 4 4 2
4 48 h 4 4 4 4
5 48 h 4 4 4 4
6 48 h 4 4 4 4
1 72 h 4 3 4 3
2 72 h 4 4 4 4
3 72 h 4 4 4 2
4 72 h 4 4 4 4
5 72 h 4 3 4 3
6 72 h 4 4 4 2
1 7 d 4 2 4 2
2 7 d 4 4 4 4
3 7 d 4 4 4 2
4 7 d 4 4 4 4
5 7 d 4 2 4 2
6 7 d 4 4 4 4

At 24 hours, the mean Draize scores for erythema and edema for site 1 (site 2) were 4.0 (3.7) and 4.0 (3.7), respectively. At 48 hours, the mean scores for erythema and edema were 4.0 (4.0) and 3.8 (3.5), respectively. At 72 hours, the mean erythema and edema scores were 4.0 (4.0) and 3.7 (3.0), respectively. At 7 days, the mean erythema and edema scores were 4.0 (4.0) and 3.3 (3.0), respectively.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
In this study under the given conditions the test item showed corrosive effects. The test item is therefore classified as corrosive and in accordance with annex 6 of CLP regulation 1272/2008 classification as Skin Corr. 1B, H314 is warranted.
Executive summary:

In a primary dermal irritation study 6 male New Zealand white rabbits were dermally exposed to 0.5 mg of the test item maleic anhydride for 4 hours to two intact skin locations on the back under occlusive conditions. Irritation was scored at 4, 24, 48, and 72 hours and at 7 days after in accordance to Draize. Severe skin irritation was present in both treated areas of most rabbits for the entire 7-day observation period. Eschar formation with epidermal regeneration was present in all of the sections. One section (not further specified) had an area of granulation tissue down to the muscle with some regeneration of epidermal tissue over the area.

Based on the results, the test item is considered as corrosive and in accordance with ATP13 to CLP regulation 1272/2008 classification as Skin Corr. 1B, H314 is warranted.