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Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985 (published)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Guideline standards not referenced within study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

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:
Six healthy male white house rabbits (2.5 - 3.0 kg weight) were used per each of 3 test groups.

Group A: Closed application area of the sample-containing patch washed with 20 mL of purified water after 5 minutes of patch application.
Group B: Closed application area of the sample-containing patch washed with 20 mL of purified water after 1 hour of patch application.
Group C: Sample-containing patch applied for 24 hours.

Hair in the flank of each animal was shaved short, 0.5 g of the sample was spread on an adhesive tape for patch test having a diameter of 1.0 inch, and this tape was affixed to 3 points of the shaved area in a closed state. After 24 hours of skin application of the sample-containing patch to the animals in Group A through C (the adhesive tape of Group C was removed), the skin area was observed for symptoms. Follow-up observation was continued for 5 days. Erythema and crust formation and edema observed with the eye were evaluated using Draize criteria. Primary irritation after 24 hours of sample application was also evaluated.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1-cyclohexyl-1H-pyrrole-2,5-dione
EC Number:
216-630-6
EC Name:
1-cyclohexyl-1H-pyrrole-2,5-dione
Cas Number:
1631-25-0
Molecular formula:
C10H13NO2
IUPAC Name:
1-cyclohexyl-1H-pyrrole-2,5-dione
Test material form:
solid: flakes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Source: The Sponsor (Nippon Shokubai). Lot/batch No.: Not specified
- Expiration date of the lot/batch: Not specified
- Purity test date: Not specified

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: n/a
- Specific activity: n/a
- Locations of the label: n/a
- Expiration date of radiochemical substance: n/a

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Not specified
- Stability under test conditions: Not specified
- Solubility and stability of the test substance in the solvent/vehicle: Not specified
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not specified

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Not specified
- Preliminary purification step (if any): Not specified
- Final dilution of a dissolved solid, stock liquid or gel: Not specified
- Final preparation of a solid: Not specified

FORM AS APPLIED IN THE TEST (if different from that of starting material) Not specified

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable) n/a

OTHER SPECIFICS: n/a

Test animals

Species:
rabbit
Strain:
not specified
Remarks:
White house rabbits
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Medical Experimental Animals Institute
- Age at study initiation: Not specified
- Weight at study initiation: 2.5 - 3.0 kg
- Housing: One animal each was housed in stainless steel cage for house rabbits and kept in an animal room.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22ºC +/- 3ºC
- Humidity (%): 50% +/- 10%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 16 hrs dark, 8 hrs light

IN-LIFE DATES: From: To: Not specified

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Remarks:
Hair on the flank (test area) of each animal was shaved short
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): n/a

VEHICLE
- Amount(s) applied (volume or weight with unit): n/a
- Concentration (if solution): n/a
- Lot/batch no. (if required): n/a
- Purity: n/a

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): n/a
- Concentration (if solution): n/a

POSITIVE CONTROL
- Amount(s) applied (volume or weight): n/a
- Concentration (if solution): n/a
Duration of treatment / exposure:
24 hour exposure period
Observation period:
5 days obervation period
Number of animals:
6 per group, 3 groups in total
Details on study design:
TEST SITE
- Area of exposure: 1.0 inch (2.5 cm)
- % coverage: Not specified
- Type of wrap if used: Not specified

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 20 mL of distilled water on Group A and Group B
- Time after start of exposure: 5 minutes for Group A, 1 hour for Group B

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 24 hours after application, with follow-up observation continued for 5 days

SCORING SYSTEM:
- Method of calculation: Erythema and crust formation and edema observed with the eye were evaluated using Draize criteria. Primary irritation after 24 hours of sample application was also evaluated using the irritation index below.

Irritation index = (total erythema points + total edema points) / 6 (animals)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Group C
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Group C
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Group C
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Group C
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Group C
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Group C
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
Group C
Time point:
other: 5 d
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
Group C
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
Group C
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
Group C
Time point:
24/48/72 h
Score:
1.6
Max. score:
2
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
Group C
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
Group C
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 5 days
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Group A - Mild erythema was seen after 24 hours and throughout the 5-day observation period in 5 out of 6 animals. No edema was observed.
Group B - Mild erythema was seen after 24 hours in 5 out of 6 animals. Erythema showed signs of relief from Day 2 or 3. Mild edema was also seen in 3 animals but was resolved on Day 2.
Group C - After 24 hours, moderate erythema was seen in all animals. Little relief of the symptom was seen for the 5-day observation period. Mild or moderate edema also occurred. Slight relief was subsequently observed, but edema was still seen in all animals on Day 5.

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
Based on the results of the study, N-cyclohexyl maleimide is a moderate irritant.
Executive summary:

A Primary Skin Irritation Test in House Rabbits was undertaken on 6 rabbits in each of three groups (A-C). Hair in the flank of each animal was shaved short, 0.5 g of the sample was spread on an adhesive tape for patch test having a diameter of 1.0 inch, and this tape was affixed to 3 points of the shaved area in a closed state.

Group A - Mild erythema was seen after 24 hours and throughout the 5-day observation period in 5 out of 6 animals. No edema was observed.

Group B - Mild erythema was seen after 24 hours in 5 out of 6 animals. Erythema showed signs of relief from Day 2 or 3. Mild edema was also seen in 3 animals but was resolved on Day 2.

Group C - After 24 hours, moderate erythema was seen in all animals. Little relief of the symptom was seen for the 5-day observation period. Mild or moderate edema also occurred. Slight relief was subsequently observed, but edema was still seen in all animals on Day 5.

Based on the results of the study, N-cyclohexyl maleimide is a moderate irritant. If on skin, washing the skin immediately with abundant running water should reduce irritation to some extent.