1-cyclohexyl-1H-pyrrole-2,5-dione

Endpoint summary

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:

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

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

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

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

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)

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 April 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

other: house

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Medical Experimental Animals Institute
- Age at study initiation:
- Weight at study initiation: between 2.0 and 2.5 kg
- Housing: stainless steel cage
- Diet (e.g. ad libitum): Oriental RC-4 solid feed
- Water (e.g. ad libitum): yes
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 50 ± 10%.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): artificial lighting for 8 hours a day

IN-LIFE DATES: From: To:

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1g

Duration of treatment / exposure:

30s

Observation period (in vivo):

1, 24, 48, and 72 hours after instillation

Number of animals or in vitro replicates:

6 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 30s

SCORING SYSTEM: draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 30 - <= 40

Max. score:

40

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 30 - <= 40

Max. score:

40

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 30 - <= 40

Max. score:

40

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

60

Max. score:

60

Reversibility:

other: Examination impossible due to severe chemosis.

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

60

Max. score:

60

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Remarks on result:

other: Examination impossible due to severe chemosis.

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

fully reversible within: 4 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

not fully reversible within: 4 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

fully reversible within: 4 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

5

Max. score:

81

Reversibility:

other: Examination impossible due to severe chemosis.

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

5

Max. score:

5

Reversibility:

fully reversible within: 7 daya

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Reversibility:

other: Examination impossible due to severe chemosis.

Remarks on result:

not determinable

Remarks:

Examination impossible due to severe chemosis.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 3 - <= 4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The results of this study indicate that the effects on the eyes are not fully reversible in 21 days therefore it has been classified a Eye irritation Cat.2.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The results of this study indicate that the effects on the eyes are not fully reversible in 21 days therefore it has been classified a Eye irritation Cat.2. H319

Based on the results of the study, N-cyclohexylmaleimide is a moderate irritant; Skin irrit cat.2 H315.