Succinimide

Endpoint summary

Description of key information

Suitable in vivo studies (OECD 404 and 405) are available to determine the potential of succinimide to induce skin irritation and eye irritation. Based on the results of these studies, the substance can be considered non-irritant to the skin and eye.

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

Study period:

2000-05-01 to 2000-09-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17 July 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted 29 December 1992

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Samples with approximately 0.5 g of the test substance (the weighed amounts of the individual doses were 497. 500 and 500 mg). were moistened with 1.0 mL deionised water

OTHER SPECIFICS:
- measurement of pH: 4.4 (1% solution in deionized water, v/v, determined with a pH-Meter)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, D-97633
- Age at study initiation: not specified
- Weight at study initiation: Animal No. 1: 2.4 kg, Animal No. 2: 2.2 kg, Animal No. 3: 2.3 kg
- Housing: Optimal hygienic conditions, individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm x 38 cm, with a wooden rest shelf, 15 x 59 cm
- Diet: Altromin 2023 diet for rabbits, ad libitum and hay-briquettes (supplied by SSNIFF, D-59494 Soest) were offered additionally as a dietary supplement
- Water: tap water from an automatical watering system, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22 °C
- Humidity (%): average of 61 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs light

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

0.5 g of the test substance were moistened with 1.0 mL deionised water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g (the weighed amounts of the individual doses were 497, 500 and 500 mg) were moistened with 1.0 mL deionised water

VEHICLE
- Amount(s) applied (volume or weight with unit): 1.0 mL deionised water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm at dorsal area of the trunk (dorsal thoracal region).
- Type of wrap if used: Samples of the test substance were spread on cellulose patches and were applied to the test sites. They were held in place by fixing them marginally with non-irritating tapes. The application sites were covered semi-occlusively by a dressing. Access by the animal to the application sites was prevented by a plastic collar.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: duration of exposure was 4 hours. At the end of the exposure period the dressing, the tapes with the patches and the collar were removed, residual test substance was removed with wet Kleenex-tissues.

SCORING SYSTEM:
The treated and the surrounding untreated skin (control area) were examined for erythema/eschar and oedema as well as for other local signs 1, 24, 48 and 72 hours after patch removal.
The skin was examined using a light source KL 1500 electronic.
Dermal irritation was described and recorded according to the scoring scheme of Draize (see in box “Any other information on materials & methods incl. tables”)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

All areas treated with the test substance and all control areas were normal before the application.
Erythema/eschar: Not observed at any observation point.
Edema: Not observed at any observation point.
For indi

Other effects:

None

                                             Table 1: Individual scoring values

	Scores for Animal No.:
	1	2	3
Erythema / Eschar: 1 h/24 h/48 h/72 h	0/0/0/0	0/0/0/0	0/0/0/0
Edema:  1 h/24 h/48 h/72 h	0/0/0/0	0/0/0/0	0/0/0/0

 

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance did not cause any adverse skin reactions in this study.

Executive summary:

In a primary dermal irritation study conducted according to guideline OECD 404, 3 female New-Zealand-White rabbits were exposed with 0.5 g succinimide in 1 mL deionised water for 4 hours. Animals then were observed for 72 hours. Irritation was scored by the method of Draize.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. All exposed skin sites were normal at each examination term.

In this study, succinimide is not a dermal irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

2000-05-01 to 2000-09-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 12 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

OTHER SPECIFICS:
- measurement of pH: 4.4 (1% solution in deionized water, v/v, determined with a pH-Meter)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, D-97633
- Age at study initiation: not specified
- Weight at study initiation: Animal No. 1: 2.4 kg, Animal No. 2: 2.4 kg, Animal No. 3: 2.5 kg
- Housing: Optimal hygienic conditions, individual caging in metal wire cages, Ehret GmbH, type KK016R, 79 cm x 59 cm x 35 cm
- Diet: Altromin 2023 diet for rabbits, ad libitum
- Water: tap water from an automatical watering system, ad libitum
- Acclimation period: 5 days (animal No. 1) and 12 days (animals No. 2 and No. 3)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 20 °C
- Humidity (%): average of 51 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs lightw

Vehicle:

water

Controls:

not required

Amount / concentration applied:

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjuctival sacs of the right eyes.
The weighed amounts of the individual doses were 97.89 and 95 mg.

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

Both eyes of the animals were examined within 24 hours before instillation and approximately 1, 24, 48 and 72 hours p.a.

Number of animals or in vitro replicates:

3 females

Details on study design:

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent loss of test substance.
The left eyes remained untreated and served as a control.
Firstly, the test substance was administered to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72-hour observation period (no corrosive effect), the test substance was administered to the other two animals subsequently.

Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a.
Additional examinations were performed 6 days after the instillation.
The whole eyes, especially the corneae, the irises and the conjunctivae were examined using an otoscope lamp. Eye irritation was scored and recorded according to the method of Draize (see in box "Any other information on materials & methods incl. tables")

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 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:

3

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 6 d

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

All untreated eyes ("control eyes") were normal at any observation time.
Cornea and Iris: Not affected
Conjunctivae, redness: All animals were affected with scores of "1" from 1 h p.a. onwards to 72 h p.a.
Conjunctivae, chemosis: All animals were affected with scores of "1" from 1 h p.a. onwards to a maximum of 24 h p.a.
For individual results see Table 1 in box "Any other information on results incl. tables".

Other effects:

None

 Table 1: Individual eye irritation scores             

							Conjunctivae
Time after instillation (p.a.)	Corneae animal No.			Irises animal No.			Redness animal No.			Chemosis animal No.
	1	2	3	1	2	3	1	2	3	1	2	3
1 h	0	0	0	0	0	0	1	1	1	1	1	1
24 h	0	0	0	0	0	0	1	1	1	0	1	0
48 h	0	0	0	0	0	0	1	1	1	0	0	0
72 h	0	0	0	0	0	0	1	1	1	0	0	0
mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0	1.0	1.0	1.0	0.0	0.3	0.0
6 d	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, the test substance succinimide is not irritating to the eyes. All observed effects on conjunctivae redness and chemosis were reversible within 6 days.

Executive summary:

In a primary eye irritation study conducted according to OECD guideline 405, 0.1 mL of succinimide was instilled into the conjunctival sac of one eye of 3 female New Zealand White rabbits. Animals then were observed of 6 days. Irritation was scored by the method of Draize. Irritant effects on cornea and iris were not observed at any observation point in any animal. Conjunctivae redness is observed in all animals as well as some injected blood vessels were observed from 1 h onwards until 72 h p.a. Very slight swelling was seen in all animals from 1 h onwards until a maximum of 24 h p.a. All effects were fully reversible within 6 days.

In this study, succinimide is not an eye irritant according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a primary dermal irritation study conducted according to guideline OECD 404, 3 female New-Zealand-White rabbits were exposed with 0.5 g succinimide in 1 mL deionised water for 4 hours. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. All exposed skin sites were normal at each examination term. In this study, succinimide is not a dermal irritant.

In a primary eye irritation study conducted according to OECD guideline 405, 0.1 mL of succinimide was instilled into the conjunctival sac of one eye of 3 female New Zealand White rabbits. Animals then were observed of 6 days. Irritation was scored by the method of Draize. Irritant effects on cornea and iris were not observed at any observation point in any animal. Conjunctivae redness is observed in all animals as well as some injected blood vessels were observed from 1 h onwards until 72 h p.a. Very slight swelling was seen in all animals from 1 h onwards until a maximum of 24 h p.a. All effects were fully reversible within 6 days. In this study, succinimide is not an eye irritant according to CLP criteria.

Justification for classification or non-classification

No classification for skin and eye irritation is warranted based on the results from suitable in vivo tests (OECD 404, 405).