N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-2-[(4-nitrophenyl)azo]-3-oxobutyramide

Endpoint summary

Description of key information

The test material is not irritating to skin.

Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.

The test material did not show remarkable irritating potential to the eyes of animals under test conditions which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the submission substance is not irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 SEP 1976 to 23 SEP 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: FDA guideline (minor deviations from OECD guideline)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: FDA guideline (Federal register 38, No. 187, 27.9.1973, p.27019)

Deviations:

no

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 - 2.0 kg
- Housing: single
- Diet: ERKA 8300 (Futtermittelwerke Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: clipped intact and clipped scarified

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

Duration of treatment / exposure:

24 h

Observation period:

48 h after removal of patch with observation time points immediately, 24 h and 48 h after removal of the patch.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: erythema and edema scores (0-4)

Skin was evaluated immediately, 24 h and 48 h after removal of the patch. Mean values of the readings 24 and 48 h after removal are reported in the results table.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 and 48 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Remarks on result:

other: clipped intact and clipped scarified

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 and 48 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Remarks on result:

other: clipped intact and clipped scarified

Irritant / corrosive response data:

Immediately after removal of patch no erythema score could be determined due to pigment overlay. Edema score at this time point was 0 for all animals. No edema or eryhthema were seen 24 and 48 h after removal of the patch (score 0).
Results on scarified skin showed identical results.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not irritating to skin under these test conditions.
This conclusion is legitimate even though the applied testing regime differs from today's standard methods. Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.

Executive summary:

The test material was tested for skin irritancy according to FDA guidelines. Both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance for 24 h under occlusive conditions and the skin responses were watched for 48 hours after end of exposure. Immediately after removal of patch no erythema score could be determined due to pigment overlay. No erythema were seen at the later observation time points. No edema were seen at any time point (score 0). The test item is not irritating under these test conditions.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 SEP 1976 to 23 SEP 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: FDA guideline, similar to OECD 405.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: FDA guideline (Federal Register Vol. 38, nr. 187, p. 27019, 1973)

Deviations:

no

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 - 2.0 kg
- Housing: single
- Diet: ERKA 8300 (Futtermittelwerke Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

24 h after exposure eyes were washed with physiological saline.

Observation period (in vivo):

72 h with observation time points at 1, 7, 24, 48 and 72 h after application.

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize Scale.

TOOL USED TO ASSESS SCORE: loupe / fluorescein (at 48 and 72 h reading)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not relevant since no effect

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #2, #5 and #6 each

Time point:

other: mean of 24, 48 and 72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #1, #3 and #4 each

Time point:

other: mean of 24, 48 and 72 h

Score:

0

Max. score:

3

Reversibility:

other: not relevant since no effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Irritant / corrosive response data:

Individual animal data for animal #1, #2, #3, #4, #5, #6 at time point 1h / 7h / 24h / 48h / 72 h

cornea score: 0/0/0/0/0 0/0/0/0/0 0/0/0/0/0
0/0/0/0/0 0/0/0/0/0 0/0/0/0/0

iris score: 0/0/0/0/0 0/0/0/0/0 0/0/0/0/0
0/0/0/0/0 0/0/0/0/0 0/0/0/0/0

conjunctivae redness: 1/1/0/0/0 1/1/1/0/0 2/1/0/0/0
1/1/0/0/0 2/1/1/0/0 1/1/1/0/0

chemosis: 0/0/0/0/0 1/0/0/0/0 1/0/0/0/0
1/0/0/0/0 1/0/0/0/0 1/0/0/0/0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material did not show remarkable irritating potential to the eyes of animals under test conditions which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. Therefore, it is concluded that the submission substance is not irritating to eyes.

Executive summary:

Test material was subject to a test of eye irritancy according to FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973). 100 mg of substance were applied to one eye of six animals each. The eyes were washed 24 h after application and eye responses were noted for 72 h after start of the exposure. Only slight effects could be observed (conjunctiva redness score of 1 or 2 one hour after application in all animals, the effect was fully reversible within 48 h; iris score = 0 at all readings; cornea score = 1 in 2 out of 6 animals one hour after application, but effect fully reversible with 7 hours; Chemosis score = 1 in 5/6 animals one hour after application, effect fully reversible within 7 hours). Overall the effects seen were minimal and it is concluded that the test material is not irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification

The test item did not cause irritation on skin and eyes in vivo.