N-[4-(aminocarbonyl)phenyl]-4-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]benzamide

Endpoint summary

Description of key information

The test material was not irritant on skin and eyes in vivo.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 08 APR 1980 to 11 APR 1980

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 ANIMAin-house breed colony
- Weight at study initiation: 1.8 -2.4 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:

physiological saline

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg pasted in 1.5 ml 0.9 % physiol. saline

Duration of treatment / exposure:

24 h

Observation period:

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

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 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:

animal: #1, #2, #4, #6 each

Time point:

other: mean of 24 and 48 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Remarks on result:

other: clipped intact

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean of 24 and 48 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: the shortened observation period of 48 h

Remarks on result:

other: clipped intact / Expected to be reversible in the course of a prolonged observation period

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: mean of 24 and 48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: clipped intact

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

Irritant / corrosive response data:

individual animal data immediately / 24 h / 48 h after removal of patch for animal #1-#6 :

erythema: 0/0/0, 0/0/0, 1/1/1,
1/0/0, 0/1/0, 0/0/0

edema: 1/0/0, 0/0/0, 1/0/0,
0/0/0, 0/0/0, 1/0/0

Effects from scarified skin were a little stronger, but in the same range.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material did not reveal any remarkable irritation potential onto the skin of rabbits under these test conditions (FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973)). 500 mg of substance were applied to the skin of six animals and skin reactions were noted for 48 h after end of exposure (exposure lasted for 24 h).Only slight effects could be observed (erythema score 1, edema score 1), 1/6 animals had still an erythema score of 1 at the end of the observation time. It can be concluded that a longer observation period would have resulted in a complete reversibility.

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 08 APR 1980 to 11 APR 1980

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: (Federal Register Vol. 38, no. 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
- Source: in-house breeding colony
- Housing: single
- Diet: ERKA 8300 (Futtermittelwerke Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg pasted in 0.4 ml 0.9 % physiol. saline

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: #1-#5 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:

conjunctivae score

Remarks:

redness

Basis:

animal #6

Time point:

other: mean of 24, 48 and 72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

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 at time point 1/7/24/48/72 h for animal #1-#6

cornea: 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: 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: 0/0/0/0/0, 1/0/0/0/0, 1/1/0/0/0,
1/0/0/0/0, 1/0/0/0/0, 1/1/1/0/0

chemosis: 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

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested 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 pasted in physiological saline 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 in 5/6 animals after 1 h, in 2/6 animals after 7 h and only in 1/6 animals at 24 h reading, the effect was was fully reversible within 48 h). No other effects could be observed in any animal.

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 material did not cause irritant effects on skin or eyes in vivo.