Reaction mass of 4-[[4-(aminocarbonyl)phenyl]azo]-N-(2-ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide and 4-[[4-(aminocarbonyl)phenyl]azo]-3-hydroxy-N-(2-methoxyphenyl)naphthalene-2-carboxamide

Endpoint summary

Description of key information

Skin Effects

PR210

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. No erythema or edema were seen at any time point (score 0). The test item is not irritating under these test conditions.

Eye Effects

PR210

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. Only very slight effects were visible. After 1 h discharge was observed in 4/6 animals and conjunctivae redness in 1/6 animals. Conjunctivae redness was completely reversible within 7 h. Discharge was completely reversible within 48 h. No corneal or iridial effects were visible at any time point as well as no chemosis. 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

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 03 MAY 1976 to 06 MAY 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: FDA guideline (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973)

Deviations:

no

GLP compliance:

no

Remarks:

GLP was not compulsory at the time the study was conducted

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 to 2.0 kg
- Housing: single
- Diet: standard diet (ERKA 8300, Futtermittelwerke Robert Koch , 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 applied: 500 mg

Duration of treatment / exposure:

24 h

Observation period:

48 h after end of exposure

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm gauze patch
- Type of wrap if used: PVC foil, elastic bandage

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

SCORING SYSTEM: described in § 1500.41 in Fed. Reg. 38, No. 187, 27.09.1973, p. 27019, in accordance with OECD TG 404.
Scores were assessed 24, 48 and 72 h after start of exposure, which lasted for 24 h. For classification, the readings are stated here as immediately, 24 and 48 h after end of exposure.

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

other: clipped intact and clipped scarified

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect

Remarks on result:

other: clipped intact and clipped scarified

Irritant / corrosive response data:

Erythema score immediately after removal of the test item could not be detected due to pigment overlay, edema score was 0 for all animals.
The exact same results were obtained for scarified skin.

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. No erythema or edema were seen at any time point (score 0). The test item is not irritating under these test conditions.

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:

From 03 MAY 1976 to 06 MAY 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. Vol. 38, No. 187, p. 27019, 1973

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: single
- Diet: standard diet (ERKA 8300, Futtermittelwerke Robert Koch , Hamm. Germany), ad libitum
- Water: ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 100 mg

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with physiological saline
- Time after start of exposure: 24 h

SCORING SYSTEM: basically in accordance with OECD TG 405.
Scores were read 1, 7, 24, 48 and 72 h after test substance application.

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein at 48 and 72 h reading

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

3

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect

Irritant / corrosive response data:

- no iridial or corneal effects were visible at any time point.
- in the 1 h reading 1/6 animal showed an conjunctivae redness score of 1. This effect was completely reversible within 7 h.
- no chemosis was observed at any time point.
- discharge scores for animal #1,2,3,4,5,6 after 1 h: (0,1,1,1,0,1), after 7 h: (0,1,0,1,0,0), after 24 h: (0,0,0,1,0,0). After 48 and 72 h scores for all animals were 0.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was not irritating to eyes in all 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. Only very slight effects were visible. After 1 h discharge was observed in 4/6 animals and conjunctivae redness in 1/6 animals. Conjunctivae redness was completely reversible within 7 h. Discharge was completely reversible within 48 h. No corneal or iridial effects were visible at any time point as well as no chemosis. Therefore, it is concluded that the submission substance 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, as no adverse effects were observed.