4-[[4-(aminocarbonyl)phenyl]azo]-N-(2-ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 03 MAY 1976 to 6 MAY 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: testing regime differs to some extent from today's standard methods, but conclusion on C&L is possible

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

Remarks:

GLP was not compulsory at the time the study was conducted

Test material

Test material information

Constituent 1

Reference substance name:

4-[[4-(aminocarbonyl)phenyl]azo]-N-(2-ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide

EC Number:

220-509-3

EC Name:

4-[[4-(aminocarbonyl)phenyl]azo]-N-(2-ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide

Cas Number:

2786-76-7

Molecular formula:

C26H22N4O4

IUPAC Name:

4-[(4-carbamoylphenyl)diazenyl]-N-(2-ethoxyphenyl)-3-hydroxy-2-naphthamide

Test material form:

solid: bulk

Test animals

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: individually
- Weight at study initiation: 1.5-2.0 kg
- Diet: mixed feed ERKA 8300 (Robert Koch, Hamm), ad libitum
- Water: tap water, ad libitum

Test system

Type of coverage:

occlusive

Preparation of test site:

other: two areas on one flank: one clipped one scarified respectively

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 g

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #4 and #5 each

Time point:

other: mean of 24 and 48 h after end of treatment

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Results 2

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean of 24 and 48 h after end of treatment

Score:

0.5

Max. score:

4

Reversibility:

not fully reversible within: 48 h (end of observation)

Remarks on result:

no indication of irritation

Remarks:

The test item is intensly red colored,. remaining traces might appear as "erythema"

Results 3

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: mean of 24 and 48 h after end of treatment

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 48 h (end of observation)

Remarks on result:

no indication of irritation

Remarks:

The test item is intensly red colored,. remaining traces might appear as "erythema"

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 and 48 h after end of treatment

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect

Irritant / corrosive response data:

The Erythema score could not be determined immediately after end of exposure due to pigment overlay. Animal #3 had an erythema score of 0 and 1 (24 and 48 h), Animal #6 had 1 and 1 in the 24 and 48 h reading. No erythema was observed in the other animals. No edema were observed at any time point.
Readings on the scarified skin showed comparable results.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this study the observation period was not long enough to check whether the observed effects are fully reversible. A longer observation period would have been preferable, because 2/6 animals showed an erythema score of 1 in the 48 h reading. But since severity was weak and incidence was low it can plausibly be assumed that the effects observed would have been completely reversible within a longer observation time.

The applied testing regime differs from today's standard methods in so far as 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).

Based on that, it can reasonably be concluded that the test item is not a skin irritant.

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 h after end of exposure. In animals with intact skin no edema were seen at any time point (score 0), slight erythema were seen in one animal after 24 h (score 1) and in two animals after 48 h. No erythema evaluation was possible immediately after end of exposure due to coloration of the skin. Effects on scarified skin were comparable to those observed on intact skin.