4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

EC Number:

277-874-7

EC Name:

4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

Cas Number:

74441-06-8

Molecular formula:

C14H13N3O2

IUPAC Name:

4-amino-N-(4-carbamoylphenyl)benzamide

Details on test material:

- Name of test material (as cited in study report): p-Aminobenzoylaminobenzamid TF

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test Animals:
Animals: Young Adult New Zealand White Rabbit, SPF
Breeder: Harlan France, ZI Le Malcourlet, 03800 Gannat / France
Number of Animals per Test: 3 (Animals of both sexes were used)
Age (when treated): 11 weeks (male), 13 weeks (females)
Body Weight Range (when treated): 2245 g (male), 2323 - 2400 g (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination.

Environmental Conditions:
Room temperature 20 ± 3 °C
Relative humidity between 30-70%,
Light cycle: 12 hours light and 12 hours dark
Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
Water: Community tap water from Füllinsdorf ad libitum

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

The test item was administered at 0.5 g/animal. Before application the test item was moistened with approximately 0.5 mL of purified water.

Duration of treatment / exposure:

The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water.

Observation period:

72 hours

Number of animals:

3 (1 male, 2 females)

Details on study design:

Preparation of Dose Formulations:
p-Aminobenzoylaminobenzamid TF was used as delivered by the Sponsor and was moistened with approximately 0.5 mL of purified water before application. The pH of the test item was measured before the study initiation date. A formulation of a 1% (w/w) solution in purified water was prepared. The pH was found to be 5 – 6. According to Commission Regulation (EC) No. 440/2008, B.4. and OECD Guidelines 404, a test item needs not to be tested if the pH-value is less than 2 or greater than 11.5, owing to its predictable corrosive properties.

Observations:
Viability / Mortality: Daily from acclimatization of the animals to the termination of test.
Clinical Signs (systemic): Daily from acclimatization of the animals to the termination of test.
Body Weights: At start of acclimatization, on the day of application and at termination of observation.

Observation and Scoring:
The skin reaction was assessed according to the numerical scoring system listed in the Commission Regulation (EC) No. 440/2008, B.4, at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item). Data were summarized in tabular form, showing for each individual animal the irritation scores for erythema and oedema at all measurement intervals. Any lesions were described, including the degree and nature of irritation, corrosion or any other toxic effects observed, and their reversibility.
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. According to Council Directive 67/548/EEC an animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema). According to Regulation (EC) No 1272/2008 an animal is positive when the mean score is 2.3 or greater. The test is positive for irritation when at least 2 animals are positive.

Pathology:
Necropsy: The animals were not sacrificed. No signs of irritation were observed on the treated skin following the application of the test item. For ethical reasons and in the interest of animal welfare, the animals were therefore re-used for the eye irritation study (Harlan Laboratories Study C57817) using the same test item.

Statistical Analysis:
No statistical analysis was performed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: # 94, 95, 96 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no signs of irritation (erythema) at any time

Results 2

Irritation parameter:

edema score

Basis:

animal: # 94, 95, 96 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no signs of irritation (edema) at any time

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
No abnormal findings were observed on the treated skin of any animal 72 hours after treatment, the end of the observation time.

Other effects:

No other effects reported.

Any other information on results incl. tables

Viability / Mortality:

No mortality occurred.

Clinical Signs:

No clinical signs were observed during the course of the study.

Body Weights:

The body weights of all rabbits were considered to be within the normal range of variability.

Coloration:

No staining produced by the test item of the treated skin was observed.

Corrosion:

No alterations of the treated skin were observed and no corrosive effects were evident on the treated skin.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Based upon the classification criteria according to the Commission Directive 2001/59/EC of August 2001, p-Aminobenzoylaminobenzamid TF is considered to be “not irritating” to rabbit skin.

Based upon the classification criteria according to the Regulation (EC) No. 1272/2008 of the European Parliament and of the Council of 16 December 2008, p-Aminobenzoylaminobenzamid TF is not classified with respect to skin irritation in the rabbit.

Executive summary:

The primary skin irritation potential of p-Aminobenzoylaminobenzamid TF was investigated according to OECD test guideline No. 404 and Commission Regulation (EC) No. 440/2008, B.4. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours.

The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Thus, the test item did not induce significant or irreversible damage to the skin.

Based upon the classification criteria according to the Commission Directive 2001/59/EC of August 2001, p-Aminobenzoylaminobenzamid TF is considered to be “not irritating” to rabbit skin.

Based upon the classification criteria according to the Regulation (EC) No. 1272/2008 of the European Parliament and of the Council of 16 December 2008, p-Aminobenzoylaminobenzamid TF is not classified with respect to skin irritation in the rabbit.