N,N'-1,4-phenylenebis[3-oxobutyramide]

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 study according to recent OECD TG.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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:

N,N'-1,4-phenylenebis[3-oxobutyramide]

EC Number:

246-438-8

EC Name:

N,N'-1,4-phenylenebis[3-oxobutyramide]

Cas Number:

24731-73-5

Molecular formula:

C14H16N2O4

IUPAC Name:

3-oxo-N-[4-(3-oxobutanamido)phenyl]butanamide

Details on test material:

- Name of test material (as cited in study report): Diacetessig - p - phenylendiamid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Test system: Young Adult New Zealand White Rabbit, SPF
- Rationale: Recognized by the international guidelines as the recommended test system.
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, D-88353 Kisslegg / Germany
- Number of animals per test: 3
- Age at treatment: 11 to 12 weeks (male), 11 to 14 weeks (females)
- Identification: By unique cage number and corresponding ear number.
- Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
- Allocation: Male No. 43, Female Nos. 44 and 45
- Room number: 0221 / RCC Ltd, Füllinsdorf
- Conditions: Standard Laboratory Conditions
Air-conditioned with ranges for room temperature of 17-23 °C, relative humidity of 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
- Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 35/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 34/05) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: purified water

Controls:

no

Amount / concentration applied:

0.5 g per animal of test substance (pulverized), moistened with 0.5 mL purified water before application.

Duration of treatment / exposure:

4 hours

Observation period:

Throughout 72 hours after treatment

Number of animals:

3 (1 m / 2 f)

Details on study design:

The pH of the test item was measured before the study initiation date. A formulation of a 1 % (w/w) suspension was prepared. The pH was found to be 5.
According to Commission Directive 2004/73/EC, 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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

other: animal # 43, 44, 45 each

Time point:

other: mean of 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

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

Results 2

Irritation parameter:

edema score

Basis:

other: animal # 43, 44, 45 each

Time point:

other: mean of 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

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

Any other information on results incl. tables

VIABILITY/MORTALITY/CLINICAL SIGNS

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

IRRITATION

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.

Animal Number	Sex	Evaluation Interval*	Erythema	Oedema
43	M	1 hour	0	0
44	F	1 hour	0	0
45	F	1 hour	0	0
43	M	24 hours	0	0
44	F	24 hours	0	0
45	F	24 hours	0	0
43	M	48 hours	0	0
44	F	48 hours	0	0
45	F	48 hours	0	0
43	M	72 hours	0	0
44	F	72 hours	0	0
45	F	72 hours	0	0

* Examinations were performed at the specified times after removal of the dressing.

COLORATION

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

CORROSION

Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

BODY WEIGHTS

A decrease in body weight (4.9 %) was noted in one animal during the acclimatization period.This animal recovered until the end of the observation period.

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

Body weight in grams
Animal No.	Sex	First Day of Acclimatization	Day of Treatment	Last Day of Observation
43	male	2080	2330	2334
44	female	2615	2829	2964
45	female	2666	2533	2779

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 referred classification criteria (Commission Directive 200 1/59/EC of August 2001), Diacetessig-p-phenylendiamid is considered to be "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of Diacetessig - p - phenylendiamid was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g (pulverized and moistened with 0.5 mL of purified water) 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 ofthe observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

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

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August2001), Diacetessig - p - phenylendiamid is considered to be "not irritating" to rabbit skin.