3,3'-[(4-{(E)-[2-bromo-4-nitro-6-(trifluoromethyl)phenyl]diazenyl}phenyl)imino]dipropanenitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 07-MAR-2000 to 18-MAY-2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guidance test with GLP compliance

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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:

other: Directive 92/69 EEC, B.4. "Acute Toxicity - Skin Irritation", July 31, 1992.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT41'029/A
Batch number: ARL 123/PP 1/99 UL
Purity: approx. 98 %
Color / Physical form: orange red to brown powder
Stability of test article: Stable under storage conditions
Expiry date: 04-NOV-2005
Stability of test article in bi-distilled water: Stable in bi-distilled water for at least 24 hours at room temperature.
Storage conditions: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST SYSTEM
Test system: New Zealand White Rabbit, SPF
Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
Number of animals: 1 male and 2 females
Age when treated: Males: 14 weeks; Females: 15 weeks
Body weight range when treated: approximately 2.7 to 3.1 kg
Acclimatization: Seven days under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
Allocation: Male No. 34; Female Nos. 35 and 36

HUSBANDRY
Conditions
Standard Laboratory Conditions:
Air-conditioned with 10-15 air changes per hour and continuously monitored environment with a range for room temperature of 22±3 °C, and for relative humidity between 30-65 %. The animals were provided with a 12-hour artificial fluorescent light, 12-hour dark cycle. Music was played during the light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with autoclaved wood (RCC Ltd, Füllinsdorf) and haysticks for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 30 /00) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
Water: Community tap water from Füllinsdorf, ad libitum.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

bi-distilled water

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Viability/Mortality: Daily from delivery of the animals to the termination of test.
Clinical signs: Daily from delivery of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.

Number of animals:

1 male and 2 females

Details on study design:

TEST ARTICLE PREPARATION
0.5 g (per animal) of FAT4T029/A was weighed as delivered by the sponsor and then moistened with bi-distilled water before application. The pH of the test article was not measured before treatment, due to the state of the test article.
TREATMENT
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.5 g of FAT41'029/A were put on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to approximately 6 cm2 of the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing (Isoelast Heftpflaster Acryl). The dressing was wrapped around the abdomen and anchored with tape. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
PATHOLOGY
No necropsy was performed in the animals sacrificed at termination of observation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

VIABILITY/MORTALITY AND CLINICAL SIGNS: No clinical signs of systemic toxicity were observed in the animals during the study and observation period, and no mortality occurred.
COLORATION: Light red staining produced by the test article of the treated skin was seen in all animals one hour after treatment.
BODY WEIGHTS: The body weight of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

FAT 41'029/A is considered to be "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of FAT 41'029/A was investigated by topical application of 0.5 g to 6 cm² 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 scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion.

The test article did not elicit any skin reactions at the application site at any of the observation times (all scores 0). The mean values from 24 to 72 hours were therefore 0 for erythema and for oedema. Light red staining produced by the test article of the treated skin was seen in all animals one hour after treatment. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Thus, FAT 41'029/A is considered to be "not irritating" to rabbit skin.