Pentasodium 7-(4-(4-(5-amino-4-sulfonato-2-(4-((2-(sulfonato-ethoxy)sulfonyl)phenylazo)phenylamino)-6-chloro-1,3,5-triazin-2-yl)amino-2-ureidophenylazo)naphtalene-1,3,6-trisulfonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 November 1995 to 30 November 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: U.S. Environmental Protection Agency, Code of Federal Regulations 40, Part 798, Health Effects Testing Guidelines, Subpart E, Specific organ/Tissue toxicity, Paragraph 798.4470 "Primary dermal irritation", revised as of July 1, 1993

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

FAT 40'544/A)

IUPAC Name:

FAT 40'544/A)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Description: red powder
Batch number: Vers. Nr. TV 1
Purity/formulation: ca. 90 %
pH (1 g/l): 5 - 6
Stability of test article: stable at storage conditions
Storage conditions: At room temperature

Specific details on test material used for the study:

Identification: CIBACRON GELB TZ 4210 ROH LÖSUNG (LABORGETROCKNET) (FAT 40'544/A)
Description: Red powder
Batch number: TV.1
Purity/formulation: ca 90%
pH (1 g/L): 5-6
Stability of test article: stable at storage conditions: expiration date: Nov 2000
Storage conditions: At room temperature (ca 20 °C) away from sunlight.
Safety precautions: Gloves, goggles and face mask were sufficient to ensure personnel health and safety.

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 - CRL:KBL(NZW)BR
Source: Charles River Stolzenseeweg 32-36 D-88353 Kisslegg
Age at treatment: 13 weeks
Body weight at start of acclimatization: male : 2.2 kg, females: 2.2 - 2.4 kg
Body weight at start of treatment: 2.3 kg, females: 2.2 - 2.4 kg
Acclimatization: Five days under test conditions after health examination. Only healthy animals were used for the study.
Allocation: Male no. 28, Female nos. 29 - 30
Accommodation: Individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
Diet: Pelleted standard Kliba 341, Batchs 91/95 and 92/95 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum.
Water: Community tap water from Itingen, ad libitum.

ENVIRONMENTAL CONDITIONS
Air-conditioned with 10 - 15 air changes per hour and continuously monitored environment with target ranges for temperature of 20 ±3 °C and for relative humidity between 40 - 70 % (values above 70 % during cleaning process possible), 12 hours artificial fluorescent light (approx. 100 Lux) /12 hours dark, music during the light period

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

bi-distilled water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g/animal (left side only)

Duration of treatment / exposure:

4 hours

Observation period:

Viability/Mortality and Clinical Signs: Daily during the observation period.
Body Weights: At the start of acclimatization, on day 1 of test (application day) and at termination of observation.
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test article.

Number of animals:

1 male, 2 females

Details on study design:

Approximately 24 hours before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm). The skin of the animals was examined once, 1 day prior to test article administration. Only those animals with no signs of skin injury or irritation were used in the test.

On test day 1, 0.5 g of the test article was applied to approx. 6 sq.cm of the intact skin of the clipped area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The test article was applied in such a position as to preclude oral ingestion after removal of the dressing.
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.

No necropsy was performed in the animals euthanized at termination of observation.
All rabbits were euthanized by an intravenous injection of NARCOREN (Rhone Merieux GmbH, D-88471 Laupheim) into the ear vein at a dose of at least 1.0 ml/kg body weight (equivalent to 160 mg sodium pentobarbitone/kg body weight) and discarded.


EVALUATION OF SKIN REACTION
ERYTHEMA AND ESCHAR FORMATION
No erythema - 0
Very slight erythema (barely perceptible) - 1
Well defined erythema - 2
Moderate to severe erythema - 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) - 4

EDEMA FORMATION
No edema - 0
Very slight edema (barely perceptible) - 1
Slight edema (edges of area well defined by definite raising) - 2
Moderate edema (raised approximately 1 mm) - 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) - 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
Orange staining by the test article of the treated skin was observed.
The body weight gain of all rabbits was within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the rabbit skin.

Executive summary:

The primary skin irritation potential of the test article was investigated by topical application of 0.5 g onto 6 cm² intact dorsal skin of each of three young adult rabbits. This test was performed in accordance with OECD test guidline 404 in a GLP certified laboratory.

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 erythema and edema scores at any point were recorded to be Zero. The test article caused orange staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

In conclusion, the test substance is not be classified according to the CLP regulation (Regulation EC No. 1272/2008).