tetrasodium 3-amino-4-{[4-({4-fluoro-6-[phenyl(2-{[2-(sulfonatooxy)ethyl]sulfonyl}ethyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-5-hydroxynaphthalene-2,7-disulfonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From September 28, 2004 to October 19, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

2004

Report date:

2004

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:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

457-630-8

EC Name:

-

Cas Number:

2138836-26-5

Molecular formula:

Hill formula: C29H23FN8Na4O16S5

IUPAC Name:

tetrasodium 3-amino-4-[(1E)-2-[4-({4-fluoro-6-[phenyl({2-[2-(sulfonatooxy)ethanesulfonyl]ethyl})amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazen-1-yl]-5-hydroxynaphthalene-2,7-disulfonate

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kißlegg
- Body weight range at treatment: 2.4 – 2.9 kg
- Housing: In fully air-conditioned rooms in separate cages arranged in a battery
- Diet: Ssnif K-H (V2333), ad libitum and hay (i.e., approximately 15 g daily)
- Water: Tap water in plastic bottles, ad libitum
- Acclimation period: 1 week under study conditions
-Animal identification: Ear tags

ENVIRONMENTAL CONDITIONS
- Temperature: 18±3°C (except short lasting deviations due to disturbances of air condition)
- Humidity: 50±20% (except short lasting deviations due to disturbances of air condition)
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: September 28, 2004 to October 19, 2004

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

deionized

Controls:

yes, concurrent no treatment

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

30-60 minutes, 24, 48, 72 h and 7 and 14 d after removal of the patches

Number of animals:

3 females

Details on study design:

ROUTE OF ADMINISTRATION: Dermal

FREQUENCY OF ADMINISTRATIONS: Single dose

PREPARATION OF THE TEST SUBSTANCE
Each animal was treated with 0.5 g (i.e., 500 mg) of test substance pasted with 0.35 mL of deionized water.

TEST PROCEDURE
An initial test was performed using one animal.

As no corrosive effects were observed in the initial test a confirmatory test with two further animals was conducted.

About 24 h before the start of the study the hair in the dorsal region of the body of the 3 rabbits was removed with an electric clipper over an area of about 25 cm². Only animals with intact skin were used.

Each animal was treated with 0.5 mg of test substance pasted with 0.35 mL deionized water. The test substance was evenly distributed over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (i.e., specially produced by Beiersdorf Aktiengesellschaft). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

The exposure period was 4 h. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water.

Examinations of the skin took place after 30 - 60 minutes as well as 24, 48 and 72 h after removal of the patches. Because of persistent discolorations by the test substance 72 h after removal of the patches, additional readings were performed after 7 and 14 d.

Erythema, eschar formation and edema were evaluated numerically according to the score of DRAIZE. All other changes of the skin were recorded.

SCORING SYSTEM:

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 eschar formation (injuries in depth) preventing
grading of erythema...........................................................................................................4
Not assessable.....................................................................................................................9
Edema
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:

30–60 minutes up to 7 or 14 d after removal of the patches the treated skin of the animals showed small or large light pink substance discolored areas. No signs of irritations were noted.

Other effects:

No clinical signs of systemic toxicity were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance was considered to be non-irritating to skin in an in vivo study with rabbits.

Executive summary:

A study was performed to assess the skin irritation potential of the test substance in female Crl:KBL(NZW)BR rabbits according to OECD Guideline 404, EPA OPPTS 870.2500 and EU Method B.4, in compliance with GLP.

500 mg of test substance pasted with 0.35 mL deionized water was evenly distributed over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area of about 25 cm² and then covered with a semi-occlusive bandage. The patch was allowed to remain in contact with the skin for 4 h. After the exposure period, all remnants of test substance were carefully removed from the skin with warm tap water. Animals were scored for irritation reactions after 30 - 60 minutes, and at 24, 48, 72 h and 7 and 14 d.

No severe signs of irritation were observed in treated animals during the whole observation period. Further, overall mean scores for dermal irritation were calculated to be 0.00 for erythema and eschar formation and 0.00 for edema formation. In addition, no clinical signs of systemic toxicity were observed.

 

Under the test conditions, the test substance was considered to be non-irritating to skin.