disodium 7-(4,6-difluoropyrimidin-2-ylamino)-4-hydroxy-3-(4-methoxy-2-sulfonatophenylazo)naphthalene-2-sulfonate; reaction mass of: disodium 7-(2,4-difluoropyrimidin-6-ylamino)-4-hydroxy-3-(4-methoxy-2-sulfonatophenylazo)naphthalene-2-sulfonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Delivery of the animals October 23, 1996 - Euthanasia of the animals October 31, 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)

Version / remarks:

adopted July 17, 1992 (reported Paris April 29, 1993)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 31, 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

426-840-1

EC Name:

-

IUPAC Name:

tetrasodium 7-[(2,6-difluoropyrimidin-4-yl)amino]-4-hydroxy-3-[2-(4-methoxy-2-sulfophenyl)diazen-1-yl]naphthalene-2-sulfonate 7-[(4,6-difluoropyrimidin-2-yl)amino]-4-hydroxy-3-[2-(4-methoxy-2-sulfophenyl)diazen-1-yl]naphthalene-2-sulfonate

Test material form:

solid

Details on test material:

Identity: Scarlet RN 1165
Appearance : Solid powder, dark-red

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Chbb: NZW (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH; Birkendorferstrasse 65; D - 88397 Biberach / Riss
- Age at treatment : 15 weeks
- Weight at study initiation:
at start of acclimatization : male 2.5 kg, females 2.5-2.6 kg
at start of treatment : male 2.7 kg, females 2.3-2.6 kg
- Housing: Individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet (batch 70/96) ad libitum from Kliba Muhlen AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are included in this report.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum. Results of bacteriological, chemical and contaminant analyses are included in this report.
- Acclimation period: Four days under test conditions after health examination. Only healthy animals were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): between 40-70% (values above 70% during cleaning process possible)
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light/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:

not specified

Amount / concentration applied:

TEST MATERIAL
Amount(s) applied (volume or weight with unit): 0.5g test item/animal (left side only)

VEHICLE
The test article was moistened with bi-distilled water before application

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after removal of the dressing

Number of animals:

3 young adults: 1 male (#1) and 2 females (#2, #3)

Details on study design:

TEST SITE
- Area of exposure: 0.5 g of the test article was applied to approx. 6 cm2 of the intact skin of the clipped area
- % coverage: It was covered with a 2.5 cm x 2.5 cm patch of surgical gauze
- Type of wrap if used: The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 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
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): h, 24h, 48h and 72 h after removal of the dressing

SCORING SYSTEM:
- Method of calculation: To classify the irritating potential of the test article, the mean values of erythema I eschar as well as of edema formation were calculated for each individual, using the scores between 24 and 72 hours (EEC Commission Directive 93/21/EEC, April 27, 1993).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

other: Animal : #1 (M), #2 (F) & #3 (F)

Time point:

other: 1h, 24h, 48h & 72h

Score:

0

Max. score:

0

Reversibility:

other: not relevant in absence of effects

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

other: Animal #1 (M), #2 (F) & #3 (F)

Time point:

other: 1h , 24h, 48h & 72h

Score:

0

Max. score:

0

Reversibility:

other: not relevant in absence of effects

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

IRRITATION
SCARLET RN 1165 showed a primary irritation score of 0.00, when applied to healthy intact rabbit skin.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.

CORROSION
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 test and observation period, and no mortality occurred.

COLORATION
Irreversible pale red staining by the test article of the treated skin was observed.

BODY WEIGHTS
The body weight gain of all rabbits was within the normal range of variability.Please refer to results in section "any other information on results incl. tables" hereafter.

Any other information on results incl. tables

Evolution of body weights in grams:

Animal#	Sex	First Day of Acclimatization	Day of Treatment	Last Day of Observation
1	Male	2540g	2675g	2748g
2	female	2469g	2349g	2577g
3	female	2360g	2551g	2664g

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (EEC Commission Directive 93/21/EEC of April 27, 1993), with the exception of the irreversible pale red staining which persisted in all animals up to termination of the test, SCARLET RN 1165 is considered to be "not irritating" to 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 New Zealand rabbits. The scoring of skin reactions was performed l, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the fol lowing reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of figures. Under the conditions of this experiment, SCARLET RN 1165 was found to cause a primary irritation score of 0.00 (max. 8.0) when applied to healthy intact rabbit skin.

Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.

The test article caused irreversible pale red staining of the treated skin.

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