Sodium 2,4-diamino-5-(4-(2-sulfoxyethanesulfonyl)phenylazo)benzenesulfonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

21 June 1996 to 05 July 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted to recent EU test guidance in compliance with GLP and reported with a GLP certificate. Read across is applicable based on the content of sodium ions. The presence of these is determined by the pH of the isolation of the dyestuff itself. Therefore the substance to be registered is deemed to be a mixture of free acid, mono and di sodium salts. Upon comparison of the NMR-Spectra of the substance to be registered and the read across chemical it is evident that the chemical shifts as well as the integrations are the same, hence it is difficult to quantify free acid, mono and di variants. The CAS number proposed for the substance to be registered covers the sodium element. The associated free acid has a unique CAS number; this is referenced in the substance identity, as does the disodium variant, which is also referenced. e.

Cross-reference

Reason / purpose for cross-reference:

reference to other 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:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

27624-67-5

EC Number:

608-116-9

Cas Number:

27624-67-5

IUPAC Name:

27624-67-5

Details on test material:

See below

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.44 to 2.81 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 17 to 21⁰C and relative humidity of 58 to 70%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

distilled

Controls:

no

Amount / concentration applied:

500 mg, moistened with 0.5ml water.

Duration of treatment / exposure:

4 h

Observation period:

72 hours. Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.

Number of animals:

3

Details on study design:

On the day before the test each rabbit was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H, (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

other: overall 24, 48, 72h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 72 hours

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

other: overall 24, 48, 72h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 7 days

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

other: overal 24, 48, 72h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 72 hours

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

other: overall 24, 48, 72h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 48 hours

Results 5

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

other: overall 24, 48, 72h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 7 days

Results 6

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

other: overal 24, 48, 72h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 48 hours

Irritant / corrosive response data:

Very slight to well-defined erythema was noted at all treated skin sites at the 24 and 48-hour observations. Well-defined erythema persisted at one treated skin site at the 72-hour observation. No other evidence of erythema was noted.

Very slight oedema was noted at all treated skin sites one hour after patch removal with very slight to slight oedema at the 24-hour observation. Slight oedema persisted at one treated skin site at the 48-hour observation with very slight oedema at the 72-hour observation.
Moderate desquamation was noted at one treated skin site at the 7-day observation. No skin reactions were noted at ail treated skin sites at the 14 day observation

Other effects:

Orange/yellow-coloured staining was noted at all treated skin sites throughout the study. The staining prevented accurate evaluation of erythema at all treated skin sites one hour after patch removal. Erythematous reactions were evaluated as less than or equal to grade 1 redness. The staining did not affect evaluation of erythema at all treated skin sites at the 24-hour observation and at subsequent observations.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Mild erythema and oedema formation was observed up to 72 hours after test item application.. All effects besides staining of the skin were reversible within the 14-day observation period. The test item is not a skin irritant.

Executive summary:

The results are read across from the free acid form. Read across is applicable based on the content of sodium ions. The presence of these is determined by the pH of the isolation of the dyestuff itself. Therefore the substance to be registered is deemed to be a mixture of free acid, mono and di sodium salts. Upon comparison of the NMR-Spectra of the substance to be registered and the read across chemical it is evident that the chemical shifts as well as the integrations are the same, hence it is difficult to quantify free acid, mono and di variants. The CAS number proposed for the substance to be registered covers the sodium element. The associated free acid has a unique CAS number; this is referenced in the substance identity, as does the disodium variant, which is also referenced.

The study was performed to assess the irritancy potential of the test material following a single, 4-hour, semi-occluded application to the intact rabbit skin. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC. Study was conducted in compliance with GLP and reported with a GLP certificate.

 

Orange/yellow-coloured staining was noted at all treated skin sites throughout the study. The staining prevented accurate evaluation of erythema at all treated skin sites one hour after patch removal. Erythematous reactions were evaluated as less than or equal to grade 1 redness. The staining did not affect evaluation of erythema at all treated skin sites at the 24-hour observation and at subsequent observations.

 

Very slight to well-defined erythema was noted at all treated skin sites at the 24 and 48-hour observations. Well-defined erythema persisted at one treated skin site at the 72-hour observation. No other evidence of erythema was noted.

 

Very slight oedema was noted at all treated skin sites one hour after patch removal with very slight to slight oedema at the 24-hour observation. Slight oedema persisted at one treated skin site at the 48-hour observation with very slight oedema at the 72-hour observation.

No skin reactions were noted at all treated skin sites at the 14-day observation.

The test material did not meet the criteria for classification as irritant or corrosive. No symbol and risk phrase are required.