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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

11 July 1996 to 25 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.

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.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Sprague-Dawley CD strain rats supplied by Charles River (UK) Ltd, Margate, Kent were used. At the start of the study the males weighed 219 to 258g, and the females 204 to 221g, and were approximately ten to fourteen weeks old. After a minimum acclimatisation period of five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 19 to 24⁰C and relative humidity of 47 to 56%. 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.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

distilled

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers.

The appropriate amount of the test material, as received, was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) which had previously been moistened with distilled water. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

A group of five male and five female rats were treated with the test material

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity ½,1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days, 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.

Statistics:

Data evaluations included the relationship, if any, between the animal's exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Brown/orange-coloured staining of the treatment site was commonly noted during the study.
No signs of skin irritation were noted during the study.

Any other information on results incl. tables

Individual Dermal Reactions

Dose Level mg/kg	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	1-1 Male	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	1-2 Male	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	1-3 Male	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	1-4 Male	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	2-0 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	2-1 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	2-2 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	2-3 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA
	2-4 Female	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA	STA

0=no signs of dermal irritation

STA = brown/orange-coloured staining of test site

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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 acute dermal median lethal dose (LD50) of the test material, EVERZOL YELLOW GSP, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

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.

 

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). Study conducted in compliance with GLP and reported with a GLP certificate.

 

A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

 

There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study.

 

All animals showed expected gain in bodyweight during the study.

 

No abnormalities were noted at necropsy.

 

The acute dermal median lethal dose (LD₅₀) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.