5-[[4-chloro-6-[(3-sulphophenyl)amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonic acid, sodium salt

Endpoint summary

Description of key information

No irritating effects

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29. Oct to 01 Nov. 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Federal Register 38, No 187

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

FDA Federal Register 38, No 187, Patch-Test, occusive scarifized and intact skin

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

SPF Himalayan Albino Rabbits: Hoe:HIMK(SPFWiga)
Source: Hoechst AG
Food: ERKA 8300
Supplier: Futtermittelwerke Robert Koch oHG Hamm
Water: Tap water
Food and water ad libitum
Single housing
Weight: 1.5 to 2 kg

In-life date: 29. Oct to 01 Nov. 1979

Type of coverage:

occlusive

Preparation of test site:

other: abraded (3x3 cm) and shaved (3x3 cm) skin

Vehicle:

other: PEG 400 to form a paste

Controls:

yes, concurrent no treatment

Amount / concentration applied:

500 mg on 2.5 cmx2.5 cm gauze pads

Duration of treatment / exposure:

24 hours

Observation period:

up to 72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure shaved and scarified skin: 2.5x2.5 cm
- Area of exposure shaved skin: 2.5x2.5 cm
- Type of wrap if used: 6 to 8 cm wide PVC sheeting covered by elastic bandage


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours


SCORING SYSTEM: FDA Federal Register 38, No 187

Erythema and eschar formation (EEF) :
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 (EF):
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 exp.) 4

Mean value of 6 animals

Primary Irritation Index (PII) = EEF24h-abraded + EEF72h-abraded + EEF24h-shaved + EEF72h-shaved + EF24h-abraded + EF72h-abraded + EF24h-shaved + EF72h-shaved / 4

EVALUATION:

0.0 - 0.5 non-irritant
0.6 - 3.0 slightly irritant
3.1 - 5.0 moderately irritant
5.1 - 8.0 severely irritant

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

24/48/72 h

Score:

0.06

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24+72 h

Score:

0.3

Max. score:

8

Reversibility:

fully reversible

Irritant / corrosive response data:

NAD

Other effects:

-

Interpretation of results:

GHS criteria not met

Conclusions:

EU Classification: not irritating
FDA evaluation: not irritating

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 Dec. 1998 - 05 Jan. 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kißlegg
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 3.1 - 3.7 kg
- Housing: single
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: tap water from automatic water dispensers, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08 Dec. 1998 To: 05 Jan. 1999

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm physiological saline solution
- Time after start of exposure: 24 hours

SCORING SYSTEM:
1, 24, 48, and 72 hours, then at 1 week post treatment

About 24 hours before the start of the study the eyes of all animals to be treated were examined under UV light for possible corneal lesions after instillation of one drop of a 0.01 % fluorescine-sodium solution. Only animals without ocular abnormalities were used for the study.
Every 100 mg Reaktiv-Rot F-66 813 FW was administered once into the conjunctival sac of the left eye of three rabbits. In each case, the untreated eye served as a control. 24 hours after the administration of the test substance and also at the designated examination times at which the treated eyes still showed discharge, or a corneal examination with fluorescine-sodium solution was performed the treated eyes were washed thoroughly with isotonic saline (approx. 37° C).

The eyes were examined 1, 24, 48 and 72 hours after administration of the test substance. After 24 and 72 hours the cornea was additionally examined under UV-light for corneal lesions after instillation of one drop of a fluorescine-sodium solution (0.01 %). Lesions in cornea, iris and conjunctivae were graded numerically. All other changes were recorded.


1. Conjunctivae

Redness: lids and/or nictitating membranes
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis: lids and/or nictitating membranes
No swelling 0
Any amount different from normal (includes nictating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4


2. Iris
Normal 0
Markedly deepened rugae, congestion, swelling, slight
circumcorneal hyperaemia: or injection: iris still reacting to light
(a sluggish reaction is positive) 1
Haemorrhage, gross destruction, or no reaction to light. 2


3. Cornea

Opacity-degree of density (area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight
dulling of normal lustre): details of iris clearly visible 1
Easily discernible translucent area: details of iris slightly obscured 2
Nacrous area: no details of iris visible: size of pupil barely discernible 3
Opaque cornea: iris not discernible through the opacity 4

Affected area (opacity or stained by fluorescine test)
No translucense 0
Punctiform to one quarter 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4


TOOL USED TO ASSESS SCORE: fluorescein staining and UV-light 24 and 72 hours after treatment

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritant / corrosive response data:

From one hour up to 2 days after application the conjunctiva of two animals showed blood vessels definitely injected above normal up to diffuse deeper crimson red colors and swelling with partial eversion of lids.
From one hour up to 3 days after application the conjunctiva of one animal showed diffuse deeper crimson red colors up to beefy red colors and swelling with partial eversion of lids. Additionally bleeding of nictating membrane was observed.
The irritations were attended by clear substance coloured eye discharge.
7 days after application the irritations were reversible.
The iris was discolored by compound from one day up to seven days in one animal.
Additionally the nictating membrane and the conjunctivae were discolored up to the end of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present study, Reactive Red 198 is not irritating to the eye.

Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single administration of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling.

 

The present study was conducted according to EC-Guideline B.5. Acute Toxicity Eye Irritation of Directive 84/449/EEC: Commission Directive of April 25,1984 adapting for the sixth time Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of hazardous substances to the technical progressand meets the requirements of OECD Guideline for Testing of Chemicals, 405 "Acute Eye Irritation / Corrosion", OECD 1981.Updated Guideline, adopted : 24th February 1987. Study conducted in compliance with GLP.

 

Testing of Remazol Rot RB gran 133% for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / Corrosion.

The substance was tested for primary dermal irritation and corrosiveness. No inflammatory signs (eschar or oedema formation) became apparent within the observation period. Signs of toxicity were not observed. This evidence indicates no hazard potential to the skin and the test substance may therefore be regarded as 'not irritating to the skin’. It is not a dermal corrosive. No risk phrase or classification is required.

 

Eye irritation.

The substance was tested for acute eye irritation and was found not to be an irritant to the rabbit eye. Effects were noted in all animals assessed; however these were fully reversible within the observation period. No classification is applicable.

 

Respiratory irritation

Respiratory irritation was not assessed; however no effects on the animals were noted in any associated studies.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 or 2 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP an in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for irritation effects is therefore required.