4,4'-[(6-chloro-1,3,5-triazine-2,4-diyl)diimino]bis[5-hydroxy-6-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonic] acid, sodium salt

Endpoint summary

Description of key information

Reactive Red 230 was not irritating to skin or eye

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:

06 October to 09 October 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 7950 Biberach
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 2.5 - 3.3 kg
- Housing: single
- Diet: Altromin 2123 maintenance diet ad libitum and approx. 15 g hay/day
- Water: deionized chlorinated water ad libitum
- Acclimation period: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 21
- Humidity (%): 35 - 75
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 06. Oct To: 09. Oct. 1992

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

500 mg pasted with 0.3 mL of polyethylene glycol 400 (riedel-de Haen Ag, Seelze)

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: semi-occlusive

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

About 24 hours prior dermal treatment the fur of three rabbits was removed from the dorsal part of the torso with an electric hair clipper over an area of approximately 25 cm2. Only animals with intact skin were used.

500 mg of Reaktiv-Rot F-66813 FW (pasted with 0.3 mL of polyethylene glycol 400 ) was applied to each animal. The pasted test substance was spread over the whole surface of the 2.5 x 2.5 cm cellulose patch of a surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster strip was then fixed to the prepared skin and covered with a semi-occlusive bandage.

The exposure period was 4 hours. After the end of the 4 hours exposure period remnants of the still remaining test substance were removed from the skin with warm tap water.

The skin was examined 30 - 60 minutes and 24, 48 and 72 hours after removal of the plaster.

Erythema, eschar formation and edema were evaluated numerically. 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 slight eschar formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond area of exp.) 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

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:

There were no signs of skin irritations during the whole study period. However, large areas of the treated skin were red discolored during the whole course of the study.

Other effects:

Reddish discoloration at treated skin during entire observation time

Interpretation of results:

GHS criteria not met

Conclusions:

Reaktiv-Rot F-67787 is not irritating to the skin and not subject to labelling requirements

Executive summary:

Based on the results of the present rabbit primary dermal irritation study Reaktiv-Rot F-67787 is not irritating to the skin and not subject to labelling requirements according to the classification critera of the Directive 83/467/EEC and the Ordinance on Hazardous Substances.

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:

13 to 23. October 1992

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: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 7950 Biberach
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 3.1 - 3.5 kg
- Housing: single
- Diet: Altromin 2123 maintenance diet ad libitum and approx. 15 g hay/day
- Water: deionized chlorinated water ad libitum
- Acclimation period: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 21
- Humidity (%): 35 - 75
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 Oct. To: 23 Oct. 1992

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

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:

0.7

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

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 24 hours after administration the conjunctiva of the animals showed slight to obvious swelling with partial eversion of lids. Additionally, up to 48 hours after administration evident hyperaemie to diffuse deeper crimson coloured reddenings were noted.

From one hour up to 72 hours after administration the nictating membrane of the animals and the iris of one animal were discoloured red. 72 hours after administration the irritations were reversible.
Additional a clear from the substance discoloured discharge was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present study, Reaktiv-Rot F-67787 is not irritating to the eye. According to the classification criteria of Directive 83/467/EEC and the Ordinance on Hazardous Substances the test substance is not subject to labeling requirements.

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.

 

Based on the results of the present rabbit primary eye irritation studyReaktiv-Rot F-67787 is not irritating to the eye and not subject to labelling requirements.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint. In these the substance was tested for primary dermal irritation and corrosiveness. There were no signs of skin irritations during the whole study period. However, large areas of the treated skin were red discolored during the whole course of the study.

 

Eye irritation.

A single study was evaluated on this endpoint. In this the substance was tested for acute 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 72 hours. 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 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP and 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.