1,7-Naphthalenedisulfonic acid, 2-[[4-chloro-6-(cyanoamino)-1,3,5-triazin-2-yl]amino]-5-hydroxy-6-[2-[2-methoxy-5-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]diazenyl]-, lithium sodium salt (1:?:?)

Endpoint summary

Description of key information

The test substance is non irritant to skin or eyes

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:

From Jul. 06, 1999 to Oct. 14, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute 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: Charles River Deutschland GmbH, 88353 Kiβlegg
- Weight at study initiation: 2.2 - 2.6 kg
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: water from automatic water dispensers, ad libitum
- Acclimation period: 1 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 50±20 °C
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: Jul. 06, 1999 To: Jul. 13, 1999

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 g of test substance pasted with 0.5 mL deion. water

Duration of treatment / exposure:

4 h

Observation period:

24, 48 and 72 h after removal of the patches, additional readings were performed after 7 d

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: Dorsal region of the body
- % coverage: 25 cm2
- Type of wrap if used: Yes, The test substance was evenly distributed over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

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

SCORING SYSTEM: Erythema, eschar formation and edema were evaluated numerically according to the score of DRAIZE

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:

No abnormalities detected in any of the tested animals at time points till 72 h

Other effects:

No signs of irritations were observed during the whole observation period
30 - 60 min up to 72 h after decontamination the skin of two animals showed an orange discoloration. 7 d after decontamination all discoloration were disappeared.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance was considered to be non-irritating to rabbit skin

Executive summary:

A study was conducted to assess the skin irritation potential of test substance to the rabbit skin according to EU Method B.4. and OECD Guideline 404 in compliance with GLP.

Three animals were treated with 0.5 g of the test substance pasted with 0.5 mL deionised water using semi-occlusive patches for 4 h. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water. The skin was evaluated for erythema, eschar formation and edema numerically according to the score of Draize system for up to 72 h after patch removal and additionally for 7 d.

No signs of irritation were observed during the whole observation period.30 - 60 min up to 72 h after decontamination the skin of two animals showed an orange discolouration and this discolouration disappeared 7 d after decontamination.

Under the test conditions, the test substance was considered to be non-irritating to rabbit skin.

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:

weight of evidence

Study period:

From Jul. 13, 1999 to Oct. 14, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kiβlegg
- Weight at study initiation: 3.4 kg
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: water from automatic water dispensers, ad libitum
- Acclimation period: 1 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 °C
- Humidity (%): 50±20 °C
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: Jul. 13, 1999 To: Aug. 03, 1999

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

72 h. Since effects were still present in the treated eye after 72 h, further examinations were carried out after 7, 14 and 21 d.

Number of animals or in vitro replicates:

1 rabbit

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, 24 h after administration the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C
- Time after start of exposure: 24 h

SCORING SYSTEM: Lesions in cornea, iris or conjunctivae were graded numerically "Scale for scoring ocular reactions"

TOOL USED TO ASSESS SCORE: 0.01 % fluorescein-sodium solution

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritant / corrosive response data:

- 1 h up to 7 d after treatment the animal showed some definitely injected blood vessels and swelling above normal up to obvious swelling with partial eversion of lids. The irritations were attended by serous substance coloured eye discharge.
- 14 d after treatment signs of irritation were reversed.
- The nictating membrane was discolored orange from 1 h up to the end of study.

Interpretation of results:

GHS criteria not met

Conclusions:

No irritating effects were noted, but discolouration of the nictitating membranes

Executive summary:

A study was conducted to assess the eye irritation potential of test substance to the rabbit eye according to EU Method B.5. and OECD Guideline 405 in compliance with GLP.

 

One animal received 100 mg of an undiluted test substance into conjunctival sac of the left eye. The other eyes served as untreated control. 24 h after the administration the eyes were washed thoroughly with isotonic saline at 37 °C. The eyes were also washed out at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed.

 

The eyes were examined 1, 24, 48 and 72 h after administration of the test substance. At 24 and 72 hours and after 7, 14 and 21 d, the eyes were further examined for cornea/lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically (Scale for scoring ocular reactions). All other changes or toxic effects were recorded when apparent.

 

One hour up to 7 d after treatment the animal showed some definitely injected blood vessels and swelling above normal up to obvious swelling with partial eversion of lids. The irritations were attended by serous substance coloured eye discharge. 14 d after treatment signs of irritation were reversed. The nictating membrane was discolored orange from 1 h up to the end of study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

A study was conducted to assess the skin irritation potential of test substance to the rabbit skin according to OECD Guideline 404 and EU Method B.4.

Three animals were treated with 0.5 g of the test substance pasted with 0.5 mL deionised water using semi-occlusive patches for 4 h. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water. The skin was evaluated for erythema, eschar formation and edema numerically according to the score of Draize system for up to 72 h after patch removal and additionally for 7 d. No signs of irritation were observed during the whole observation period.30 - 60 min up to 72 h after decontamination the skin of two animals showed an orange discolouration and this discolouration disappeared 7 d after decontamination.

The test substance was considered to be non-irritating to rabbit skin (Dr. Seeberger A, 1999).

Based on the available in vivo skin irritation study, test substance was found to be non-irritating to skin and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).

 

Eye irritation:

A study was conducted to assess the eye irritation potential of test substance to the rabbit eye according to OECD Guideline 405 and EU Method B.5.

One animal received 100 mg of an undiluted test substance into conjunctival sac of the left eye. The other eyes served as untreated control. 24 h after the administration the eyes were washed thoroughly with isotonic saline at 37 °C. The eyes were also washed out at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed.

The eyes were examined 1, 24, 48 and 72 h after administration of the test substance. At 24 and 72 h and after 7, 14 and 21 d, the eyes were further examined for cornea/lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically (Scale for scoring ocular reactions). All other changes or toxic effects were recorded when apparent.

One hour up to 7 d after treatment the animal showed some definitely injected blood vessels and swelling above normal up to obvious swelling with partial eversion of lids. The irritations were accompanied by serous substance coloured eye discharge. 14 d after treatment signs of irritation were reversed. The nictitating membrane was discolored orange from 1 h up to the end of study. At the time the study was conducted, the permanent discolouration of the nictitating membranes led to the classification of "risk of serious damage to the rabbit eye"; consequently, the study was completed with testing one animal only. However, with the new CLP Regulation (EC) No 1907/2006, the substance has not to be classified.

As relevant information on further two animals is missing from this study, a weight of evidence approach using read-across to a structural analogue was used to assess the eye irritation potential of Reactive Orange DYPE 1466.

In this eye irritation study, 100 mg of the structural analogue was administered once to the conjunctival sac of the left eye of three rabbits. In each case the untreated eyes served as a control. From one hour up to 3 days after; application the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse deeper crimson red color and slight swelling up to partial eversion of lids. The irritations were accompanied by compound-coloured eye discharge. 7 days after application the irritations were reversed. This study showed that the structural analogue is slightly irritating to the eye. However, according to EU CLP the substance is not irritating or corrosive to eyes; hence, the test substance has not to be classified.

Justification for classification or non-classification

Skin

Based on the available in vivo skin irritation study, test substance was found to be non-irritating to skin and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).

Eye

Based on the available in vivo eye irritation study, test substance was found to be non-irritating to eyes and does not meet the requirement for classification according to CLP criteria (EC 1272/2008).