Benzoic acid, 2-hydroxy-5-[[4-[[4-[[8-hydroxy-7-[[4-[(8-hydroxy-3,6-disulfo-1-naphthalenyl)azo]-2-methoxy-5-methylphenyl]azo]-3,6-disulfo-1-naphthalenyl]amino]-6-(phenylamino)-1,3,5-triazin-2-yl]amino]phenyl]azo]-, pentasodium salt

Endpoint summary

Description of key information

Non irritant to rabbit skin and 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:

From March 28 to April 6, 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 h: 3 rabbits
1 h or 3 min: 1 rabbit

Observation period:

72 h

Number of animals:

4 h: 3 rabbits
1 h or 3 min: 1 rabbit

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

OBSERVATION TIME POINTS
1, 24, 48 and 72 h

SCORING SYSTEM:
- 'Dermal toxicity' in Appraisal of the safety of chemicals in foods, drugs and cosmetics, Assoc. of food and drug offcials of the US, Draize (1959)

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Other effects:

Dark green coloured staining is observed.

Interpretation of results:

other: not classified according to the CLP Regulation (EC 1272/2008)

Conclusions:

Non irritant to the rabbit skin.

Executive summary:

Method

Skin irritation in rabbits according to OECD guideline 404. A single 4 -hour, semi occluded application (0.5 g) of test substance was administered to the intact skin of 3 rabbits; 3 -minute and 1 -hour semioccluded applications (0.5 g) of test substance were administered to the intact skin of one rabbit. Observations for erythema and oedema were done 24, 48 and 72 hours after start of exposure.

Results

No signs of erythema and oedema were noted. Dark-green coloured staining was noted.

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:

From April 10 to 19, 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Amount / concentration applied:

0.1 ml (69.3 mg)

Observation period (in vivo):

72 h

Details on study design:

REMOVAL OF TEST SUBSTANCE
- washing: no

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Other effects:

Black staining of the nictitating membrane and of the fur around the treated eye was noted.

effect	24 h			48 h			72 h
	rabbit no.
	1	2	3	1	2	3	1	2	3
cornea opacity	0	0	0	0	0	0	0	0	0
iris	0	0	0	0	0	0	0	0	0
conjunctivae redness	1	1	1	0	0	0	0	0	0
conjunctivae chemosis	0	0	0	0	0	0	0	0	0

Interpretation of results:

other: not classified according to the CLP Regulation (EC 1272/2008)

Conclusions:

Not irritant to the rabbit eye.

Executive summary:

Method

Eye irritation in rabbits according to OECD guideline 405.Test substance was applied to the non irrigated eye of 3 rabbits as single application of 0.1 ml (69.3 mg). Observations for signs of irritation on cornea, iris and conjunctivae were done 1, 24, 48 and 72 hours after instillation.

Results

Conjunctival redness was noted in all treated eyes at the 24 -hour observation. However, all treated eyes appeared normal at the 48 -hour observation. Black staining of the nictitating membrane and of the fur around the treated eye was also noted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin and eye irritation potential of the substance was evaluated based on in vivo studies.

Skin irritation

In the key study, the substance was tested for skin irritation according to OECD 404. Under test conditions, no signs of skin irritation were noted. In the area of application dark-green staining of the skin was observed in all rabbits. No acute toxicological signs were seen in animals during the test period.

Such findings were confirmed by an older study: at the 24 -hour observation time, signs of erythema and oedema were evident, which disappeared within the 72 -hour observation time.

 

Eye irritation

In the key study, the substance was tested for eye irritation/corrosion according to OECD 405. Conjuctivae redness was noted in all rabbits at the 24 -hour observation; however, all treated eyes appeared normal at the 48 -hour observation. Staining of the nictitating membrane was also noted.

Similar finding were obtained in an older study: conjunctival redness was noted in rinsed and unrinsed eyes, being more evident in unrinsed eyes. In any case, irritation signs completely disappeared within 10 days.

Justification for classification or non-classification

Skin Irritation

According to the CLP Regulation (EC 1272/2008), skin corrosion means the production of irreversible damage to the skin, and skin irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

A substance has to be classified as category 1 (corrosive) if it produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to a 4 hour duration.

 

A substance has to be classified as category 2 (irritant) if shows:

- mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

- inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

- in some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

 

Under the test condition, no signs of irritation were observed, thus no classification applied.

Eye Irritation

According to the CLP Regulation (EC 1272/2008), serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application .

Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

 

A substance has to be classified as category 1 (Irreversible effects on the eye), If, when applied to the eye of an animal, a substance produces:

- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

- at least in 2 of 3 tested animals, a positive response of:

- corneal opacity ≥ 3 and/or

- iritis > 1,5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

 

A substance has to be classified as category 2 (irritating to eye) if, when applied to the eye of an animal, a substance produces:

at least in 2 of 3 tested animals, a positive response of:

- corneal opacity ≥ 1 and/or

- iritis ≥ 1, and/or

- conjunctival redness ≥ 2 and/or

- conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

Under test conditions, irritation signs were well below the threshold of classification and disappeared within the end of the observation period. Therefore, no classification applied.