Tetrasodium 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonate

Endpoint summary

Description of key information

Skin: not irritant

Eye: not irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

From December 21, 1993 to February 02, 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

The test was conducted by means of Read Across approach. The reliability of the source study report is 2. Further information was attached at section 13

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Supplier: association of breeders in Hadrce Kralovè
- Weight: 2,5 Kg (prior the application)
- Health status: checked frorm parasite and patogen microrganisms, viruses and fungi
- Housing: acclimatized cages (Velaz Praha)
- Selection: 6 animals pro cage by gender
- Identification: by number on cages door
- Diet: KO-16 (Velaz Praha),
- Water: ad libitum, according to SN 757111
- Cleaning: disinfection of cages
- Acclimatization: quarantine
- Acclimatization period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature : 20 ± 3 °C
- Humidity: 50 ± 15 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: intact and abraded

Vehicle:

water

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24, 48, 72 hours

Number of animals:

3

Details on study design:

DOSAGE PREPARATION: By Mettler AE 200
TEST SITE: Left and right side of the lateral surface of the abdominal area, located in epigastrium, mesogastrium, hypogastrium. Scarification of the area was performed. Area: 6x6 cm.
APPLICATION: Gauze, aluminum foil and cellulose wadding
DRESSING: Bandage

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1

Interpretation of results:

other: Not classified according to the CLP Principles

Conclusions:

Non irritating for the skin

Executive summary:

Method

The substance was tested for irritation to the skin in rabbit, White New Zealand strain, according to OECD 404.

0.5 grams of the substance were applied on intact and abraded skin and reactions (erhythema and edema) were observed for 72 hours.

Clinical signs were also observed and primary irritation score and the degree of dermal irritation were evaluated.

Conclusion

After 72 hours of observation the registering substance was considered non irritant for the 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:

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

Adequacy of study:

key study

Study period:

From December 21, 1993 to February 02 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

The test was conducted by means of Read Across approach. The reliability of the source study report is 2. Further information was attached at section 13

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Supplier: Velaz Praha
- Weight: 205-200 g (prior the application)
- Helth status: quality certification, checked frormparasite and patogen microrganisms, viruses and fungi
- Housing: plastic cages in polypropilene T3( Velaz Praha), ventilated and bedding with pure light wood shavings
- Selection: 6 animals pro cage by gender
- Identification: by number on cages and on tail
- Diet: Altromin 1320 (Velaz Praha), daily dose of 20 g
- Water: ad libitum, according to SN 757111
- Cleaning: disinfection of cages
- Acclimatization: quarantine
- Acclimatization period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature : 22 ± 3 °C
- Humidity: 50 ± 15 %
- Photoperiod (hrs dark / hrs light): 12/12

Controlling of temperature and humidity automatic

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 g

Observation period (in vivo):

1 hour, 24, 48, 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

DOSAGE PREPARATION
By Mettler AE 200

TEST SITE
Conjuntival sac

APPLICATION
Upper and lower eyelids, held for several seconds to prevent the loss of the substance

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Interpretation of results:

GHS criteria not met

Conclusions:

Non irritating to the eye

Executive summary:

Method

The substance was tested for irritation to the eye in rabbit, White New Zealand strain, according to OECD 405.

0.1 grams of the substance were applied to one eye and reactions (louding of the cornea surface, iris, conjunctival hyperemia, swelling) were observed for 72 hours.

Clinical signs were also observed and primary irritation score and the degree of ocular irritation were evaluated.

Conclusion

After 72 hours of observation the registering substance was considered non irritant to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

SKIN IRRITATION/CORROSION

A corrosive substance is a substance that 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 4 hour duration.

Three subcategories are provided within the corrosive category 1:

Subcategory 1A where responses are noted following up to 3 minutes exposure and up to 1 hour observation;

Subcategory 1B where responses are described following exposure between 3 minutes and 1 hour and observations up to 14 days;

Subcategory 1C where responses occur after exposures between 1 hour and 4 hours and observations up to 14 days

To classify a substance as irritant, the major criterion is that at least 2 of 3 tested animals have a mean score of ≥ 2,3 - ≤ 4,0.

Category 2:

- 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.

The substance is not classified a skin irritant because in the performed tests it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.

EYE IRRITATION

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.

Irreversible effects on the eye (Category 1):

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.

These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight. In this context, persistent lesions are considered those which are not fully reversible within an observation period of normally 21 days. Substances are also classified in Category 1 if they fulfil the criteria of corneal opacity ≥ 3 or iritis > 1,5 detected in a Draize eye test with rabbits, recognising that such severe lesions usually do not reverse within a 21-day observation period.

The substance does not meet the requirements to be classified in Category 1.

Irritating to eyes (Category 2)

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.

The substance does not meet the requirements to be classified in Category 2.