Disodium 7-[[2-(acetylamino)-4-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]phenyl]azo]naphthalene-1,3-disulphonate

Endpoint summary

Description of key information

Not skin irritating

Not eye irritating

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:

February from 21st to 27th, 1986

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:

adopted May 12, 1981

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland.
- Age at study initiation: 15 - 16 weeks.
- Weight at study initiation: 2.3 - 2.5 kg
- Acclimation period: 3 days.

Type of coverage:

not specified

Vehicle:

water

Controls:

yes, concurrent no treatment

Observation period:

72 hours

Number of animals:

1 male and 1 female

Details on study design:

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours.

SCORING SYSTEM
ERYTHEMA AND ESCHAR FORMATION
No enythema 0
Very slight enythema (barely perceptible) 1
Well defined enythema 2
Moderate to severe enythema 3
Sevene erythema (beet redness) to slight eschar formation (injuries in depth) 4

OEDEMA FORMATION
No edema 0
Veny sIight edema (barely perceptible) 1
Slight edema (edges of area weIl defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Sevene edema (raised more than 1 mm and extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal: 2/2

Time point:

24/48/72 h

Score:

< 2.3

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 2/2

Time point:

24/48/72 h

Score:

< 2.3

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Under the conditions of the experiment, test item was found to cause a primary irritation score of 0 when applied to intact rabbit skin. In the area of application, a hardly perceptible yeIlow discolouration of the skin was observed, which could be related to effects of the test article.
No corrosion effect has occurred on the skin at each measuring interval.

Animal N.	Reaction	1 hr	24 hrs	48 hrs	72 hrs
29 M	Erythema	0	0	0	0
30 F	Erythema	0	0	0	0
29 M	Oedema	0	0	0	0
30 F	Oedema	0	0	0	0

Interpretation of results:

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

Conclusions:

Not skin irritating

Executive summary:

The primary skin irritation potential of the substance was investigated according to OECD test guideline no. 404. The test item was moinstened with tap water, to one male and one female New Zealand White rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours.

Under the conditions of the experiment, test item was found to cause a primary irritation score of 0 when applied to intact rabbit skin. In the area of application, a hardly perceptible yeIlow discolouration of the skin was observed, which could be related to effects of the test article.

No corrosion effect has occurred on the skin at each measuring interval.

Conclusion

Mean values from gradings at 24, 48 and 72 hours were lower than 2.3 in all animals for both erythema/eschar and oedema reactions. Although two animals, instead of three, the results can be considered as sufficiently clear and probative to conclude that the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC) No 1272/2008.

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:

February from 21st to 27th, 1986

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:

adopted May 12, 1981

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland.
- Age at study initiation: 15 - 16 weeks.
- Weight at study initiation: 2.4 - 2.5 kg
- Acclimation period: 3 days.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

1 male and 1 female

Details on study design:

TOOL USED TO ASSESS SCORE: hand-slit lamp 30 SL and Varta Cliptrix diagnostic-lamp.

SCORING SYSTEM

CORNEAL IRRITATION
Opacity: degree of density (densest area used for assessment)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal Iuster), details of iris clear visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

IRIDIC IRRITATION
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

CONJUNCTIVAL IRRITATION
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
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, lid and/on nictating membranes
No swelling 0
Any swelling above normal (includes nictating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

Irritation parameter:

cornea opacity score

Basis:

animal: 2/2

Time point:

24/48/72 h

Score:

< 1

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

iris score

Basis:

animal: 2/2

Time point:

24/48/72 h

Score:

< 1

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 2/2

Time point:

24/48/72 h

Score:

< 2

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

chemosis score

Basis:

animal: 2/2

Time point:

24/48/72 h

Score:

< 2

Reversibility:

fully reversible within: 48 hrs

Irritant / corrosive response data:

Under the conditions of the experiment, test item was found to cause a primary irritation score of 1.3 when applied to rabbit eye mucosa. In the area of application, a slight, hardly perceptible yeIlowish-orange discolouration of the cornea and conjunctivae was observed, which could be related to effects of the test article.
No corrosion effect has occurred at each measuring intervals.

Animal N	Reaction	1 hr	24 hrs	48 hrs	72 hrs
15 M	Cornea opacity	0	0	0	0
16 F	Cornea opacity	0	0	1	0
15 M	Iris	0	0	0	0
16 F	Iris	0	0	0	0
15 M	Conjuntivae redness	0	1	1	0
16 F	Conjuntivae redness	1	1	1	0
15 M	Conjuntivae chemosis	2	0	0	0
16 F	Conjuntivae chemosis	1	1	0	0

Interpretation of results:

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

Conclusions:

Not eye irritating

Executive summary:

The primary eye irritation potential of the substance was investigated according to OECD test guideline no. 405. The test item was applied undiluted, to one male and one female New Zealand White rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours.

Under the conditions of the experiment, test item was found to cause a primary irritation score of 1.3 when applied to rabbit eye mucosa. In the area of application, a slight, hardly perceptible yeIlowish-orange discolouration of the cornea and conjunctivae was observed, which could be related to effects of the test article.

No corrosion effect has occurred at each measuring intervals.

Conclusion

The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for iritis, lower than 2 for both conjunctival redness and oedema, in all the tested animals.

Although two animals, instead of three, the results can be considered as sufficiently clear and probative to conclude that the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC) No 1272/2008.

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

SKIN IRRITATION

The primary skin irritation potential of the substance was investigated according to OECD test guideline no. 404. The test item was moinstened with tap water, to one male and one female New Zealand White rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours. Under the conditions of the experiment, test item was found to cause a primary irritation score of 0 when applied to intact rabbit skin. In the area of application, a hardly perceptible yeIlow discolouration of the skin was observed, which could be related to effects of the test article. No corrosion effect has occurred on the skin at each measuring interval.

In addition, the primary skin irritation potential of the substance was investigated in an old test run with 6 female rabbits. 0.5 g of test material were applied to intact and scarified skin, over an area of 25 cm². The scoring of skin reactions was performed at 24 and 72 hours. Under the conditions of the experiment, the test item was found to not cause any irritation to none of the tested animals, both for intact and scarified skin.

Since there are no details about the testing method and procedures, as well as there are no details about the composition of the tested lot, a reliability cannot be assigned.

EYE IRRITATION

The primary eye irritation potential of the substance was investigated according to OECD test guideline no. 405. The test item was applied undiluted, to one male and one female New Zealand White rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours. Under the conditions of the experiment, test item was found to cause a primary irritation score of 1.3 when applied to rabbit eye mucosa. In the area of application, a slight, hardly perceptible yeIlowish-orange discolouration of the cornea and conjunctivae was observed, which could be related to effects of the test article. No corrosion effect has occurred at each measuring intervals.

In addition, the primary eye irritation potential of the substance was also investigated in an old test, in which two experiments were run, each one using 6 rabbits. After administration, one eye was rinsed, while the other not; the scoring of eye reactions was performed at 24, 48, 72 hours and at the day 7th.

Under the conditions of the experiment, the test item was found to not cause irritation to none of the rinsed eyes of the tested animals. The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for iritis and lower than 2 for conjunctival oedema, in both the rinsed and not rinsed eyes of at least 11 out of 12 tested animals. The mean value from gradings of conjunctival redness resulted to be lower than 2 in rinsed eyes of all the animals; however, in not rinsed eyes the value resulted within 2 and 2.67 in 11 out of 12 animals and the effects were not fully recovered withing 7 days in 3 out of 12 animals.

Since there are no details about the testing method and procedures, as well as there are no details about the composition of the tested lot, a reliability cannot be assigned: the impact of possible impurity(ies) cannot be excluded; the amount of the substance administrated, as well as the form (e.g. redness due to powder irritating potential) are not known, thus possibile effects due to the substance form cannot be excluded; in addition, observation period was 7 days, instead of the 21 days indicated in the current version of the OECD standarized method, thus not sufficient for an adequate evaluation of the recovery ability.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008, 3.2 Skin corrosion/irritation section, skin irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

Mean values from gradings at 24, 48 and 72 hours were lower than 2.3 in all animals for both erythema/eschar and oedema reactions. Although two animals, instead of three, the results can be considered as sufficiently clear and probative to conclude that the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC) No 1272/2008.

According to the CLP Regulation (EC) No 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, which is not fully reversible within 21 days of application.

The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for iritis, lower than 2 for both conjunctival redness and oedema, in all the tested animals. Although two animals, instead of three, the results can be considered as sufficiently clear and probative to conclude that the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC) No 1272/2008.