Lithium 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonate

Endpoint summary

Description of key information

Eye irritation: not irritating
Skin irritation: not irritating

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Experimental study performed on the non-salified form of the substance under registration. The difference in counter-ion does not impact the study outcomes because the ecotoxicological properties are determined by the base of the substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Spolkem chovatelů z Hradce Králové.
- Weight at study initiation: 2.5 kg.
- Housing: housed individually in metal cages.
- Diet: pelleted standard commercially manufactured compound KO-16, supplied by s.p. Velaz Prague.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 50 ± 15 %
- Photoperiod: 12 hrs dark / 12 hrs light

Type of coverage:

occlusive

Preparation of test site:

other: scarified and intact shaved skin

Vehicle:

water

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g
- Application: as aqueous paste.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

Three rabbits

Details on study design:

TEST SITE
- Area of exposure: a day before the application, experimental rabbits were depilated on the left and right lateral surface (are 6 x 6) of the abdominal area; the skin of the right side was scarified.
- Type of wrap if used: gauze was covered by aluminum foil and cellulose wadding. Bandage was fixed by technical tape.

OBSERVATION TIME POINTS
Dermatological skin diagnostics was perfromed focusing on the symptoms of erythema, edema at 4, 24, 48 and 72 hours. The degree of erythema was diagnosed by visual check and palpation. Additional clinical examination was carried out at 24, 48 and 72 hours.

Irritation parameter:

erythema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Reversibility:

fully reversible within: 24 hrs

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Reversibility:

fully reversible within: 24 hrs

Remarks on result:

no indication of irritation

Animal N.	Reaction	After 4 hrs		After 24 hrs		After 48 hrs		After 72 hrs
		Inact skin	Scarified skin	Inact skin	Scarified skin	Inact skin	Scarified skin	Inact skin	Scarified skin
22	Erythema	0	0	0	0	0	0	0	0
28	Erythema	0	1	0	0	0	0	0	0
29	Erythema	0	0	0	0	0	0	0	0
22	Oedema	0	1	0	0	0	0	0	0
28	Oedema	0	0	0	0	0	0	0	0
29	Oedema	0	0	0	0	0	0	0	0

Interpretation of results:

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

Conclusions:

Not irritating

Executive summary:

Method

The skin irritation potential of the substance was determined following the testing procedures outlined into the OECD guideline 404. 0.5 g of test substance were placed on both intact and scarified skin, as aqueous paste. Three rabbits were used.

After 24 hours of exposure the bendage was removed and the reactions scored.

Result

The primary irritation score was 0

Mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals for both erythema and oedema reactions (in both intact and scarified 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Experimental study performed on the non-salified form of the substance under registration. The difference in counter-ion does not impact the study outcomes because the ecotoxicological properties are determined by the base of the substance. Reliability of the source study is 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Spolkem chovatelů z Hradce Králové.
- Weight at study initiation: 2.5 kg.
- Housing: housed individually in metal cages.
- Diet: pelleted standard commercially manufactured compound KO-16, supplied by s.p. Velaz Prague.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 50 ± 15 %
- Photoperiod: 12 hrs dark / 12 hrs light

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g
- Application: the substance was introduced in conjunctival sac. The upper and lower lids were maintained closed for few seconds, to avoid loss of the test substance.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Three rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with drinking water.
- Time after start of exposure: 24 hours.

SCORING SYSTEM:
The reactions observation was performed at 1, 24, 48 and 72 after substance application. 1 hour after the instillation of ocular reactions were assessed without flushing of the eye with drinking water. Reaction at 48 hours were scored without the usage of fluorescein.

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 1

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 1

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2

Remarks on result:

no indication of irritation

Animal N.	Time score (hrs)	Cornea		Iris	Conjunctival
		Opacity	Area		Redness	Chemosis	Discharge
22	1	0	0	0	1	0	2
	24	0	0	0	0	0	1
	48	0	0	0	0	0	0
	72	0	0	0	0	0	0
28	1	0	0	0	1	0	1
	24	0	0	0	1	0	0
	48	0	0	0	1	0	0
	72	0	0	0	0	0	0
29	1	0	0	0	2	0	1
	24	0	0	0	1	0	0
	48	0	0	0	1	0	0
	72	0	0	0	1	0	0

Interpretation of results:

other:

Conclusions:

Not irritating

Executive summary:

Method

The eye irritation potential of the substance was determined following the testing procedures outlined into the OECD guideline 405. 0.1 g of test substance were placed into conjunctival sac of three rabbits. After 24 hours of exposure the substance was removed using drinking water.

Result

The primary irritation score was 2

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

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

According to the CLP Regulation (EC 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.

Based on the available information, the substance can be considered as not skin irritating.

According to the CLP Regulation (EC 1272/2008), 3.3 serious eye damage/eye irritation section, 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.

Based on the available information, the substance can be considered as not eye irritating.

In conclusion, the substance is not classified for the eye/skin irritation, according to the CLP Regulation (EC 1272/2008).