Calcium 4,5-dichloro-2-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphonatophenyl)-1H-pyrazol-4-yl]azo]benzenesulphonate

Endpoint summary

Description of key information

Two studies in rabbits were performed to evaluate irritating or corrosive properties of the test material to skin

or eyes (OECD guideline 404 and Fed.Reg 38. No 187). Application of the test substance did not provoke skin irritation. Treatment of rabbits eyes caused slight to moderate conjuctival irritation. All reaction on skin and eyes has resolved within 8 days or were below treshold of regualtion. Therefore, the substance is considered to be non-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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

occlusive conditions, 72 h reading missing, 8-day observation period), limited data to test substance

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive conditions, 72 h reading missing

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

Type of cage: Cage made of stainless steel with wire mesh walk floors, floor area: 40 cm x 51 cm
No. of animals per cage: 1
Animal identification: Ear tattoo (= animal No.)
Room temperature: 20 - 26°C
Humidity: Conventional (about 30 - 70%)
Day/night rhythm: 12 h/12 h (6.00 - 18.00 hours/18.00 - 6.00 hours)
Bedding: No bedding in the cages; sawdust in the waste trays.
Diet: Ovator Solikanin 4 mm; Muskator-Werke Duesseldorf, FRG (about 130 g per animal per day)
Drinking water: About 250 ml per animal per day: demineralized water (Monday-Friday), tap water (weekends).
Mean weight of male animal: 2.64, of female animal 2.39 kg.
Acclimatization period: About 8 days before the beginning of the study in the skin laboratory; same housing conditions as during the study.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

50% suspension (app. 0.5 g of the test substance is applied)

Duration of treatment / exposure:

3 minutes and 4 hours

Observation period:

8 days

Number of animals:

2 (one male, one female)

Details on study design:

Clipping of the fur: At least 15 hours before the beginning of the study.
Application area: 2.5 cm x 2.5 cm
Appl. volume: The test patch (2.5 x 2.5 cm) is covered with an about 0.5 mm layer of the 50% suspension (thus about 0.5 g of the test substance is applied; because of the natural moisture of the skin, distilled water is used to prepare the suspensions so that the test can be carried out under as physiological conditions as possible).
Appl. site: Upper third of the back or flanks.
Removal of the test substance: At the end of the exposure period with Lutrol and Lutrol/water (1 :1).
Readings: 15 - 30 minutes after removal of the test patches and 24 h, 48 h, 8 d after the beginning of application.
Assessment according to J.H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

other: 3-min and 4-h application

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: 3-min and 4-h application

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

No effects were observed 8 days after the treatment.

Other effects:

No other effects.

Interpretation of results:

GHS criteria not met

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Draize test with an observation period of 8 days, limited data to test substance, source/breeder not mentioned, ages of animals not documented

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. 38, No. 187, § 1500.42, p. 27019, Sept. 27, 1973

Principles of method if other than guideline:

Draize Test

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

No. of animais per cage: 1
Room temperature: 20 - 26°C
Humidity: Conventional (about 30 - 70%)
Day/night rhythm: 12 h/12 h (6.00 - 18.00 hours/18.00 - 6.00 hours)
Diet: Ovator Solikanin 4 mm; Muskator-Werke, Düsseldorf, FRG (about 130 g per animal per day)
Drinking water: About 250 ml per animal per day: demineralized water (Monday - Friday), tap water (Saturday/Sunday).
Acclimatization period: About 8 days before the beginning of the study in the skin laboratory; same housing conditions as during the study.
Mean weight (kg) males 2.99, females 2.57

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

0.1 ml bulk volume (about 31 mg of the comminuted test substance)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

6

Details on study design:

Appl. site: Conjunctival sac of the right eyelid
Assessment: Based on J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health.
Readings: 1 h, 24 h, 48 h, 72 h, 8 d after application
Single application to the conjunctival sac of the eyelid; the substance is not washed out

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

1.17

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 8d

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: post observation period of 8d

Remarks on result:

other: shows tendency to normalize within 21d

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 8 days

Other effects:

Discharge was observed in three animals at reading 24 h (score 1), in two animals at reading 48 h (score 1) and in one animal at reading 72h (score 1). This was reversible within 8 days.

Table 1: Irritation results

Animal	Reading	Cornea Opacity	Iris	Conjunctiva		Additional findings
				Redness	Chemosis
1	24 h	0	0	1	0	-
2	24 h	0	0	2	1	-
3	24 h	0	0	1	0	-
4	24 h	0	0	2	1	-
5	24 h	0	0	1	0	-
6	24 h	0	0	2	1	-
1	48 h	0	0	1	0	-
2	48 h	0	0	1	1	-
3	48 h	0	0	1	0	-
4	48 h	0	0	1	0	-
5	48 h	0	0	1	0	-
6	48 h	0	0	2	1	-
1	72 h	0	0	1	0	-
2	72 h	0	0	0	0	-
3	72 h	0	0	0	0	-
4	72 h	0	0	1	0	-
5	72 h	0	0	1	0	-
6	72 h	0	0	2	1	-
1	8 d	0	0	0	0	-
2	8 d	0	0	0	0	-
3	8 d	0	0	0	0	-
4	8 d	0	0	1	0	-
5	8 d	0	0	0	0	-
6	8 d	0	0	1	0	-
mean animal 1	24 - 72 h	0.00	0.00	1.00	0.00
mean animal 2	24 - 72 h	0.00	0.00	1.00	0.67
mean animal 3	24 - 72 h	0.00	0.00	0.67	0.00
mean animal 4	24 - 72 h	0.00	0.00	1.33	0.33
mean animal 5	24 - 72 h	0.00	0.00	1.00	0.00
mean animal 6	24 - 72 h	0.00	0.00	2.00	1.00
mean	24 - 72 h total	0.00	0.00	1.17	0.33

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Procedure and results

Two studies were performed to evaluate irritating potential of the test material to skin or eyes.

In the first study, four rabbits (2/sex/dose) were each administered a single dermal dose of 0.5 g given as 50% suspension of the test substance (BASF SE 1981). Occlusive application of the test material to intact rabbit skin for four hours did not cause any reaction on animals skin.

In a second study, six rabbits were each administered a single ocular dose of 31 mg of the test substance and observed for eight days after instillation (BASF AG 1981c). A single instillation of the test material into the eye of the rabbit elicited slight, transient chemosis and moderate redness of conjunctiva which was not fully reversible within post observation period.

There are no data available about irritation to the respiratory system.

Discussion

Application of the test substance onto skin did not cause corrosion or irritation. Appllication into the conjunctival sac of the eye caused slight to moderate conjuctival irritation. Conjunctival irritation was not reversible within 8 day post observation period but showed tendency to normalize and the score of irritation was below the treshold of regulation.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Commission Regulation (EU) 2018/1480 of Oct 4 2018.