Disodium 1,1'-isopropylidenedi-p-phenylene bis[2-[[5-amino-3-methyl-1-(3-sulphonatophenyl)-1H-pyrazol-5-yl]azo]benzenesulphonate]

Endpoint summary

Description of key information

FAT 21015/A is to be considered as a non- irritant to the skin and eyes of rabbits.

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:

30 May 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

SOURCE ANIMAL
- Source: New Zealand White
- Sex: male and female
- Age at study initiation (in days): 63 - 105 days
- Weight at study initiation: 2.60 kgs (males) and 2.58 kgs (females)
- Housing: Semi-barrier system
- Die: Styles-Oxoid commercial irradiated diet ad libitum
- Water: Sterile filtered water ad libitum
- Acclimation period: 1 week

Animals:
Healthy New Zealand white rabbits (Porton strain) aged 9-15 weeks with average body weights of 2.60 Kgs. (M) and 2.58 Kgs. (F), bred on the premises and maintained under a semi-barrier system. Six rabbits (3M and 3F) were acclimatized in the test area for one week prior to the start of the trial.

Husbandry:
The rabbits were caged singly in an experimental room maintained at a temperature of 20 °C. (± 1°) and a relative humidity of 50-70 %. Animals were exposed to artificial light for 10 h daily from 08.00 - 18.00 h. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Type of coverage:

occlusive

Preparation of test site:

other: one side abraded and other side shaved only

Vehicle:

water

Controls:

no

Amount / concentration applied:

10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml; 0.75 ml of which was applied.

Dose: 0.5 g

Duration of treatment / exposure:

After 24 h the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 h. The assessment of the macroscopic skin reaction was made according to the following grading system.

Observation period:

72 h

Number of animals:

6 rabbits (3 males and 3 females)

Details on study design:

Method:
The test was carried out according to the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). Twenty-four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10 % of the total body surface. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before the application of the test compound, the right hand site was abraded with the point of a sterile hypodermic needle. The abrasions were sufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand site remained intact. 10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml, 0.75 ml of which was applied to each test site on a 2.5 c.m. square gauze pad. These were covered with aluminium foil secured with "Sleek"* adhesive tape. The test sites were then enclosed by a 6" wide "Coban" self adhesive bandage the edges of which were fixed to the skin by strips of "Sleek" in order to retain the test substance in close contact with the skin. After 24 h the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 h. The assessment of the macroscopic skin reaction was made according to the following grading system.

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

intact and abraded skin

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Remarks:

intact and abraded skin

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Individual Animal Score: Erythema

Animal Number	Intact Skin		Abraded skin
	24 h	72 h	24 h	72 h
11	0	0	0	0
13	0	0	0	0
15	0	0	1	0
12	0	0	1	0
14	1	0	1	0
16	0	0	0	0

 

Individual Animal Score: Edema

Animal Number	Intact Skin		Abraded skin
	24 h	72 h	24 h	72 h
11	1	0	2	1
13	1	0	1	0
15	1	0	2	0
12	3	0	3	1
14	1	0	2	1
16	3	0	3	1

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 21015/A is to be considered as a non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine skin irritation of FAT 21015/A in rabbits according to the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). Six animals with intact and abraded skin were used for this purpose. 10 g of the test compound was mixed uith 10 ml of water to make a solution of 15 ml, 0.75 ml of which was applied to each test site on a 2.5 cm square gauze pad (conc:0.5 g). Slight erythema and very slight to moderate oedema were seen in 3/6 and 6/6 rabbits respectively 24 h after application of the compound. Very slight oedema was still present on 4/6 abraded sites only at 72 h. The primary irritation score was 1.3. However, the substance did not warrant classification according to the CLP (Regulation 1272/2008) criteria. Hence, FAT 21015/A is to be considered as a non-irritant to the skin of rabbits.

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:

06 June 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances. Labelling Act Sect. 191.1.2 (February 1965), with slight modification.

Deviations:

not specified

Principles of method if other than guideline:

None

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals:
Healthy New Zealand White rabbits (Porton strain) aged 9-15 weeks with average body weights of 2.6.0 kgs. (M) and 2.58 kgs. (F), bred on the premises and maintained under a semi-barrier system. Six rabbits (3 M and 3 F) were acclimatised in the test area for one week prior to the start of the trial.

Husbandry:
The rabbits were caged singly in an experimental room maintained at a temperature of 20 °C. (+/- 1°) and a relative humidity of 50-70 %. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18 .00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

100 mg of the test compound were instilled into the conjunctival sac of the left eye. The right eye served as a control.

Duration of treatment / exposure:

The eyelids were then held closed for 1 second after the application of test material. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with warm water for 1 minute.

Observation period (in vivo):

The rabbits were examined 1, 24, 48 and 72 h after application of the.test compound and for any further period that was considered necessary.

Number of animals or in vitro replicates:

Six rabbits (3 males and 3 females).

Details on study design:

The test was carried out in accordance with the procedure set out in the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances. Labelling Act Sect. 191.1.2 (February 1965), with slight modification. The eyes of the experimental animals were examined and found normal prior to the test. 100 mg. of the test compound were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes- of three of the rabbits with warm water for 1 minute. The rabbits were examined 1, 24, 48 and 72 hours after application of the.test compound and for any further period that was considered necessary. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

1.8

Max. score:

3

Reversibility:

fully reversible within: 6 d

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible within: 6 d

Irritant / corrosive response data:

A very slight to moderate conjunctival reaction was noted in all treated eyes one hour after application of the compound. This had subsided slightly by 24 hours, and thereafter continued to do so slowly until all eyes were normal by day 10. A corneal reaction consisting of damage to the superficial epithelium was noted in 2/3 unwashed and 1/3 washed eyes. This was still present at 24 h in 1/3 unwashed eyes. There was very little difference in reactions between washed and unwashed eyes.

Other effects:

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 21015/A is considered to be a non-irritant to the eyes.

Executive summary:

A key study was performed to determine the eye irritation potential of FAT 21015/A in rabbits. Six rabbits were used for this purpose. A very slight to moderate conjunctival reaction was noted in all treated eyes one hour after application of the compound. This had subsided slightly by 24 hours, and thereafter continued to do so slowly until all eyes were normal by day 10. A corneal reaction consisting of damage to the superficial epithelium was noted in 2/3 unwashed and 1/3 washed eyes. This was still present at 24 h in 1/3 unwashed eyes. There was very little difference in reactions between washed and unwashed eyes. However the mean scores for corneal opacity, iris, conjuctival redness and chemosis of individual animals did not fulfill the CLP criteria for classification. Hence, FAT 21015/A is considered to be a non-irritant to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

A key study was performed to determine skin irritation of FAT 21015/A in rabbits according to the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). Six animals with intact and abraded skin were used for this purpose. 10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml 0.75 ml of which was applied to each test site on a 2.5 cm square gauze pad. Slight erythema and very slight to moderate oedema were seen in 3/6 and 6/6 rabbits respectively 24 hours after application of the compound. Very slight oedema was still present on 4/6 abraded sites only at 72 hours. The primary irritation score was 1.3. However, the substance did not warrant classification according to the CLP (Regulation 1272/2008) criteria. Hence, FAT 21015 is to be considered as a non-irritant to the skin of rabbits.

Eye Irritation:

A key study was performed to determine the eye irritation potential of FAT 21015/A in rabbits. Six rabbits were used for this purpose. A very slight to moderate conjunctival reaction was noted in all treated eyes one hour after application of the compound. This had subsided slightly by 24 hours, and thereafter continued to do so slowly until all eyes were normal by day 10. A corneal reaction consisting of damage to the superficial epithelium was noted in 2/3 unwashed and 1/3 washed eyes. This was still present at 24 hours in 1/3 unwashed eyes. There was very little difference in reactions between washed and unwashed eyes. However, the mean scores for corneal opacity, iris, conjuctival redness and chemosis of individual animals did not fulfill the CLP criteria for classification. Hence, FAT 21015 is considered to be a non-irritant to the eyes.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study Acid Yellow 079 does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 to be irritating to the skin as well as eyes.