Sodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzenesulphonato(4-)]chromate(1-)

Endpoint summary

Description of key information

Taking data from both skin and eye irritation/corrosion studies into account, it can be concluded that the test substance FAT 20043 is non-irritating to skin and eye.

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: 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).

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-13 weeks
- Weight at study initiation: average body weights of 2.73 Kgs. (males) and 2.38 Kgs. (females)
- Housing:The rabbits were caged singly in an experimental room.
- Diet: A commercial irradiated diet (Styles-Oxoid) was fed ad libitum.
- Water: Sterile filtered water was available at all times.
- Acclimation period: Six rabbits were acclimatized in the test area for one week prior to the start of the trial.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light):Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours.

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 g of the test compound was mixed with 12 ml. of water to make a solution of 15ml. 0.75ml. of which was applied to each test- site on a 2.5 cm. square gauze pad.

Duration of treatment / exposure:

24 h

Observation period:

24 h and 72 h

Number of animals:

Six rabbits ( 3 male and 3 female)

Details on study design:

TEST SITE
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 sits remained intact.

These were covered with aluminum foil secured with "Sleek"* adhesive tape. The test sites were then enclosed by a 6" wide "Cobon” 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.

SCORING SYSTEM:
Primary irritation score Rating
0 Non irritating
0.1 - 0.5 Minimally irritating
0.6 - 1.5 Slightly irritating
1.6 - 3.0 Mildly irritating
3.1 - 5.0 Moderately irritating
5.1 - 6.5 Severely irritating
6.6 - 8.0 Extremely irritating

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animal (intact skin)

Time point:

24 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animal (intact skin)

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animal (Abraded skin)

Time point:

24 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animal (Abraded skin)

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animal (intact skin)

Time point:

24 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animal (intact skin)

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animal (Abraded skin)

Time point:

24 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animal (Abraded skin)

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Time point:

48 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

None

Other effects:

None

Erythema Formation:

No./Sex	Intact		Abraded		Total
	24 hrs	72 hrs	24 hrs	72 hrs
11	0	0	0	0
13	0	0	0	0
15	0	0	0	0
12	0	0	1	0
14	1	0	1	0
16	0	0	0	0
Mean	0.17	0	0.33	0	0.5

Oedema Formation

No./Sex	Intact		Abraded		Total
	24 hrs	72 hrs	24 hrs	72 hrs
11	2	0	3	0
13	0	0	1	0
15	2	0	2	0
12	1	0	1	0
14	3	0	2	0
16	2	0	1	0
Mean	1.67	0	1.67	0	3.33

Total Erythema + Oedema Score = 3.83

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20043/B is a slight to moderate primary skin irritant in the albino rabbit.

Executive summary:

A skin irritation potential was determined of FAT 20043/B according to the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous. Substances Labelling Act Sect. 191.11 (February 1965).

Slight erythema and very slight to moderate edema was seen on 2/6 and 6/6 rabbits respectively, 24 hours after application of the compound. All sites were normal by 72 hours. There was no marked difference in the reactions between abraded and intact sites. The primary irritation score was 1.0. FAT 20043/B is a slight primary skin irritant in the albino rabbit. Based on the finding in the skin irritation studies, the test substance does not need to be classified according to Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (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:

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: 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. 191.12 (February 1965), with slight modification.

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 - 13 weeks
- Weight at study initiation: average body weights of 2.73 kgs. (males) and 2.38 kgs. (females)
- Housing:The rabbits were caged singly in an experimental room.
- Diet: A commercial irradiated diet (Styles-Oxoid) was fed ad libitum.
- Water:Sterile filtered water was available at all times.
- Acclimation period: Six rabbits were acclimatised in the test area for one week prior to the start of the trial

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light): Animals were exposed to artificial light for 10 hours daily

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg.

Duration of treatment / exposure:

30 seconds

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

Six rabbits (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):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.

SCORING SYSTEM: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.

Score Assessment
0 : Non irritant
0 - 10: Minimally irritant
11 - 25: Slightly irritant
26 - 56: Moderately irritant
57 - 84: Markedly irritant
>84: Extremely irritant

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

48 h

Score:

0.83

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

0.16

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

A slight to moderate conjunctival reaction was seen in all treated eyes one hour after application of the compound. This had subsided slightly by 24 hours and thereafter continued to do so until all eyes were normal by 48 hours (1/3 washed) 72 hours (2/3 unwashed 2/3 washed) and 6 days (1/3 unwashed). Staining of the conjunctivae and cornea by the compound was seen in the unwashed eyes for up to 40 hours.

Other effects:

None

Rabbit eye irritation scores-reference procedure:

		1 hour							6 hours							1 Day							2 Days							3 Days							6 Days
	Rabbit No	11	13	15	12	14	16		11	13	15	12	14	16		11	13	15	12	14	16		11	13	15	12	14	16		11	13	15	12	14	16		11	13	15	12	14	16
	Conjuctivae
A	Redness	2	2	2	2	1	1		-	-	-	-	-	-		1	2	1	2	1	1		1	1	-	1	1	1		-	1	-	-	-	-		-	-	-	-	-	-
B	Chemosis	2	2	1	2	1	2		-	-	-	-	-	-		1	1	-	1	-	-		1	1	-	1	-	-		-	-	-	-	-	-		-	-	-	-	-	-
C	Discharge	2	1	-	3	-	-		-	-	-	-	-	-		-	-	-	-	-	-		-	-	-	-	-	-		-	-	-	-	-	-		-	-	-	-	-	-
c=(A+B+C) X2	(max. 20)	12	10	6	14	4	6		-	-	-	-	-	-		4	6	2	6	2	2		4	4	-	4	2	2		-	2	-	-	-	-		-	-	-	-	-	-
Total	(Max.110)	12	10	6	14	4	6		-	-	-	-	-	-		4	6	2	6	2	2		4	4	-	4	2	2		-	2	-	-	-	-		-	-	-	-	-	-

Eyes washed in Nos. 14, 15 & 16 hours

No effects were observed for cornea and iris.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20043/B is a minimal eye irritant in the albino rabbit.

Executive summary:

A study was performed to determine the eye irriattion potential of FAT 20043/B in rabbits according to with the procedure set out in the "Hazardous Substances Regulations" under the U.S.A. "Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification. 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. There was no effects observed for cornea and iris at 24 and 48 h observation period, however redness and discharge were seen but get reversed after 72 hrs. In conclusion, FAT 20043/B is a minimal eye irritant in the albino rabbit and based on the finding in the eye irritation studies, the test substance does not need to be classified according to Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

A skin irritation potential was determined of FAT 20043/B according to the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous. Substances Labelling Act Sect. 191.11 (February 1965). Slight erythema and very slight to moderate edema was seen 24 hours after application of the compound on 2/6 and 6/6 rabbits, respectively. All sites were normal by 72 hours. There was no marked difference in the reactions between abraded and intact sites. The primary irritation score was 1.0. It can be noted that abrasion on skin causes epidermal injury and further expected to cause the skin irritation and adverse effects to epidermis. This reaction could be referred to the damage caused due to abrasion rather than due to the test substance application. In general, abrasion is an elevated testing condition and results normally do not have to be taken into account for hazard assessment. Hence, FAT 20043/B can be considered as non-irritating to rabbit’s skin. In another supporting study, the test was to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound on the skin of the rabbits. The procedure adopted was the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0. Therefore FAT 20043/A is to be considered as non-irritant to the skin of rabbits. Considering the results from key study and supporting study it can be concluded that FAT 20043 is non-irritating to rabbit’s skin.

Eye Irritation:

A study was performed to determine the eye irritation potential of FAT 20043/B in rabbits according to with the procedure set out in the "Hazardous Substances Regulations" under the U.S.A. "Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification. In conclusion, FAT 20043/B is a minimal eye irritant in the albino rabbit. A supporting study was performed to determine the eye irritation potential of FAT 20043/A in rabbits according to the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO). The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 0 for the cornea, 0 for the iris and o for the conjunctivae. Therefore, FAT 20043/A is to be considered non-irritant to the eye of rabbits.

Justification for selection of skin irritation / corrosion endpoint:
Non-GLP guideline study

Justification for selection of eye irritation endpoint:
Non-GLP guideline study

Justification for classification or non-classification

Based on the finding in the skin and eye irritation studies, the test substance does not need to be classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.