Sodium bis[N-(2-chlorophenyl)-2-[[2-hydroxy-5-(N-methylsulphamoyl)phenyl]azo]-3-oxobutyramidato(2-)]cobaltate(1-)

Endpoint summary

Description of key information

Test substance was found to be non-irritant when applied to the intact or abraded rabbit skin as well as to rabbit eye mucosa.

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:

18 July 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:1.9 to 2.2 kg
- Housing:They were housed singly in metal cages (overall dimensions 47x32x34 cm).
- Diet: standard diet of Nafag ad libitum
- Water: ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18±1
- Humidity (%):55±-5
- Photoperiod (hrs dark / hrs light):14 hours light/day

Type of coverage:

occlusive

Preparation of test site:

shaved

Remarks:

electric clipper

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

6 rabbits (3 males and 3 females)

Details on study design:

The shaved skin area on the left side was slightly scarified just before treatment. A gauze patch of 2.5 x 2.5 cm laden with test substance was applied immediately to the prepared skin. The patch was covered with an impermeable foil of 5x5 cm, which was fixed to the body of the animals with adhesive tape. FAT 20 035/A was applied to each side in quantities of 0.5 g. Before application the test material was wetted with tap water. The gauze patches were removed 24 hours after application.

Assessment of irritation
0 = none
>0-1 = minimal
>1 - 2 = slight
>2 - 4 = moderate
>4 - 6 = marked
>6 - 8 = extreme

Irritation parameter:

erythema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Non-irritant and non corrosive.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20035/A was found to be non-irritant when applied to intact or abraded rabbit skin.

Executive summary:

A in vivo test was carried out for finding out the primary irritation index as a measure of the acute irritation on the skin of rabbits with test compound FAT 20035. The method followed was patch test technique as 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).

6 rabbits (3 male and 3 female) were observed for 7 days after test substance application. The shaved skin area on the left side was slightly scarified just before treatment. A gauze patch of 2.5 x 2.5 cm laden with test substance was applied immediately to the prepared skin. The patch was covered with an impermeable foil of 5x5 cm, which was fixed to the body of the animals with adhesive tape. FAT 20 035/A was applied to each side in quantities of 0.5 g . Before application the test material was wetted with tap water. The gauze patches were removed 24 hours after application.

Results showed no adverse reactions at all at any experimental time period, erythema and edema score at 24, 48 and 72 h was '0'. Under the conditions of this experiment FAT 20035/A was found to be non-irritant when applied to the intact or abraded rabbit 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:

experimental study

Adequacy of study:

key study

Study period:

31 Jul 1943- 06 August 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation:1.8 to 2.2 kg
- Housing: kept separately in metal cages (overall dimensions 47x32x34cm)
- Diet: standard diet of Nafag ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14 hours light/day

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

1 minute

Observation period (in vivo):

1, 2,3 and 7 days

Number of animals or in vitro replicates:

6 rabbits (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The eyes of 3 animals were rinsed 1 minute after application with physiologic saline.

SCORING SYSTEM:
0-10 = minimal
11 - 25 = slight
26 - 55 = moderate
56 - 85 = marked
86 - 110 = extreme

TOOL USED TO ASSESS SCORE: slit lamp

Irritation parameter:

cornea opacity score

Remarks:

unrinsed and rinsed eyes

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed and rinsed eyes

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed and rinsed eyes

Basis:

mean

Remarks:

6 animal

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed and rinsed eyes

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Remarks:

unrinsed and rinsed eyes

Basis:

mean

Remarks:

6 animal

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed and rinsed eyes

Basis:

mean

Remarks:

6 animal

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Other effects:

None

Preparation FAT 20 035/A was found to be practically non irritant when applied to the rabbit eye mucosa. Minimal transient conjunctival reaction was noted 1 and 6 hours following instillation. After 24 hours all findings were negative in 2/3 unrinsed and 1/3 rinsed eyes.

Calculation of the primary eye irritation index

 

time after exposure h	mean reaction score of 3 rabbits
	unrinsed eyes (A)			rinsed eyes (B)
	cornea	iris	conjunctiva	cornea	iris	conjunctiva
6	0	0	4.0	0	0	4.7
24	0	0	2.0	0	0	2.0
72	0	0	0	0	0	0
subtotal	0	0	6.0	0	0	6.7
total	6.0			6.7

 

primary irritation index in unrinsed eyes A = 6.0 :3 = 2.0

primary irritation index in rinsed eyes P. = 6.7 -"3 = 2.2

 

effect of rinsing R = A / B = 2.0 / 2.2 = 0.9

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20035/A was found to be practically non irritant when applied to the rabbit eye mucosa.

Executive summary:

A study was performed to determine the eye irritation potential of FAT 20035/A on rabbits. Test method was followed as 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 substance was tested on 6 rabbits of the Russian breed. Amounts of 0.l g of the test substance were introduced into the conjunctival sac of the left eye with a spatula . After application, the eyelids were held open for a few seconds. The right eye was left untreated and served as a control. The eyes of 3 animals were rinsed 1 minute after application with physiologic saline. The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3 and 7 days on the basis of "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO. Preparation FAT 20035/A was found to be practically non-irritant when applied to the rabbit eye mucosa. Minimal transient conjunctival reaction was noted 1 and 6 hours following instillation. After 24 hours all findings were negative in 2/3 unrinsed and 1/3 rinsed eyes. It can be concluded that FAT 20035/A is practically non irritant when applied to the rabbit eye mucosa.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vivo skin irritation:

A in vivo test was carried out for finding out the primary irritation index as a measure of the acute irritation on the skin of rabbits with test compound FAT 20035/A. The method followed was patch test technique as 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). 6 rabbits (3 male and 3 female) were observed for 7 days after test substance application. The shaved skin area on the left side was slightly scarified just before treatment. A gauze patch of 2.5 x 2.5 cm laden with test substance was applied immediately to the prepared skin. The patch was covered with an impermeable foil of 5x5 cm, which was fixed to the body of the animals with adhesive tape. FAT 20 035/A was applied to each side in quantities of 0.5 g. Before application the test material was wetted with tap water. The gauze patches were removed 24 hours after application. Results showed no adverse reactions at all at any experimental time period, erythema and edema score at 24, 48 and 72 h was '0'. Under the conditions of this experiment FAT 20035/A was found to be non-irritant when applied to the intact or abraded rabbit skin.

 

In vivo eye irritation:

A study was performed to determine the eye irritation potential of FAT 20035/A on rabbits. Test method was followed as 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 substance was tested on 6 rabbits of the Russian breed. Amounts of 0.l g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye was left untreated and served as a control. The eyes of 3 animals were rinsed 1 minute after application with physiologic saline.

The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3 and 7 days. Preparation FAT 20035/A was found to be practically non-irritant when applied to the rabbit eye mucosa. Minimal transient conjunctival reaction was noted 1 and 6 hours following instillation. After 24 hours all findings were negative in 2/3 unrinsed and 1/3 rinsed eyes. It can be concluded that FAT 20035/A is practically non-irritant when applied to the rabbit eye mucosa.

 

Based on the results on in vivo skin and eye tests, FAT 20035/A can be regarded as practically non-irritant to rabbit skin and eyes.

 

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study, the test substance 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.