Reaction mass of Cobaltate(1-), bis[6-(amino-κN)-5-[2-[2-(hydroxy-κO)-4-nitrophenyl]diazenyl-κN1]-N-methyl-2-naphthalenesulfonamidato(2-)]-, sodium (1:1) and disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)

Endpoint summary

Description of key information

FAT 20036 is a non-irritant to skin and eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Environmental Pr otection Agency (EPA), Paragraph 163.81-5 "Primary dermal irritaion study", Federal Register, Vol 43 No. 163, August 22, 1978

Deviations:

yes

Remarks:

Animals have been scarified prior to the treatment. This procedure represents an elevated testing conditions, because the intact skin barrier is destroyed.Therefore care must be taken to use results of these animals for the overall hazard assessment.

GLP compliance:

no

Specific details on test material used for the study:

Code No: FAT 20036/D
Batch No: EN 91018.22
Stability: May 1987
Description: powder
Test Article Received: June 6, 1982

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Weight at study initiation: 2-3 Kg
- Housing: Animals were housed individually in metal cages.
- Diet: Rabbit food, NAFAGf No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water: ad libitum
- Individual identification: ear numbers

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Photoperiod: 12 hours light cycle day
- Air changes: Approximately 15 air changes/h.

Type of coverage:

occlusive

Preparation of test site:

other: shaved and scarified on one side

Vehicle:

unchanged (no vehicle)

Controls:

no

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:

3 male and 3 female rabbits

Details on study design:

24 hours before treatement the flanks of the rabbits were shaved with an electric clipper (approximately 6 sq.cm each) and immediately before treatment, the shaven skin on one side was slightly scarified with the help of a "Schroepfschnaepper", Aesculap, Switzerland.
Gauze patches soaked (or loaded) with 0.5 g of the test material were applied to the prepared abraded and intact skin.
The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after 24 hours.

The skin reaction was assessed upon removal and during a subsequent observation period of 7 days on the basis of the following evaluation scheme.


SCORING SYSTEM:

Erythema and eschar formation
- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4
Total possible erythema score 4

Edema formation
- No edema 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well defined by definite raising): 2
- Moderate edema (raised approximately 1 mm): 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure): 4
Total possible edema score 4

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

1.5

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Time point:

48 h

Score:

1.5

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Time point:

72 h

Score:

1.5

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

48 h

Score:

1.17

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

PRIMARY IRRITATION INDEX = 8.5 / 4 = 2.13

CALCULATION OF THE PRIMARY SKIN IRRITATION INDEX (TABLE 1)

The scores read after 24 and 72 hours for erythema and edema for the intact as well for the abraded skin were summed up and divided by 4 (FHSLA paragraph 191.11)

MEAN REACTION SCORE
	Erythema		Edema
Time after exposure hours	Intact skin	Abraded skin	Intact skin	Abraded skin
24	1.5	1.0	1.3	1.0
72	1.5	1.0	1.0	0.2
Total	3.0	2.0	2.3	1.2	8.5

PRIMARY IRRITATION INDEX =8.5 / 4 = 2.13

ASSESSMENT OF IRRITATION

- no irritation: 0

- minimal : 0.1-1.0

- slight : 1.1 -2.0

- moderate: 2.1-4.0

- marked: 4.1-6.0

- extreme: 6.1-8.0

Interpretation of results:

moderately irritating

Conclusions:

FAT 20036/D was concluded to be not a skin irritant.

Executive summary:

FAT 20036/D was tested for skin irritation potential in a test performed on 3 males and 3 female New Zealand White rabbits. The procedure used is based, but not in every part identical with the Proposed Guidelines of the United States Environmental Pr otection Agency (EPA), Paragraph 163.81-5 "Primary dermal irritaion study", Federal Register, Vol 43 No. 163, August 22, 1978. 24 hours prior to the treatment, the flanks of the rabbits were shaved with an electric clipper (approximately 6 sq.cm each). Immediately before treatment, the shaven skin on one side was slightly scarified with the help of a "Schroepfschnaepper". 0.5 g of the test material was applied to the prepared abraded and intact skin respectively. The skin reaction was assessed upon removal of test material patch and subsequently observed for a period of 7 days.

 

The exposure was found to have some irritation reactions on intact as well as abraded skin, however the scores did not meet the classification criteria as set by Regulation (EC) No. 1272/2008. The calculated primary irritation index was 2.13. Hence, under the conditions of the present experiment FAT 20'036/D wasconcluded to be not a skin irritant.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study". Federal Register, Vol. 43 No. 163 August 22, 1978

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Code No: FAT 20036/D
Batch No: EN 91018.22
Stability: May 1987
Description: Powder
Test Article Received: June 6, 1982

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Hadoerin AG, CH-4414 Fuellinsdorf.
- Weight at study initiation: between 2 to 3 kg.
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): Rabbit foodr NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland).
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 4 days.
- Individual identification: ear numbers.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Photoperiod: 12 hours light cycle day and approximately 15 air changes/h.

Vehicle:

unchanged (no vehicle)

Controls:

other: Right eye of each rabbit remained untreated and served as a control.

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

One single application

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 male and 3 female rabbits

Details on study design:

The test material (0.1 g) was inserted in the conjunctival sac of the left eye of the rabbits and the lids were gently closed for 15 seconds. In 3 of the 6 rabbits, approximately 30 seconds later, In after the treatment the treated eye was flushed with 10 ml of sterile physiological saline.
The eye irritation was assessed with a slit-lamp at 24, 48, 72 hours and 4 and 7 days after treatment.


SCORING SYSTEM:
CORNEA
A. Opacity and degree of density (most dense area scored)
- No opacity: 0
- Scattered or diffuse area, details of iris clearly visible: 1
- Easily discernible translucent aereas, details of iris slightly obscured: 2
- Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
- Opaque, iris invisible: 4

B. Area of cornea involved
- One quarter (or less) but not zero: 1
- Greater than one quarter, but less than half: 2
- Greater than half, but less than three quarters: 3
- Greater than three quarters, up to whole area: 4
A x B x 5
Maximum possible score 80

IRIS
A. Values
- Normal: 0
- Folds above normal, congestion, swelling, circumcornea injection (any or all of theses or combination of any thereof) iris still reaction to light (sluggish reaction is positive): 1
- No reaction to light, hemorrhage, gross destruction (any or all of these): 2
A x 5
Maximum possible score 10

CONJUNCTIVAE
A. Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris)
- Vessels normal: 0
- Vessels definitely injected above normal: 1
- More diffuse, deeper crimson red, individual vessels not easily discernible: 2
- Diffuse beefy red: 3

B. Chemosis
- No swelling 0
- Any swelling above normal (includes nictating membrane): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half closed: 3
- Swelling with lids about half closed to completely closed: 4

C. Discharge
- No discharge: 0
- Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
- Discharge with moistening of the lids and hairs just adjacent to lids: 2
- Discharge with moistening of the l i d s and hairs, and considerable area around the eye: 3
(A + B + C) x 2
Maximum possible score : 20

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Rinsed and non rinsed eyes

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

Rinsed and Unrinsed eye

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Rinsed and unrinsed eye

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

Rinsed and unrinsed eyes

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

FAT 20'036/D was found to cause miniaal irritation when applied to the rabbit eye mucosa.
- PRIMARY IRRITATION INDEX IN UNRINSED EYES: A= 6.7 : 5 = 1.3
- PRIMARY IRRITATION INDEX IN RINSED EYES: B= 4.0 : 5 = 0.8

Other effects:

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20'036/D was concluded to be not an eye irritant.

Executive summary:

An acute eye irritation study was performed on New Zealand white rabbits to determine the irritant potency of FAT 20036/D. The procedure used is based, but not in

every part identical with the Proposed Guidelines of the United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study". Federal Register, Vol. 43 No. 163 August 22, 1978. The test material (0.1 g) was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits, approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

 

No irritation reactions were noticed with cornea and iris. The scores obtained for conjunctival redness and chemosis were below the threshold scores for classification as established by Regulation (EC) No. 1272/2008. The calculated primary irritation index was: 1.3 in unrinsed eyes and 0.8 in rinsed eyes. Hence, it can be concluded that under the conditions of the present experiment FAT 20036/D is not an irritant to eyes.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

Several studies investigating skin irritation poetential of FAT 20036 are available. The exposures sites in these studies included shaved as well as abraded skin on flanks of the rabbits. Some irritation reactions were reported, however the scores did not meet the threshold criteria for classification as set by Regulation (EC) No. 1272/2008. Hence, FAT 20036 is to be considered as not an irritant to the skin.

The key study (1982) was conducted in accordance with the Proposed Guidelines of the United States Environmental Pr otection Agency (EPA), Paragraph 163.81-5 "Primary dermal irritaion study", Federal Register, Vol 43 No. 163, August 22, 1978. The exposure of FAT 20036/D was found to have some irritation reactions on intact as well as abraded skin, however the scores did not meet the classification criteria as set by Regulation (EC) No. 1272/2008. The calculated primary irritation index was 2.13. Hence, under the conditions of the present experiment FAT 20036/D wasconcluded to be not a skin irritant.

Eye:

Several studies investigating eye irritation poetential of FAT 20036 are available. Some irritation reactions with conjunctiva were reported, while no irritation reactions with cornea as well as iris were seen. However, the scores did not meet the threshold criteria for classification as set by Regulation (EC) No. 1272/2008. Hence, FAT 20036 is to be considered as not an irritant to the eyes.

The key acute eye irritation study (1982) was performed on New Zealand white rabbits to determine the irritant potency of FAT 20036/D. The procedure used is based, but not in every part identical with the Proposed Guidelines of the United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study". Federal Register, Vol. 43 No. 163 August 22, 1978. The test material (0.1 g) was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits, approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.No irritation reactions were noticed with cornea and iris. The scores obtained for conjunctival redness and chemosis were below the threshold scores for classification as established by Regulation (EC) No. 1272/2008. The calculated primary irritation index was: 1.3 in unrinsed eyes and 0.8 in rinsed eyes. Hence, it can be concluded that under the conditions of the present experiment FAT 20036/D is not an irritant to eyes.

Justification for classification or non-classification

Based on the above mentioned results, the substance does not need to be classified for the eye and for the skin irritation endpoint.

The degree of skin and eye irritation was insufficient for classification and labelling and thus no classification is proposed for skin irritation.

Therefore, FAT 20036 is classified as non-irritant for skin and eyes.