Trisodium 5-[[5-[[4-chloro-6-[(3-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl]azo]-1-ethyl-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-3-methanesulphonate

Endpoint summary

Description of key information

The source substance is non-irritant to rabbit skin and rabbit 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:

supporting study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

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 (AFD0).

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.0 to 2.8 kg
- Diet (e.g. ad libitum): standard diet of Nafag ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 8 days

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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.5 g of the test substance was applied to the skin

Duration of treatment / exposure:

4 hours

Observation period:

after 1, 24, 48, 72 hours

Number of animals:

3 animals

Details on study design:

None

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000 is to be considered as a non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40000, on the skin of the rabbits. Not less than 24 hours before treatment on the back of the experimental animal an area was shaven of at least 6 sq. cm, by means of an electric clipper. A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape. The substance was water moistened before application. Exposure duration was 4 hours. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated after 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. The animals showed a normal body weight development. It can be concluded, that FAT 40000 is non irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days. According to the EC classification of the results obtained, FAT 40000 can be classified as non-irritant in albino rabbits.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

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
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2300 - 2600 g
- Housing: Animals were housed individually in metal cages
- Diet (e.g. ad libitum): Rabbit food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.5 g of the test substance was applied to the skin

Duration of treatment / exposure:

4 hours

Observation period:

after 1, 24, 48, 72 hours

Number of animals:

3 animals

Details on study design:

None

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000/D is to be considered as a non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40000/D, on the skin of the rabbits. Not less than 24 hours before treatment on the back of the experimental animal an area was shaven of at least 6 sq. cm, by means of an electric clipper. A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape (ISOPLAST AG, CH-5200 Brugg). The substance was water moistened before application. Exposure duration was 4 hours. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated after 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. The animals showed a normal body weight development. It can be concluded, that FAT 40000/E is non irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days. According to the EC classification of the results obtained, FAT 40000/D can be classified as non-irritant in albino rabbits.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

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
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2020-2130 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): Rabbit food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 30-70 %;
- Air changes (per hr): 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.5 g of the test substance was applied to the skin

Duration of treatment / exposure:

4 hours

Observation period:

after 1, 24, 48, 72 hours

Number of animals:

3 animals

Details on study design:

None

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000/E is to be considered as a non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40000/E, on the skin of the rabbits. Not less than 24 hours before treatment on the back of the experimental animal an area was shaven of at least 6 sq. cm, by means of an electric clipper. A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape (ISOPLAST AG, CH-5200 Brugg). The substance was water moistened before application. Exposure duration was 4 hours. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated after 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. The animals showed a normal body weight development. It can be concluded, that FAT 40'000/E is non irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days. According to the EC classification of the results obtained, FAT 20202/D can be classified as non-irritant in albino rabbits.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

yes

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

other: Chbbibm: NZW (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH Postfach 1755 0·7950 Biberach a.d. Riss
- Age at study initiation: 15 weeks
- Weight at study initiation: male : 2.8 kg females: 3.2 kg
- Housing: Individually in stainless steel cages (size: 86 x 54 x 33 em) equipped with feed hoppers and drinking water bottles.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 69/92 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum.
- Water (e.g. ad libitum): Community tap water from FOllinsdorf, ad libitum
- Acclimation period: Five days under test conditions after veterinary examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark, music during the light period.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.5 g of substance was applied.

Duration of treatment / exposure:

4 hours

Observation period:

None

Number of animals:

1 male
2 females

Details on study design:

None

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000 is to be considered as a non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40000, on the skin of the rabbits. 0.5 g of the test article was applied to approx. 6 cm² of the intact skin of the clipped area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm-tap water. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. The application site was yellow stained up to 24 hours after the application; therefore the evaluation of a possible erythema formation was impeded. Because no erythema reactions were observed at 24 to 72 hrs and no edema reactions at 24 to 72 hrs after removing the bandages, the test was ended after the 72 hours evaluation. According to the EC classification of the results obtained, FAT 40000/G can be classified as non-irritant in albino rabbits.

Reference 5

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is the meta-isomer of the dye Reactive Yellow 095, where the sulphonate group is bound at the meta-position of the amino benzene moiety. The source chemical is the reaction mass of both the meta-isomer and the para-isomer of Reactive Yellow 095.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.
2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Yellow 095 meta/para (CAS# --- / EC# 944-218-2)
Target: Reactive Yellow 095 meta (CAS# 84045-63-6 / EC# 281-865-3)
3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.12 Auto flammability

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine the primary-irritation index of the source substance, which serves as a measure of the acute irritation on the skin of the rabbits. 0.5 g of the test article was applied to approx. 6 cm² of the intact skin of the clipped area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm-tap water. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. The application site was yellow stained up to 24 hours after the application; therefore the evaluation of a possible erythema formation was impeded. Because no erythema reactions were observed at 24 to 72 hrs and no edema reactions at 24 to 72 hrs after removing the bandages, the test was ended after the 72 hours evaluation. According to the EC classification of the results obtained, the source substance can be classified as non-irritant in albino rabbits.

Three supporting studies performed with the source substance showed similar results.

The structurally related target substance will show the same behaviour and will therefore be non-irritant to skin as well.

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is the meta-isomer of the dye Reactive Yellow 095, where the sulphonate group is bound at the meta-position of the amino benzene moiety. The source chemical is the reaction mass of both the meta-isomer and the para-isomer of Reactive Yellow 095.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.
2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Yellow 095 meta/para (CAS# --- / EC# 944-218-2)
Target: Reactive Yellow 095 meta (CAS# 84045-63-6 / EC# 281-865-3)
3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.12 Auto flammability

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.89

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48h

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is considered to be non-irritant to eyes.

Executive summary:

In a study performed to determine the eye irritation potential of the source substance, the test substance was instilled in the eyes of 3 rabbits and observations for irritation were recorded at the time points of 1 hour, 24 hours, 48 hours 72 hours. The source substance is considered to be a non-irritant to the eyes.

The structurally related target substance will show the same behaviour and will therefore not be classied as an eye irritant either.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

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).

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

other: Russian : breed

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: from suppliers in Switzerland
- Weight at study initiation: 2.4 to 3.0 kg
- Housing: metal cages (overall dimensions 47x32x34 cm)
- Diet (e.g. ad libitum): standard diet of Nafag ad libitum
- Water (e.g. ad libitum): water ad libitum

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

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 g of the test substance were introduced

Duration of treatment / exposure:

3 animals were rinsed with physiologic saline after 1 minute
3 animals were did not receive any rinsing throughout the study

Observation period (in vivo):

1 and 6 hours; 1, 2, 3, 6 and 8 days

Duration of post- treatment incubation (in vitro):

None

Number of animals or in vitro replicates:

None

Details on study design:

None

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000 is considered to be a non-irritant to the eyes.

Executive summary:

In a study performed to determine the eye irritation potential of FAT 40000, test substance was instilled in the eyes of 6 rabbits and observations for irritation were recorded at the time points of 1 hour, 6 hours, 24 hours, 48 hours 72 hours, 6 days and 8 days. Amounts of 0.1 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.According to the EC classification of the r esults obtained after instillation FAT 40000 can be classified as non-irritant to albino rabbit's eye. The eye reactions observed were fully reversible within 72 hours. FAT 40000 is considered to be a non-irritant to the eyes.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2200 - 2400 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): Rabbit food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 ml of the test article

Duration of treatment / exposure:

None

Observation period (in vivo):

1, 24, 48, and 72 hours after substance instillation

Duration of post- treatment incubation (in vitro):

None

Number of animals or in vitro replicates:

None

Details on study design:

None

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

1

Reversibility:

fully reversible within: 72h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000/D is considered to be a non-irritant to the eyes.

Executive summary:

In a study performed to determine the eye irritation potential of FAT 40000/D, test substance was instilled in the eyes of 3 rabbits and observations for irritation were recorded at the time points of 1 hour, 24 hours, 48 hours 72 hours. 0.1 ml of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as the control. According to the EC classification of the results obtained 24 t o 72 hours after instillation FAT 40000/D can be classified as non-irritant to albino rabbit's eye. The eye reactions observed were fully reversible within 72 hours. FAT 40000/D is considered to be a non-irritant to the eyes.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 1900-2120 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): Rabbit food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 30-70 %
- Air changes (per hr): 12 hours light/day
- Photoperiod (hrs dark / hrs light): approximately 15 air changes/h.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 g of the test article

Duration of treatment / exposure:

None

Observation period (in vivo):

1, 24, 48, and 72 hours after substance instillation

Duration of post- treatment incubation (in vitro):

None

Number of animals or in vitro replicates:

3 animals

Details on study design:

None

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24h

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000/E is considered to be a non-irritant to the eyes.

Executive summary:

In a study performed to determine the eye irritation potential of FAT 40000/E, test substance was instilled in the eyes of 3 rabbits and observations for irritation were recorded at the time points of 1 hour, 24 hours, 48 hours 72 hours. 0.1 g of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as the control. According to the EC classification of the r esults obtained 24 t o 72 hours after instillation FAT 40000/E can be classified as non-irritant to albino rabbit's eye. The eye reactions observed were fully reversible withini 7 days. FAT 40000/E is considered to be a non-irritant to the eyes.

Reference 5

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Principles of method if other than guideline:

None

GLP compliance:

yes

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Postfach 1755, D-7950 Biberach an der Riss
- Age at study initiation:15 weeks
- Weight at study initiation: male : 2.9 kg females: 2.4 - 2.8 kg
- Housing: Individually in stainless steel cages (size: 86 x 54 x 33 cm) equipped with feed
hoppers and drinking water bottles.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 69/92 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum. Results of analysis for
contaminants are included in this report.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are included in this report.
- Acclimation period: Five days under laboratory conditions after veterinary examination. Only animals without any visual signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 40-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux)/12 hours dark, music during the light period.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 g of the test article

Duration of treatment / exposure:

None

Observation period (in vivo):

1, 24, 48 and 72 hours and 7 days after administration.

Duration of post- treatment incubation (in vitro):

None

Number of animals or in vitro replicates:

1 male
2 females

Details on study design:

None

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.89

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40000/G is considered to be non-irritant to the eyes.

Executive summary:

In a study performed to determine the eye irritation potential of FAT 40000/G, test substance was instilled in the eyes of 3 rabbits and observations for irritation were recorded at the time points of 1 hour, 24 hours, 48 hours 72 hours. On test day 1, 0.1 g of the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control. FAT 40000/G 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

The following information is available for the source substance:

A study was performed to determine the primary-irritation index, according to OECD TG 404. of the source substance. The application site was yellow stained up to 24 hours after the application; therefore the evaluation of a possible erythema formation was impeded. Because no erythema reactions were observed up to 72 hrs and no edema reactions up to 72 hrs after removing the bandages, the test was ended after the 72 hours evaluation.

Three supporting studies conducted with the source substance showed similar results.

According to CLP criteria, the substance does not need to be classified for skin irritation.

In a study performed to determine the eye irritation potential of the source substance, according to OECD TG 405, test substance was instilled in the eyes of 3 rabbits and observations for irritation were recorded at the time points of 1 hour, 24 hours, 48 hours 72 hours. All effects were fully reversible within 72 hours.

Three supporting studies conducted with the source substance showed similar results.

According to CLP criteria, the substance does not need to be classified for eye irritation.

Justification for classification or non-classification

The source substance is non-irritant to rabbit skin and to rabbit eyes. It is anticipated that the structurally related target substance will show the same behaviour. Therefore it will not be classified for skin irritation and eye irritation either.