N-(5-chloro-2,4-dimethoxyphenyl)-4-[[5-[(diethylamino)sulphonyl]-2-methoxyphenyl]azo]-3-hydroxynaphthalene-2-carboxamide

Endpoint summary

Description of key information

Skin Effects

PR005

0.5 g of the test item moistened with tap water was applied to the intact skin of three New Zealand White rabbits under semi-occlusive conditions for twenty four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the test item. A red discoloration was noted on the treated are. No skin reactions, neither erythema nor edema, were observed at any time point (score 0). No signs of systemic toxicity were observed. Therefore, it is concluded that the test item is not irritating to skin.

Eye Effects

PR112

In a OECD guideline and GLP compliant primary eye irritation test in rabbits, Test item (Pigment Red 112) caused grade 1 (1/3 animals) chemosis after one hour and conjunctival reddening grade 1 (3/3 animals) after 1 hours and grade 1 (1/3 animals) after 24 hours. No effects were observed for these and other parameters at the other reading times up to 72 hours. Therefore, Test item (Pigment Red 112) was regarded as not eye irritating.

PO38

The primary eye irritation potential of the test item was investigated according to OECD guideline no 405. The test item (0.1 g) was applied to the intact eye of three New Zealand White rabbits for 1 h. Redding of the conjunctivae was noted in all three animals 1 h after the tratment and persisited up to 48 h in two animals. Slight swelling was noted in one and slight occular discharge was noted in two animals in the 1 h reading.

The individual mean scores calculated across the three scoring times (24, 48, 72 h) were for corneal opacity 0.0 (three animals), for iris 0.0 (three animals), for conjunctivae redding 0.0, 0.7 and 0.7 and for chemosis 0.0 (three animals).

No abnormal findings were observed in the treated eye of any animal 72 h after treatment.

There was no indication of systemic toxicity.

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:

From 06 JUN 2011 to 21 JUN 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study, in compliance with GLP

Qualifier:

according to guideline

Guideline:

other: Biological Evaluation of Medical Devices, Part10: Tests for irritation and Sensitization

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DNA Rabbitry, Elk River, MN, USA
- Age at study initiation: young adults
- Weight at study initiation: 2.6 kg (male), 2.3 kg (female), 2.2 kg (male)
- Housing: individual boxes
- Diet: standard laboratory diet, ad libitum
- Water: tap water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- According to AAALAC International recommendations for rabbits

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: control: wetted patch; positive control: 2.5% and 5% sodium lauryl sulfate

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): a not further quantified amount of tap water was used to moisten the test item

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

3 (2 males, 1 female)

Details on study design:

TEST SITE
- Area of exposure: approximately 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): diluted alcohol
- Time after start of exposure: 24 h

SCORING SYSTEM: in accordance with OECD TG 404, reading at 1, 24, 48 and 72 h after removal of test item

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- No erythema or oedema were observed at any time point.

Other effects:

- no clinical signs recorded
- A red coloration was noted on the treated areas which made it difficult to score for erythema

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not irritating to skin under the test conditions described above. Skin exposure was longer (24 h) than recommended in OECD TG 404 (4 h). No dermal reactions, neither erythema nor edema, were observed.

Executive summary:

The primary skin irritation potential of the test item was investigated according to Biological Evaluation of Medical Devices, Part10: Tests for irritation and Sensitization.

0.5 g of the test item moistened with tap water was applied to the intact skin of three New Zealand White rabbits under semi-occlusive conditions for twenty four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the test item. A red discoloration was noted on the treated are. No skin reactions, neither erythema nor edema, were observed at any time point (score 0). No signs of systemic toxicity were observed.

Therefore, it is concluded that the test item is not irritating to skin.

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

Study period:

21 July - 15 July 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance with OECD and GLP guidelines.

Justification for type of information:

See Rationale and Justification for the Analogue Read-Across Approach for the registration of the Nanoform of Pigment Red 5 (Chapter 13)

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 2 months to 5 months
- Weight at study initiation: 2.9 kg to 3.2 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 2013) ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 2°C (air-condition)
- Humidity (%): 55±10%
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

other: polyethyleneglycol 400

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

One administration 24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place
- Time after start of exposure: see above

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since on effects occured

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

other: grade 1 chemosis was observed in all animals at 1 hour and was fully reversible within 24 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

The score refers to redness of conjunctiva, which was evident in all animals 1 h after treatment (score 1 in all 3 animals). The value of 0.11 is the mean (of the three assessments at 24, 48 and 72 h) for all animals combined as well as for each individual animal. At 48 and 72 h, this score was 0 in all animals. Other parameters examined (opacity of cornea, iris, chemosis of conjunctiva) showed scores of 0 at the relevant time points.

Other effects:

Red staining of eye discharge was observed at 1 hour after application.

Conclusions:

67/548/EEC: Eye irritation: no classification warranted
1272/2008/EC: Eye irritation: no classification warranted

In a OECD guideline and GLP compliant primary eye irritation test in rabbits, Test item (Pigment Red 112) caused grade 1 (1/3 animals) chemosis after one hour and conjunctival reddening grade 1 (3/3 animals) after 1 hours and grade 1 (1/3 animals) after 24 hours. No effects were observed for these and other parameters at the other reading times up to 72 hours. Therefore, Test item (Pigment Red 112) was regarded as not eye irritating.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 July - 15 July 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance with OECD and GLP guidelines.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 2 months to 5 months
- Weight at study initiation: 2.9 kg to 3.2 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 2013) ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 2°C (air-condition)
- Humidity (%): 55±10%
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

other: polyethyleneglycol 400

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

One administration 24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place
- Time after start of exposure: see above

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since on effects occured

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

other: grade 1 chemosis was observed in all animals at 1 hour and was fully reversible within 24 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

The score refers to redness of conjunctiva, which was evident in all animals 1 h after treatment (score 1 in all 3 animals). The value of 0.11 is the mean (of the three assessments at 24, 48 and 72 h) for all animals combined as well as for each individual animal. At 48 and 72 h, this score was 0 in all animals. Other parameters examined (opacity of cornea, iris, chemosis of conjunctiva) showed scores of 0 at the relevant time points.

Other effects:

Red staining of eye discharge was observed at 1 hour after application.

Conclusions:

67/548/EEC: Eye irritation: no classification warranted
1272/2008/EC: Eye irritation: no classification warranted

In a OECD guideline and GLP compliant primary eye irritation test in rabbits, Test item (Pigment Red 112) caused grade 1 (1/3 animals) chemosis after one hour and conjunctival reddening grade 1 (3/3 animals) after 1 hours and grade 1 (1/3 animals) after 24 hours. No effects were observed for these and other parameters at the other reading times up to 72 hours. Therefore, Test item (Pigment Red 112) was regarded as not eye irritating.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

From 30 APR 2007 to 10 MAY 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 405; EU method B5), in compliance with GLP

Justification for type of information:

See Rationale and Justification for the Analogue Read-Across Approach for the registration of the Nanoform of Pigment Red 5 (Chapter 13)

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gerome (Quartier Labaste, Linxe, France)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: between 2.63 and 3.04 kg, all within the normal range of variability
- Housing: individual boxes
- Diet: standard laboratory diet. ad libitum
- Water: tap water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 (air condition)
- Humidity (%): 42-68
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

1 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3 (female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with isotonic solution
- Time after start of exposure: 1 h

SCORING SYSTEM: according to OECD TG 405, reading at 1, 24, 48 and 72 h after removal of test item

TOOL USED TO ASSESS SCORE: occular examination

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24,48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effect

Irritant / corrosive response data:

Slight reddening of the conjunctivae was noted in the three animals 1 h after treatment and persisted up to 48 h in two animals.
1 h reading: slight swelling (chemosis) in 1 animal, slight occular discharges in all treated animals
24 h and 48 h reading: slight conjunctivae redness in 2 animals.
72 h reading: no abnormal findings observed in any animal.

No coloration of the treated eyes was noted at any of the reading times.

Other effects:

- changes in body weight during the course of the study were not remarkable.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not irritating to skin when tested under the conditions of the OECD guideline 405.

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD guideline no 405. The test item (0.1 g) was applied to the intact eye of three New Zealand White rabbits for 1 h. Redding of the conjunctivae was noted in all three animals 1 h after the tratment and persisited up to 48 h in two animals. Slight swelling was noted in one and slight occular discharge was noted in two animals in the 1 h reading.

The individual mean scores calculated across the three scoring times (24, 48, 72 h) were for corneal opacity 0.0 (three animals), for iris 0.0 (three animals), for conjunctivae redding 0.0, 0.7 and 0.7 and for chemosis 0.0 (three animals).

No abnormal findings were observed in the treated eye of any animal 72 h after treatment.

There was no indication of systemic toxicity.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 30 APR 2007 to 10 MAY 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 405; EU method B5), in compliance with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gerome (Quartier Labaste, Linxe, France)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: between 2.63 and 3.04 kg, all within the normal range of variability
- Housing: individual boxes
- Diet: standard laboratory diet. ad libitum
- Water: tap water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 (air condition)
- Humidity (%): 42-68
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

1 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3 (female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with isotonic solution
- Time after start of exposure: 1 h

SCORING SYSTEM: according to OECD TG 405, reading at 1, 24, 48 and 72 h after removal of test item

TOOL USED TO ASSESS SCORE: occular examination

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24,48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not relevant since no effects

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effect

Irritant / corrosive response data:

Slight reddening of the conjunctivae was noted in the three animals 1 h after treatment and persisted up to 48 h in two animals.
1 h reading: slight swelling (chemosis) in 1 animal, slight occular discharges in all treated animals
24 h and 48 h reading: slight conjunctivae redness in 2 animals.
72 h reading: no abnormal findings observed in any animal.

No coloration of the treated eyes was noted at any of the reading times.

Other effects:

- changes in body weight during the course of the study were not remarkable.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not irritating to skin when tested under the conditions of the OECD guideline 405.

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD guideline no 405. The test item (0.1 g) was applied to the intact eye of three New Zealand White rabbits for 1 h. Redding of the conjunctivae was noted in all three animals 1 h after the tratment and persisited up to 48 h in two animals. Slight swelling was noted in one and slight occular discharge was noted in two animals in the 1 h reading.

The individual mean scores calculated across the three scoring times (24, 48, 72 h) were for corneal opacity 0.0 (three animals), for iris 0.0 (three animals), for conjunctivae redding 0.0, 0.7 and 0.7 and for chemosis 0.0 (three animals).

No abnormal findings were observed in the treated eye of any animal 72 h after treatment.

There was no indication of systemic toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification, as no adverse effects were observed.