4-[[5-(anilino)carbonyl-2-methoxyphenyl]azo]-3-hydroxynaphthalene-2-carboxamide

Endpoint summary

Description of key information

Skin Irritation:

Introduction.

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit.

Results.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation. Pink staining was noted at all treated skin sites during the study.

Conclusion.

No evidence of skin irritation was noted during the study. The test material produced a primary irritation index of 0.0, a mean eythema value of 0 and mean oedema value of 0 and as such was classified as a non-irritant to rabbit skin.

Eye Irritation:

Introduction.

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

Result

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. No ocular effects were noted at the 48-hour observation.

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:

Experimental start date: 24 October 2000. Experimental completion date: 27 October 200

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Sponsor's identification: ST383
Description: red powder
Batch number: S/No. 8793
Date received: 12 September 2000
Storage conditions: room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK. At the start of the study the animals weighed 2.61 to 2.92 kg and were twelve to sixteen weeks old. After an acclimatisation period of at least five days each animal was given a number.unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet) was allowed throughout the study. The diet and drinking water were considered not to contain any - contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.25 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 rabbits

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.25g of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin (0.5g of test material was found to occupy too great a volume for practicality, therefore, 0.25g which occupied the maximum practical volume of 1.0 ml was used). The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS

Erythema and Eschar Formation Value
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

Oedema Formation
No oedema Value
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of
exposure) 4

Any other skin reactions, if present, were also recorded.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

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

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

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

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

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

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

6

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study.

Other effects:

Pink-coloured staining was noted at all treated skin sites during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

No evidence of skin irritaiton was noted during the study. The test material produced a primary irritation index of 0.0, a mean erythema value of 0 and mean oedema value of 0 and as such was classified as a non-irritant to rabbit skin.

Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “ Acute Dermal Irritation/Corrosion” (adopted 17 July 1992) C

- Commission Directive 92/69/EEC Method B4 Acute Toxicity (Skin Irritation)

Results.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation. Pink staining was noted at all treated skin sites during the study.

Conclusion.

No evidence of skin irritaiton was noted during the study. The test material produced a primary irritation index of 0.0, a mean erythema value of 0 and mean oedema value of 0 and as such was classified as a non-irritant to 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:

Experimental start date: 31 October 2000. Experimental completion date: 05 November 2000.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 (incl. QA statement)

Specific details on test material used for the study:

Sponsor's identification: ST383
Description: red powder
Batch number: S/No. 8793
Date received: 12 September 2000
Storage conditions: room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK. At the start of the study the animals weighed 2.71 to 3.09 kg and were twelve to sixteen weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

0.1 mL of test item, which weighed approximately 20 mg.

Duration of treatment / exposure:

Single application.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

Initially, a single rabbit was treated. A volume of 0.1ml of the test material, which was found to weigh approximately 20 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released.
The left eye remained untreated and was used for control purposes.

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize)

Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Pink-coloured staining of the fur around the treated eye was noted in all animals throughout the study.

No cornea! or iridial effects were noted during the study.

Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and in one treated eye at the 24-hour observation.

No ocular effects were noted at the 48-hour observation.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not produce mean scores following grading at 24, 48 and 72 hours for corneal opacity ≥ 1, iritis ≥ 1, conjunctival redness ≥ 2 or conjunctival oedema (chemosis) ≥ 2, as such it does not meet the requirements to be classified as a irritant to the rabbit eye according to GHS.

Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 405 “ Acute Eye Irritation/Corrosion" (adopted 24 February 1987)

- Commission Directive 92/69/EEC Method B5 Acute Toxicity (Eye Irritation)

Result

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. No ocular effects were noted at the 48-hour observation.

Conclusion

The test item did not produce mean scores following grading at 24, 48 and 72 hours for corneal opacity ≥ 1, iritis ≥ 1, conjunctival redness ≥ 2 or conjunctival oedema (chemosis) ≥ 2, as such it does not meet the requirements to be classified as a irritant to the rabbit eye according to GHS.

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

Skin corrosion / irritation

Skin corrosion is defined as the production of irreversible damage to the skin following application of the test substance. Skin irritation is the production of reversible damage to the skin following application of the test substance. 

An in-vivo skin irritation study in rabbits produced no evidence of skin irritation in any animals . The test material produced a mean erythema value of 0.0 and mean oedema value of 0.0 for each of the 3 animals tested.

The CLP regulation states that a mean value of ≥2.3 - ≤4.0 for erythema or odema is required in at least 2 of 3 animals from gradings at 24, 48 and 72 hours for classification as a skin irritant.

Based on the lack of skin irritation observed, the substance is therefore not classified as a skin irritant.

Eye irritation

Serious eye damage is defined as the production of tissue damage in the eye, or serious physical decay or vision following application of the test substance to the anterior surface of the eye which is not fully reversible. Eye irritation means the production of changes in the eye following application of the test substance which is fully reversible. 

In an in-vivo eye irritation study, a single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. No ocular effects were noted at the 48-hour observation.

The test item did not produce mean scores following grading at 24, 48 and 72 hours for corneal opacity ≥ 1, iritis ≥ 1, conjunctival redness ≥ 2 or conjunctival oedema (chemosis) ≥ 2, as such it does not meet the requirements to be classified as a irritant to the rabbit eye according to CLP.