4-[(1-butyl-5-cyano-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl)azo]-N-(2-ethylhexyl)benzenesulphonamide

Endpoint summary

Description of key information

The test substance is considered as not irritating to the skin and eyes of rabbits.

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:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

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)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.77 to 2.99 kg
- Housing: individually housed in suspended metal cages
- Diet: Free access to food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water: Free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: moistened with water

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

72h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsal flank
- Type of wrap if used: elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in distilled water .
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72h

Score:

0

Max. score:

0

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study .

Other effects:

Yellow-coloured staining was noted at all treated skin sites throughout the study. The staining did not affect evaluation of skin responses.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation. The test material produced a primary irritation index of 0.0 and was classified as nonirritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

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:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

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)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.51 to 2.93 kg
- Housing: individually in suspended metal cages
- Diet: Free access to food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water: Free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (about 54 mg)

Duration of treatment / exposure:

single instillation

Observation period (in vivo):

72h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-72h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-72h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-72h

Score:

0.1

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72h

Score:

0.1

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

Moderate conjunctival irritation was noted in all treated eyes at the 1-hour observation. Moderate conjunctival irritation was noted in one treated eye at the 24-hour observation with minimal conjunctiva! irritation at the 48-hour observation. Diffuse corneal opacity was noted in one treated eye at the 24-hour observation. No other corneal effects were noted. lridial inflammation was noted in one treated eye at the 1 and 24-hour observations. No other iridial effects were noted.

Other effects:

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

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Mild irritation responses were reported well below the threshold for classification.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405. A single application of the test material to the non-irrigated eye of three rabbits produced diffuse corneal opacity, iridial inflammation and moderate conjunctiva! irritation. No ocular effects were noted at the 72-hour observation. The test material produced a maximum group mean score of 11 .0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as irritant according to EU labelling regulations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A GLP-compliant study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit (Safepharm, 2000). The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404. A single 4-hour, semi-occluded application of 0.5g of the test material (moistened with water) to the intact skin of three rabbits produced no evidence of skin irritation. The test material produced a primary irritation index of 0.0 and was classified as nonirritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

In a supporting non-GLP study the test substance was applied as paste (0.5 g test substance with 0.5 ml water) under occlusive conditions to the intact or scarified flank of six rabbits (Institut Francais de Recerches et Essais Biologiques, 1979). After 24 hours the patches were removed. One hour later the dermal reactions were evaluated and 48 hours later, a second reading was made to determine the extent of any recovery (the two readings were performed respectively 25 and 72 hours after the application of the substance). On the 7th day another reading was made. All scores measured at any time point for erythma and edema were zero for all animals. Based on the results of this study, the test substance was considered to be not irritating.

Eye irritation

A GLP-compliant study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit (Safepharm, 2000). The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405. A single application of the test material (ca. 0.5 ml) to the non-irrigated eye of three rabbits produced moderate conjunctival irritation in all treated eyes at the 1-hour observation. Moderate conjunctival irritation was noted in one treated eye at the 24 -hour observation with minimal conjunctival irritation at the 48-hour observation. Diffuse corneal opacity was noted in one treated eye at the 24-hour observation. No other corneal effects were noted. lridial inflammation was noted in one treated eye at the 1 and 24-hour observations. No other iridial effects were noted. No ocular effects were noted in all treated eyes at the 72-hour observation. The reported ocular effects were mild and well below the regulatory threshold, therefore the test article is considered to not irritating to the rabbit eye.

In supporting non-GLP study, 100 mg of the test substance was applied undiluted into the conjunctival sac of the right eye of six rabbis (Institut Francais de Recerches et Essais Biologiques, 1979). The eyelids were held closed for several seconds, moved gently up and down and avoiding loss of test substance. The left eyes remained untreated and served as controls. Ocular reactions were recorded after 1 hour, 1 day, 2 days, 3 days, 4 days and 7 days. Minimal signs of irritation involving conjunctiva, cornea and iris below the regulatory threshold were observed at the 1 hour time point. The reactions were getting weaker starting at the 24 hour mark and were reversed to normal after 72 hours. Based on the results of this study, the test article was considered to be not irritating to the rabbit eyes.

Justification for selection of skin irritation / corrosion endpoint:
GLP-compliant guideline study

Justification for selection of eye irritation endpoint:
GLP-compliant guideline study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for irritation is not warranted under Directive 67/548/EEC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for irritation is not warranted under Regulation (EC) No.1272/2008.