Benzyl 4-[(1-butyl-5-cyano-1,6-dihydro-2-hydroxy-4-methyl-6-oxopyridin-3-yl)azo]benzoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 August to 15 August, 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disperse Yellow 231

IUPAC Name:

Disperse Yellow 231

Test material form:

solid: particulate/powder

Test animals

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: 12 to 16 weeks old
- Weight at study initiation: 2.28 to 3.28 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum; Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, UK
- Water: ad libitum; mains drinking water
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 21 °C
- Humidity: 65 - 68 %
- Air changes: 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12 controlled by a time switch

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

fur of the dorsal/flank areas was closely clipped using veterinary clippers approximately 24 hours before the test

Vehicle:

water

Remarks:

slightly moistened with 0.5 ml distilled water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

- Amount applied: 0.5 g in 0.5 ml distilled water
- Negative control: untreated surrounding skin

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after removal of substance

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsal area
- Type of coverage if used: 2.5 × 2.5 cm gauze patch, secured with surgical adhesive tape (Blenderm; ca. 25 × 40 mm); then the trunk of the animal was wrapped in elasticated corset (Turbigrip)

REMOVAL OF TEST SUBSTANCE
- Removal: gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- 1, 24, 48 and 72 hours after removal of patch/test item

SCORING SYSTEM:
- Method of calculation: Draize, J. H. (1959) "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", as follows:

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

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

edema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

Very slight erythema was noted in all three animals at 1 hour after removal of the substance. Only one animal still showed slight erythema at 24 hours after exposure, which was reversible within 48 hours after exposure.
No oedema was observed.

Other effects:

Faint yellow coloured staining of the treatment sites was noted in all three animals which lasted until the end of the study period.

Any other information on results incl. tables

Table 1: Individual daily and individual mean scores for dermal irritation/corrosion.

Skin reaction	Reading (hours)	Individual scores
		#1	#2	#3
Erythema/eschar formation	1	1s	1s	1s
	24	0s	1s	0s
	48	0s	0s	0s
	72	0s	0s	0s
	total (24, 48, 72 h)	0	1	0
	mean (24, 48, 72 h)	0.0	0.3	0.0
Oedema formation	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0
	total (24, 48, 72 h)	0	0	0
	mean (24, 48, 72 h)	0.0	0.0	0.0

s = faint yellow-coloured staining over the test site not affecting evaluation of erythema

Applicant's summary and conclusion

Interpretation of results:

other: not classified according to the CLP Regulation (EC 1272/2008)

Conclusions:

The test item was very slightly irritating to rabbit skin until 24 hours; skin was stained slightly yellow locally.

Executive summary:

The potential skin irritation/corrosion of the test item was evaluated in an experimental study according to a method based on the OECD guideline 404 (1981). The dorsal fur of three New Zealand White rabbits was clipped free of hair and 0.5 mg of test item moistened with 0.5 ml of distilled water was applied under a gauze. After four hours, the substance was removed with cotton and water, and observations of erythema and oedema were recorded at 1, 24, 48 and 72 hours after exposure.

Very slight erythema was noted in all three animals 1 hour after exposure. Only one animal still showed slight erythema 24 hours after exposure, which was reversible within 48 hours. No oedema was observed. Faint yellow coloured staining of the treatment sites was noted in all three animals which lasted until the end of the study period. The mean (24, 48 and 72 h) irritation scores for (i) erythema and (ii) oedema were subsequently calculated to be (i) 0 in two animals and 0.33 in one animal, and (ii) 0 in all animals.