5-[(4-chloro-2-nitrophenyl)azo]-1-ethyl-1,2-dihydro-6-hydroxy-4-methyl-2-oxonicotinonitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The experiment started: January 21, 1980; Experiment and study completion date: 04 February 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The procedure used is described in the Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81- 5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978

Deviations:

not specified

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-[(4-chloro-2-nitrophenyl)azo]-1-ethyl-1,2-dihydro-6-hydroxy-4-methyl-2-oxonicotinonitrile

EC Number:

274-660-5

EC Name:

5-[(4-chloro-2-nitrophenyl)azo]-1-ethyl-1,2-dihydro-6-hydroxy-4-methyl-2-oxonicotinonitrile

Cas Number:

70528-90-4

Molecular formula:

C15H12ClN5O4

IUPAC Name:

5-[(4-chloro-2-nitrophenyl)diazenyl]-1-ethyl-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

Test material form:

not specified

Specific details on test material used for the study:

Name: FAT 36019/D
Purity: 50.2 %

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The test was performed on 3 male and 3 female adult New Zealand White rabbits bred and raised on the premises weighing 2 to 3 kgs. They were housed individually in metal cages, numbered by ear tags, were kept at a constant room temperature of 22 ± 2 °C, at a relative humidity of 55 ± 10 % and on a 10 hours light cycle day. The animals received ad libitum standard rabbit food - NAFAG, No. 814, Gossau SG - and water. Prior to treatment they were adapted to our laboratories for a minimum of 4 days.

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved and slightly scarified

Vehicle:

other: Propylene glycol+saline (70:30 parts), concentration 50%

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

3 male and 3 female rabbits

Details on study design:

Before treatment the entire back and the flank of the rabbits were shaved with an electric clipper and immediately before treatment the shaven skin on one side was slightly scarified with the help of a "SchröpfSchnäpper", Aesculap, Switzerland. Gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material were applied to the prepared abraded and intact skin. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after a 24 hour application. The skin reaction was appraised upon removal and during an observation period of 7 days on the basis of the following evaluation scheme.

Score for skin irritation in rabbits
Erythema and eschar formation
- 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
Total possible erythema score 4

Edema formation
- No edema: 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well defined by definite raising): 2
- Moderate edema (raised approximately 1 mm): 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure): 4
Total possible edema score: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Due to intensive staining by the test compound erythema was not assessable. For the purpose of calculating the primary irritation index erythema was assumed to be equal to edema based on the correlation existing (Marzulli and Maibach, Fol. Cosm. Tox. 13, 355, 1975). FAT 36091/D was found to cause a slight irritation when applied to intact and abraded rabbit skin.

Any other information on results incl. tables

Calculation of the primary skin irritation index

The scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4. (FHSLA § 191.11)

	MEAN REACTION SCORE OF 6 RABBITS
	ERYTHEMA		EDEMA
Time after exposure	Intact skin	Abraded skin	Intact skin	Abraded skin
24 hours	0	1.3	0	1.3
72 hours	0	0.8	0	0.8
Total	0	2.1	0	2.1	4.2

primary irritation index = 4.2 / 4 = 1.1

Assessment of irritation

0 = none

>0 - 1 = minimal

>1 - 2 = slight

>2 - 4 = moderate

>4 - 6 = marked

>6 - 8 = extreme

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 36091/D was found to cause a slight irritation when applied to intact and abraded rabbit skin.

Executive summary:

The skin irritation in albino rabbits after single application was performed to determine the irritant potency of the test item on the albino rabbit skin. The procedure used is described in the Proposed Guidelines of the United States Environmental Agency (EPA) 163.81-5 "Primary dermal irritation study", Federal Register Vol. 43, No. 163, August 22, 1978. The test was performed on 3 male and 3 female (New Zealand White rabbits), checked for normal skin conditions. Before treatment the flanks of the rabbits were shaved and immediately before treatment, the shaven skin on one side was slightly scarified. A gauze patch bearing 0.5 g of the test substance was applied to the prepared abraded and intact skin. The patches were covered by an impermeable material. Patches were held in place for 24 hours. Observations were made at 24, 48, 72 hours and 7 days, respectively. Due to intensive staining by the test compound erythema was not assessable. For the purpose of calculating the primary irritation index erythema was assumed to be equal to edema based on the correlation existing (Marzulli and Maibach, Fol. Cosm. Tox. 13, 355, 1975). The 24/48/72h mean erythema score and edema score was found to be 0 and 1 respectively. The effects were fully reversible within 7 days of observation period. Under the conditions of the present experiment FAT 36091/D was found to cause a minimal to slight irritation when applied to intact and abraded rabbit skin. The calculated primary irritation index was 1. FAT 36091/D was found to cause a minimal to slight irritation when applied to intact and abraded rabbit skin. In general, abration represents an elevated test condition that does normally not need to be taken into account for evaluation of the hazard assessment. Therefore, results on abraded skin are not taken into account.