N,2-dimethyl-N-phenylbutyramide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-04-05 to 1988-04-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

no

Remarks:

The study pre-dates the introduction of GLP

Test material

Test material information

Constituent 1

Reference substance name:

N,2-dimethyl-N-phenylbutyramide

EC Number:

282-817-4

EC Name:

N,2-dimethyl-N-phenylbutyramide

Cas Number:

84434-18-4

Molecular formula:

C12H17NO

IUPAC Name:

N,2-dimethyl-N-phenylbutanamide

impurity 1

Reference substance name:

Unknown impurities

Molecular formula:

Unknown

IUPAC Name:

Unknown impurities

Test material form:

liquid

Specific details on test material used for the study:

Substance name: Gardamide
Storage: Ambient
Stability: Stable to air and sunlight

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

New Zealand white rabbits, bought from commercial supplier, are used for testing when the hair is in the telegon (non-growh) phase of the hair cycle. Three to four days prior to testing, the dorsal area of thee trunk of healthy adult animals are clipped to identify those which are in telogen and which have no skin blemishes. Of these suitable rabbits, at least three and normally are selected for the test. A final clipping of the test animals is made approximately twenty-four hours before testing.
Throughout testing the rabbits are caged individually and have free access to water and pelleted food.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated skin of each animal serves as its own control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration: 100 %

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Rabbits are used for testing when the hair is in the telogen (non-growth) phase of the hair cycle. Three to four days prior to testing, the dorsal area of the trunk of healthy adult animals is clipped to identify those which are in telogen and which have no skin blemishes. A final clipping of the test animals is made approximately twenty-four hours before testing.
- Test patch: The test material is applied to a semi-occlusive patch. Each patch consists of a 25 x 25 mm gauze pad, backed by a 20 x 30 mm strip of thin polythene film stuck to a 25 x 75 mm strip of zinc oxide sticking plaster.
- Type of wrap if used: After patch application, each rabbit is immobilised in a canvas body sleeve and placed in a quiet place for the exposure duration.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After patch removal, excess test material is wiped from the skin with a damp tissue.
- Time after start of exposure: 4 hours

ASSESSMENT OF IRRITATION
Animals are observed for signs of erythema and oedema and the responses graded at thirty to sixty minutes, and then at twenty-four, forty-eight, and seventy-two hours after patch removal. Dermal irritation is graded and recorded according to the system below. Further observations may be needed, as necessary, to establish lesions such as corrosion (irreversible destruction of skin tissue). Other toxic effects should be fully described.

SCORING SYSTEM:
>Erythema and eschar formation scores
0 = No erythema
1 = Very slight erythema
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 (edges raised by approximately 1mm)
4 = Severe oedema (raised more than 1mm and extending beyond the area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour

Score:

4

Max. score:

4

Reversibility:

not specified

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour

Score:

2

Max. score:

4

Reversibility:

not specified

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: Mean of 24, 48 and 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: Mean of 24, 48 and 72 hour

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

Two animals showed slight erythema of 48 hours duration. One animal showed marked erythema with a small area if necrosis. Histological examination of this area revealed shallow necrosis.

Any other information on results incl. tables

Table 1: Daily Macroscopic Assessment of Irritation Reactions

Animal Number	Erythema					Oedema
	1 Hour	24 Hours	48 Hours	72 Hours	Mean	1 Hour	24 Hours	48 Hours	72 Hours	Mean
9589	0	1	1	0	0.67	0	0	0	0	0
9457	3*	4**	4	4	4	3	2	2	2	2
9401	0	1	1***	0	0.67	0	0	0	0	0

* 0.5 x 0.5 cm patch of beet-red tissue

** 0.5 x 0.5 cm area of dark red/brown tissue

*** Skin starting to crack

 

The skin site of exposure from animal number 9457 was examined histologically. The depth of necrosis/slough was determined to be trace/well developed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test material was determined to be not irritating to the skin.

Executive summary:

The skin irritation potential of the test material was investigated in a study which was conducted in accordance with the standardised guideline EU Method B.4.

During the study 0.5 mL of the undiluted test material was applied to the clipped skin of three healthy New Zealand White rabbits for 4 hours in a semi-occlusive fashion.

Irritation reactions were assessed one hour after removal of the patch and thereafter at 24, 48, and 72 hours.

One animal showed slight erythema for a duration of 48 hours. One animal showed marked erythema and moderate oedema, with a small area of necrosis. Histological examination of this area revealed shallow necrosis.

Under the conditions of this study, the test material was determined to be not irritating to the skin. I