N-ethyl-N-(3-methylphenyl)propionamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 June to 1 July 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-ethyl-N-(3-methylphenyl)propionamide

EC Number:

423-640-6

EC Name:

N-ethyl-N-(3-methylphenyl)propionamide

Cas Number:

179911-08-1

Molecular formula:

C12H17NO

IUPAC Name:

N-ethyl-N-(3-methylphenyl)propanamide

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, England
- Age at study initiation: 14 to 16 weeks
- Weight at study initiation: 3.2 to 3.6 kg
- Housing: individually in metal cages with perforated floors in Building R14 Room 3
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: acclimatised to the experimental environment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 19 air changes per hour
- Photoperiod (hrs dark / hrs light): give 12 hours of artificial light (07:00 - 19:00 hours) in each 24 hours period

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Amount: 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 25 mm x 25 mm
- A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water (30° to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
Examination of the treated skin was made on Day 1 (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made on Days 5 through 14.

SCORING SYSTEM:
- Method of calculation:
Local dermal irritation was assessed using the prescribed numerical system:
Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 3
preventing erythema reading 4

Oedema formation:

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 2945

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible within: day 10

Results 2

Irritation parameter:

edema score

Basis:

animal: 2945

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal: 2946

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Results 4

Irritation parameter:

edema score

Basis:

animal: 2946

Time point:

24/48/72 h

Score:

0.333

Max. score:

4

Reversibility:

fully reversible within: Day 3

Results 5

Irritation parameter:

erythema score

Basis:

animal: 2947

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Results 6

Irritation parameter:

edema score

Basis:

animal: 2947

Time point:

24/48/72 h

Score:

1.333

Max. score:

4

Reversibility:

fully reversible within: Day 6

Irritant / corrosive response data:

Very slight to well-defined erythema with or without slight oedema developed in all animals during the 24 hours following application of the test material. These reactions persisted in all animals during the first week of the study, resolving in one animal by Day 10 but persisting in two rabbits to study termination on Day 14. In addition, desquamation (characterised by dryness/sloughing) was observed in two animals from Day 6 through Day 13 and 14 respectively.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

A single semi-occlusive application of the test item to intact rabbit skin for four hours elicited well­ defined dermal irritation.

Executive summary:

A study was performed to assess the skin irritation potential of the test item to the rabbit. The method followed was that described in EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (skin irritation).

 

Three rabbits were each administered a single dermal dose of 0.5ml of the test substance and observed for 14 days.

 

A single semi-occlusive application of the test item to intact rabbit skin for four hours elicited well­ defined dermal irritation. Reactions had resolved in one animal by Day 10 but persisted at study termination on Day 14 in two rabbits.

 

The test item will require labelling with the risk phrase R38 "Irritating to skin" in accordance with Commission Directive 93/21/EEC.