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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
As the irritant/corrosive potential of the test substance was unknown one animal has been tested in a first step. As no severe skin damage has been noted in this animal, another two animals were tested. The results of the three animals were pooled for evaluation.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
N-(n-octyl)-2-pyrrolidinone
EC Number:
403-700-8
EC Name:
N-(n-octyl)-2-pyrrolidinone
Cas Number:
2687-94-7
Molecular formula:
C12 H23 N O
IUPAC Name:
N-(n-octyl)-2-pyrrolidinone
Details on test material:
- Name of test material (as cited in study report): N-(N-Octyl)pyrrolidone; Substance No. 91/453
- Physical state: colorless liquid
- Analytical purity: 99.3 %
- Lot/batch No.: 103/90
- Storage condition of test material: refrigerator

Test animals

Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler; D-W6050 Offenbach, FRG
- Age at study initiation: Young adult animais
- Weight at study initiation: 2.52-3.07 kg
- Housing: Single housing
- Diet: KLIBA Labordiät 341, 4 mm; Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland (about 130 g per animal per day)
- Water: About 250 ml tap water per animal per day
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
The test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 ml of the unchanged liquid test substance.
Duration of treatment / exposure:
4 hour(s)
Observation period:
15 days
Number of animals:
3
Details on study design:
The test substance was applied in a single dose to the intact untreated skin. The test patch was secured in position with a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lutrol concentrated and Lutrol diluted 1:1 with warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: (according to the OECD Draize system)
Erythema 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)

Edema formation:
0: No edema
1: Very slight edema (barely perceptible)
2: Slight edema (edges of area well defined by definite rising)
3: Moderate edema (raised approx. 1 mm)
4: Severe edema (raised more than 1 mm and extending beyond the area of exposure)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
1-3
Time point:
other: 24,48,72 hrs
Score:
3.2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
1-3
Time point:
other: 24, 48, 72 hrs
Score:
1.2
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
Haemorrhagia, spreading full-thickness necrosis (1 animal), scaling, highly superficial formation of eschar, spreading oedema.

Any other information on results incl. tables

 

Readings

Animal

Exposure period: 4 h

Erythema

Edema

Additional findings

1 h

1

1

0

 

2

2

2

HE+, ED+

3

2

1

HE

24 h

1

3

1

 

2

4

1

N+, ED+

3

2

1

HE

48 h

1

3

1

 

2

4

1

N+, ED+

3

3

2

HE

72 h

1

3

1

 

2

4

1

N+, *, ED+, SI

3

3

2

HE

8 d

1

1

0

SS

2

-

-

 

3

2

0

HE, SU

15 d

1

0

0

S

2

-

-

 

3

0

0

SU

Mean

24, 48, 72 h

1

3

1

 

2

4

1

 

3

2.7

1.7

 

Mean 24, 48, 72 h

1-3

3.2

1.2

 

Calculation of the mean according to 83/467/E EC Criteria of July 29th, 1983 (for calculation of the means of erythema and edema only the readings of 24, 48 and 72 hours are used).

 

HE: hemorrhage

HE+: hemorrhage extending beyond the area of exposure

ED+: edema extending beyond the area of exposure

N+: visual necrosis extending beyond the area of exposure

S: Scaling

SS: severe scaling

SU: superficial scabbing

*: Pathological evaluation (Dr. Freisberg): full thickness necrosis

SI: study already discontinued because of severe irritation

Visual necrosis was observed in one animal 72 hours after application. Thus, the observation period for this animal was terminated. The necrotic change of the skin was assessed by macroscopic pathology indicating full thickness necrosis. Such necroses are relevant for classification representing a chemical being corrosive to the skin.

Applicant's summary and conclusion