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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
xposure period was not 4 hours, but the test substance is corrosive

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(animals were used for a 3 minutes and 1 hour exposure; exposure period was not 4 hours, but the test substance is corrosive)
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1-ethylpiperazine
EC Number:
226-166-6
EC Name:
1-ethylpiperazine
Cas Number:
5308-25-8
Molecular formula:
C6H14N2
IUPAC Name:
1-ethylpiperazine
Details on test material:
- Name of test material (as cited in study report): Ethylpiperazin, Partie 6, Abl.Nr. 64-6112
- Analytical purity: 98%
- PSN 88/0569

Test animals

Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany (female rabbit) and Savo, med. Versuchstierzuchten, Kissling/Germany (males)
- Weight at study initiation: 2.77 kg (female), 2.3 kg (males)
- Housing: singly
- Diet: Kliba 341, about 130 g/animal/day
- Water: tap water, about 250 mL/animal/day
- Acclimation period: 8 days

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:
other: untreated skin sites of the same animal
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
3 minutes (right flank) and 1 hour (left flank)
Observation period:
72 hours
Number of animals:
1 female and 2 male animals
Details on study design:
TEST SITE
Clipping of the fur: at least 15 hours before the beginning of the study.
- Area of exposure: 2.5 x 2.5 cm, upper third of the back or flanks

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lutrol and lutrol/water (1:1)
- Time after start of exposure: at the end of the exposure period

SCORING SYSTEM:
based on J .H . Draize: Appraisal of the safety of chmemicals in foods, drugs and cosmetics. In dermal toxicity pp. 46 - 59, 1959 Austin, TEX.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 3 minutes exposure
Remarks on result:
other: superficial/medium thickness scabbing was observed but no necrosis
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 1 hour exposure
Reversibility:
not reversible
Remarks on result:
other: necrosis was observed immediately after exposure and during the whole observation period; full thickness necrosis was confirmed 72 hours after exposure at gross pathology
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-48-72 hours post treatment
Score:
3
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 3 minutes exposure; Erythema extending beyond the area of exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72 hours post treatment
Score:
1
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 3 minutes exposure; Edema extending beyond the area of exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-48-72 hours post treatment
Score:
3.7
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 1 hour exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72 hours post treatment
Score:
1.7
Max. score:
4
Reversibility:
no data
Remarks on result:
other: 1 hour exposure; Edema extending beyond the area of exposure
Irritant / corrosive response data:
3 minutes exposure:
Edema and erythema extending beyond the area of exposure and hemorrhage was observed in the male animals up to 24 hours after exposure. Superficial scabbing/medium thickness scabbing was additionally observed 72 hours post exposure in the male test animals.
1 hour exposure:
Edema extending beyond the area of exposure was observed in all test animals at any time post exposure. Necrosis was observed one hour after exposure up to 48 hours, resulting in full thickness necrosis after 72 hours in the male animals and superficial scabbing in the female animal. Findings were confirmed by gross pathology examination.

Any other information on results incl. tables

Table 1: Erythema and Edema scores of animals treated for 3 minutes with the unchanged test substance

Observation time

Animal

Erythema

Edema

 Add. information

3 minutes

1

2

0

 

 

2

2

2

 Edema and erythema extending beyond the area of exposure

 

3

4

0

 hemorrhage

24 hours

1

2

0

 

 

2

3

1

 Edema and erythema extending beyond the area of exposure

 

3

4

2

 hemorrhage

48 hours

1

3

0

 

 

2

4

1

 

 

3

3

2

 

72 hours

1

2

0

 

 

2

3

1

 Superficial scabbing

 

3

3

2

 Medium thickness scabbing

 Mean

 1

2.3

0

 

 

 2

3.3

1

 

 

 3

3.3

2

 

 Mean

 

3

1

 

Table 2: Erythema and Edema scores of animals treated for 1 hour with the unchanged test substance

Observation time

Animal

Erythema

Edema

Add. information

1 hour

1

3

1

 Edema extending beyond the area of exposure

 

2

4

3

Necrosis; Edema extending beyond the area of exposure

 

3

4

3

 Necrosis; Edema extending beyond the area of exposure

24 hours

1

3

2

Edema extending beyond the area of exposure

 

2

4

2

 Necrosis; Edema extending beyond the area of exposure

 

3

4

2

Necrosis; Edema extending beyond the area of exposure

48 hours

1

3

1

 Edema extending beyond the area of exposure

 

2

4

2

Necrosis; Edema extending beyond the area of exposure

 

3

4

2

 Necrosis; Edema extending beyond the area of exposure

72 hours

1

3

1

Superficial scabbing; Edema extending beyond the area of exposure

 

2

4

2

 Full thickness necrosis; Edema extending beyond the area of exposure

 

3

4

1

Full thickness necrosis; Edema extending beyond the area of exposure

 Mean

 1

3

1.3

 

 

 2

4

2

 

 

 3

4

1.7

 

 Mean

 

3.7

1.7

 

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria