Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18.03-10.06.1992
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no necropsy was performed
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): t-Butylamine, ZST-No. 92/18
- Physical state: liquid, colourless
- Analytical purity: 99.9 %
- Expiration date of substance: November 1993
- Stability under test conditions: 2-10°C, under N2
- Storage condition of test material:
- Other:

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd .CH-4414 Füllinsdorf
- Age at study initiation: 13 weeks
- Weight at study initiation: male : 2.7 kg; females : 2.6 - 2.7 kg
- Housing: Individually in stainless steel cages (size : 86 x 54 x 33 cm) equipped with feed hoppers and drinking water bottles.
- Diet: Pelleted standard Kliba 341, Batch 66/91 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum .
- Water: Community tap water from Füllinsdorf, ad libitum .
- Acclimation period: days under test conditions after veterinary examination .


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- 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:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
3 min
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm). The skin of the animals was examined once, 1 day prior to test article administration.
Only those animals with no signs of skin injury or irritation were used in the test.

On test day 1, 0.5 ml of the test article was applied to approx. 6 cm² of the intact skin of the clipped area. It was covered with a 3 .0 cm x 3 .0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The duration of treatment was 3 minutes. Then the dressing was removed and the skin was flushed with lukewarm-tap water to remove excess test article.

Prior to test article application the animals were sedated with an intramuscular injection of XYLAPAN (0 .25 ml/kg) for ethical reason.
SCORING SYSTEM:
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)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Irritation:
t-Butylamine showed a primary irritation score of 4 .0 (max . 8 .0 erythema/edema scoring) when applied to healthy intact rabbit skin . Local signs (mean values from 3 minutes to 72 hours) consisted of grade 3.7 erythema and grade 0.4 edema. They were not reversible until day of experimental termination.

Corrosion:
Starting within 1 hour after the 3 minutes treatment necroses with full skin thickness destructions were observed. These effects increased until the 24 hour observation were additionally 1 out of 3 animals showed fissures. The necroses described were well movable and the edges protruded. No effect of recovery of local findings was observed during the 72 hours observation period.

Any other information on results incl. tables

Clinical signs and mortality:

No systemic symptoms were observed in the animals during the test and observation period, and no mortality occurred.

Body weight:

The body weight gain of all rabbits was with the normal range of variability.

Detailled skin irritation and corrosion data:

Animal No. 1, MALE

After 3 minutes: Application area: moderate to severe erythema, whole area treated.

After 1 hour: Application area: moderate to severe erythema, whole area treated; necroses observed.

After 4 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in-depth); necroses observed; necroses hardened and therefore well movable.

After 24 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in-depth); necroses observed; necroses hardened an d therefore well movable.

After 48 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in-depth); necroses observed; necroses hardened and therefore well movable.

After 72 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in-depth); necroses observed; hardened, well movable; edges of the necroses protruded.

Animal No. 2, FEMALE

After 3 minutes: Application area: moderate to severe erythema, whole area treated; very slight edema whole area treated.

After 1 hour: Application area: moderate to severe erythema, whole area treated; very slight edema whole area treated; necroses observed.

After 4 hours: Application area: severe erythema (beet redness) to slight eschar formation (injury in depth); necroses with crusts, slightly hardened and movable; slight edema, edges of area well defined by definite rising. After 24 hours: Application area: severe erythema (beet redness) to slight eschar formation (injury in depth); necroses, size: 2 x 0.5 cm, slightly hardened and movable .

After 48 hours: Application area: severe erythema ( beet redness) to slight eschar formation (injury in depth); necroses, size: 2 x 0.5 cm, slightly hardened and movable, edges of the necroses protruded.

After 72 hours: Application area: severe erythema ( beet redness) to slight eschar formation (injury in depth); necroses, size: 2 x 0 .5 cm, slightly hardened and movable, edges of the necroses protruded.

Animal No. 3, FEMALE

After 3 minutes: Application area: moderate to severe erythema, whole area treated; moderate edema (raised approx. 1 mm)/whole area; necroses observed.

After 1 hour: Application area: moderate to severe erythema, whole area treated; necroses observed.

After 4 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in depth), whole area; necroses, slightly hardened and movable.

After 24 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in depth), whole area; necroses with fissures, well movable, edges protruded.

After 48 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in depth), whole area; necroses with fissures, well movable, edges protruded.

After 72 hours: Application area: severe erythema (beet redness) to slight eschar formations (injury in depth), whole area; necroses with fissures, well movable, edges protruded.

Readings

Animal

Exposure period:3min

Erythema

Edema

Additional findings

3 min

1

3

0

 

2

3

1

 

3

3

3

 

1 h

1

3

0

 

2

3

1

 

3

3

0

 

4 h

1

4

0

 

2

4

2

 

3

4

0

 

24 h

1

4

0

 

2

4

0

 

3

4

0

 

48 h

1

4

0

 

2

4

0

 

3

4

0

 

72 h

1

4

0

 

2

4

0

 

3

4

0

 

Mean

24, 48, 72 h

1

4

0

 

2

4

0

 

3

4

0

 

Mean 24, 48, 72 h

1-3

4

0

 

Applicant's summary and conclusion