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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo study already available
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to test guidelines and in accordance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dipropylentriamin
- Substance number: 95/420
- Physical state: liquid, achromatic
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Animal identification: ear tattoo
- Age at study initiation: young adult animals
- Weight at study initiation: Males: 3.03 - 3.13 kg; Female: 3.26 kg
- Housing: Single housing in stainless steel wire mesh cages with grating. No bedding in the cages, sawdust in the waste trays. Floor area: 3000 cm2
- Diet: About 130 g per animal per day (Kliba-Labordiaet 341, Klingentalmuehle AG Kaiseraugst, Switzerland)
- Water: About 250 mL tap water per animal per day.
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70%
- Air changes: Animals were housed in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12h/12h (6.00 AM - 6.00 PM - 6.00 AM)

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:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
3 minutes (animals 1-4) and 1 hour (animal 1 only)
Observation period:
animals 1 and 2: total 24 hours*
animals 3 and 4: total 72 hours*

*Studies were discontinued due to signs of severe irritation.

OBSERVATIONS:
A check for general observations and dead or moribund animals was made twice each workday and once on saturdays, sundays and on public holidays.
Number of animals:
1 female (animal No. 1) and 3 males (animal Nos 2-4)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Application site: Upper third of the back or flanks

REMOVAL OF TEST SUBSTANCE
- Washing: With Lutrol and with Lutrol/water (1:1)

SCORING SYSTEM:
according to guideline

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
- application for 3 minutes
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
4
Max. score:
4
Remarks on result:
other: At 1 and 24 hours after application full-thickness necrosis was recorded in 2/4 animals. At 48 and 72 hours full-thickness necrosis was seen in 2/4 animals and in 2/4 animals the study was discontinued due to severe irritation.
Irritation parameter:
edema score
Remarks:
- application for 3 minutes
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Remarks:
- application for 1 hour
Basis:
animal #1
Time point:
other: 1 and 24 hours
Score:
4
Max. score:
4
Remarks on result:
other: Full-thickness necrosis. After 24 hours the study was discontinued due to severe irritation.
Irritation parameter:
edema score
Remarks:
- application for 1 hour
Basis:
animal #1
Time point:
other: 1 and 24 hours
Score:
2
Max. score:
4

Any other information on results incl. tables

PATHOLOGICAL-ANATOMICAL AND HISTO-PATHOLOGICAL EVALUATION

Because the visual assessment of the skin did not allow a statement with respect to the depth of the necrotic changes observed (full-thickness necrosis), a cross incision of the treated skin was performed after the animals were sacrificed at study termination. Additionally, histo-pathological examination was performed in 3 animals. The classification of full-thickness necrosis was derived from these evaluations.

SURROUNDING SKIN

In those animals in which necrosis was observed, the surrounding skin was indexed as erythema=3

Applicant's summary and conclusion

Interpretation of results:
highly corrosive
Remarks:
Migrated information
Conclusions:
Under the test conditions choosen and considering the described findings, dipropylentriamine gives indication of causing full thickness destructio of skin tissue as a result of an exposure period of 3 minutes or 1 hour.
Executive summary:

The potential of the test substance to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of one white New Zealand rabbit for 3 minutes and 1 hour and to the intact skin of 3 white new zealand rabbits for 3 minutes. After the exposure period of 1 hour the following findings were observed: full thickness necrosis (observation period terminated after 24 hous). After the exposure period of 3 minutes the following findings were observed: erythema and edema, which were not reversibel within 24 hours after removal of the patch.

3 further animals exhibited visual necrosis 1 hour or 48 hours after removal of the patches. The observation period was terminated after 24 hours or 72 hours. The necrotic change of the skin of some animals (see results table) revealed a coagulative necrosis in the epidermis and dermis.