3,3'-iminodi(propylamine)

Skin irritation / corrosion

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-iminodi(propylamine)

EC Number:

200-261-2

EC Name:

3,3'-iminodi(propylamine)

Cas Number:

56-18-8

Molecular formula:

C6H17N3

IUPAC Name:

bis(3-aminopropyl)amine

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 or test system 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

Results

Results 1

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.

Results 2

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

Results 3

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.

Results 4

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.