Registration Dossier

Administrative data

Description of key information

A single 3-minute application of undiluted dipropylenetriamine to the skin of rabbits caused corrosion observable from 1 hour after application. A single application of undiluted dipropylenetriamine to the rabbit eye caused corrosion with severe corneal opacity and severe ulceration from day 3 onwards. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
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)
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
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

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

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
in vivo study already available
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Method according to the Federal Register, Vol . 38, No. 187 (27.09.73), § 1500 .42 and Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, Austin, Texas 1959, p .51
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: M. GAUKLER (6050 Offenbach)
- Weight at study initiation: 2.56 kg
- Diet: Ssniff K, standard diet for rabbits and guinea pigs (INTERMAST GMBH, Soest), ad libitum
- Water: ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 µl
Duration of treatment / exposure:
single application
Observation period (in vivo):
8 d
Number of animals or in vitro replicates:
6 (3 males, 3 females)
Details on study design:
SCORING SYSTEM: Follows OECD guideline 405
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 8 d
Score:
3 - 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: opacity of the cornea could not be scored after 72 h due to severe ulcerations
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h -8 d
Score:
0 - 1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: changes in the iris could not be scored after 72 h due to severe ulcerations
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h - 8d
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: redness of the conjuctivae could not be scored after 72 h due to severe ulcerations
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 8 d
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
In 2 out of 6 animals after 72 h and all animals after 8 d severe ulcerations were observed. Further oberservations were: grey/white nictating membrane, sticky eyes, severe suppuration, grey/white mucous membrane, blood.
Interpretation of results:
corrosive
Remarks:
Migrated information
Conclusions:
Based on the findings of the study Dipropylenetriamine was judged corrosive to the eyes.
Executive summary:

Dipropylenetriamine was applied to conjunctival sac of the eyes of 6 Vienna White rabbits. Animals were observed after 24, 48 and 72 hours and up to 8 days after the treatment. The application caused corrosion (irreversible), predominantly expressed by severe corneal opacity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

In a skin irritation test according to OECD guideline 404, the test substance was applied undiluted to the skin of New Zealand White rabbits for 3 minutes and 1 hour under semi-occlusive conditions (BASF AG, 1996). Observations took place 1, 24, 48 and 72 hours post-treatment. Full-thickness necrosis was observed in 2/4 animals at 1 and 24 hours after application and in 2/4 animals at 48 and 72 hours after application. Slight edema was seen in all animals. For 2/4 animals the study was discontinued after 24 hours due to signs of severe irritation/corrosion. For the same reasons the test was stopped after 72 hours for the remaining 2 animals. Dipropylenetriamine was judged highly corrosive to the skin.

In another study, four Vienna White rabbits were exposed to dipropylenetriamine under occlusive conditions for 3 minutes or 1 hour, followed by an 8-day observation period (BASF AG, 1978). Necrosis and parchment/leatherlike skin developed and remained throughout the 8-day observation period.Slight edema was seen in all animals.Dipropylenetriamine was judged highly corrosive to the skin.

 

Eye irritation

Dipropylenetriamine was applied to conjunctival sac of the eyes of 6 Vienna White rabbits (BASF AG, 1978c). Animals were observed after 24, 48 and 72 hours and up to 8 days after the treatment. The application caused corrosion (irreversible), predominantly expressed by severe corneal opacity. Dipropylenetriamine was judged corrosive to the eyes.

Dipropylenetriamine was applied to the conjunctival sac of the eyes of 2 rabbits (BASF AG, 1956). Application of the pure substance caused strong redness paired with necrosis, swelling, opacity and inflammation. Application of a 10% aqueous solution with pH 10 caused clear redness and swelling, while application of a 10% aqueous solution with pH 7 did not cause irritation. Dipropylenetriamine was judged corrosive to the eyes.

 

Respiratory irritation

It is a reasonable assumption that corrosive substances may also cause respiratory tract irritation (RTI) when inhaled at exposure concentrations below those causing frank respiratory tract corrosion. There is evidence from the acute inhalation toxicity study in animals that such an irritation might occur.

As in general a classification for corrosivity is considered to implicitly cover the potential to cause RTI an additional STOT-SE Category 3 classification is considered to be superfluous (according to ‘Guidance on the Application of the CLP Criteria’, Version 3.0, ECHA-12-G-14-EN - November 2012).

 

 

 


Justification for selection of skin irritation / corrosion endpoint:
Reliable guideline compliant study.

Justification for selection of eye irritation endpoint:
Reliable guideline compliant study.

Effects on skin irritation/corrosion: highly corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Dipropylenetriamine is included in Annex VI of Regulation 1272/2008/EC with the following classification:

Table 3.1: corrosive to skin: cat. 1A

Table 3.2: R35

Based on the available data, dipropylenetriamine needs to be classified as corrosive to the skin and eyes according to Directive 67/548/EEC (C, R35) and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 (Category 1A, H314: Causes severe skin burns and eye damage).