Registration Dossier

Administrative data

Description of key information

DIPA is corrosive for the skin and the eye and irritating for the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 - 25 Oct. 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
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: in house
- Age at study initiation: no data
- Weight at study initiation: 3.4 - 4.0 kg
- Housing: single, air-conditioned
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-2
- Humidity (%): 55 +-10
- Photoperiod (hrs dark / hrs light): 12 / 12


Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
3 min
Observation period:
30 - 60 min, 24, 48, 72 h, 7, and 14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5cm x 2.5 cm
- Type of wrap if used: adhesive patch + tissue bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 3 min

SCORING SYSTEM: Draize numerical scoring system.
Calculation of an average score over time (24, 48, and 72 h) and animals from individual effects values of erythema and edema separately as well as combined.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24-48-72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14d
Remarks on result:
other: necrosis
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24-48-72h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Remarks on result:
other: necrosis
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24-48-72h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Remarks on result:
other: necrosis
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24-48-72h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24-48-72h
Score:
0.67
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24-48-72h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritant / corrosive response data:
Clear evidence of necrosis:
Brown-red and brown-green discoloration of treated skin sites within 24 h, followed by dry and rough over time, associated with desquamation and/or open wound that ended in scar formation. The skin tissue became irreversibly damaged in total thickness.

Time 0,5 - 1h 24h 48h 72h 7d 14d
Animal 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3
Erythema 3 3 3 2 3 3 2 3 3 2 3 3 2 3 3  *  *  *
Oedema 1 1 1 1 1 1 1 1 1 1 0 1 2 2 1  *  *  *
Interpretation of results:
Category 1A (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
DIPA is considered as corrosive to rabbit skin.
Executive summary:

The acute dermal irritation of Diisopropylamine (DIPA) was evaluated in rabbits according to OECD 404 guideline and in compliance with the Good Laboratory Principles. DIPA was applied undiluted to the skin of 3 New-Zealand White albino rabbits and held in contact for 3 minutes by means of a semi-occlusive dressing. Animals were then observed daily until day 14.

Clear evidence of necrosis was observed within 24 h (brown-red and brown-green discoloration of treated skin sites), followed by dry and rough over time, associated with desquamation and/or open wound that ended in scar formation. The skin tissue became irreversibly damaged in total thickness.

Erythema mean scores over 24, 48 and 72 hours were 2, 3 and 3 for animals 1, 2 and 3 respectively.

Oedema mean scores over 24, 48 and 72 hours were 1, 0.67 and 1 for animals 1, 2 and 3 respectively. Skin damages were not reversible within the observation period.

Under these experimental conditions, DIPA is considered as corrosive to rabbit skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study report which meets generally accepted scientific principles. Study is well documented, before OECD TG and GLP existed. The study is fully sufficient for endpoint evaluation.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
; observation period was 8 days (OECD: 21)
GLP compliance:
no
Remarks:
; GLP was not compulsory at the time the study was conducted
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.10 kg, 3.44 kg, 3.3 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye of the same rabbit was untreated and served as control.
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
24 h; the substance was not washed out
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3 animals (2 males and 1 female)
Details on study design:
100 µl of the undiluted test substance was applied to the right conjuntival sac of one male and one female Vienna White rabbit. The left eye was left untreated and served as a control. The substance was not washed out.
Ocular reactions were recorded after 1, 24, 48 and 72 hours, as well as 6 and 8 days after instillation using a BASF-scoring system, which is convertible into the current OECD Draize scheme. For the evaluation, the BASF scores given in the raw data were converted to Draize scores. The reading time points used for assessment were 24, 48 and 72 hours after application.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-48-72 h
Max. score:
2
Remarks on result:
other: Not readable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
2.66
Max. score:
2
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
2.66
Max. score:
3
Reversibility:
not fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 d
Other effects:
Autopsy revealed the following findings: infestation with parasites in the liver and sanious rhinitis.

Individual scores for eye irritation of the animals treated with the test material for 24 h

 

24 h

48 h

Rabbit No.

1

2

3

1

2

3

Cornea

4

4

2

4

4

2

Iris

-

0

1

-

0

1

Conjunctiva redness

2 Na

2

2 Na

2 Na

2 Na

2 Na

Conjunctiva chemosis

2 B

2 B

2 B

3 B

3

2 B

 

72 h

8 d

Rabbit No.

1

2

3

1

2

3

Cornea

4

4

2

-

4

2

Iris

-

0

1

-

-

1

Conjunctiva redness

2 Na

2 Na

2 Na

-

-

2 Na

Conjunctiva chemosis

3 B

3

2 B

2

3

2

Na = cicatrice

B = blood

Discharge was seen at any reading time point.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Executive summary:

The potential of Diisopropylamine (DIPA) to induce ocular irritation was evaluated in rabbits according to a protocol similar to OECD 405 guideline. Hundred µl of the undiluted DIPA was applied to the right conjuntival sac to 3 Vienna White rabbits (2 males and 1 female) for 24 h; the substance was not washed out and the animals were observed during 8 days.

Corneal scores were 4, 4, 2 for animals 1, 2 and 3. Iris scores were 0 and 1 for animals 2 and 3 (animal 1 was unreadable). Conjunctivae scores were 2, 2, 2 for animals 1, 2 and 3. Chemosis scores were 2.66, 2.66, 2 for animals 1, 2 and 3.

Under these experimental conditions, DIPA was corrosive when administered by ocular route to rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

The acute dermal irritation of Diisopropylamine (DIPA) was evaluated in rabbits according to OECD 404 guideline and in compliance with the Good Laboratory Principles (Weigand and Rupprich, 1983). DIPA was applied undiluted to the skin of 3 New-Zealand White albino rabbits and held in contact for 3 minutes by means of a semi-occlusive dressing. Animals were then observed daily until day 14. Clear evidence of necrosis was observed within 24 h (brown-red and brown-green discoloration of treated skin sites), followed by dry and rough over time, associated with desquamation and/or open wound that ended in scar formation. The skin tissue became irreversibly damaged in total thickness. Erythema mean scores over 24, 48 and 72 hours were 2, 3 and 3 for animals 1, 2 and 3 respectively. Oedema mean scores over 24, 48 and 72 hours were 1, 0.67 and 1 for animals 1, 2 and 3 respectively. Skin damages were not reversible within the observation period. Under these experimental conditions, DIPA is considered as corrosive to rabbit skin.

In a BASF study (1977), diisopropylamine (DIPA) was evaluated in rabbits according to OECD 404 guideline with some deviations. DIPA (1 ml) was applied undiluted to the skin of 2 New-Zealand White albino rabbits and held in contact for 5 min, 2 h and 4 h by means of a semi-occlusive dressing. Animals were observed for 8 days. At 24 and 48 hours, both animals showed maximal erythema severe oedema scores (4/4 and 2/4 respectively) that were not fully reversible within 8 days for every exposure time. DIPA caused severe irreversible damage on the treated sites of the animals after an application time of 5 min, 2 hours as well as of 4 hours.

Eye irritation

The potential of Diisopropylamine (DIPA) to induce ocular irritation was evaluated in rabbits according to a protocol similar to OECD 405 guideline (BASF, 1977). Hundred µl of the undiluted DIPA was applied to the right conjuntival sac to 3 Vienna White rabbits (2 males and 1 female) for 24 h; the substance was not washed out and the animals were observed during 8 days. Corneal scores were 4, 4, 2 for animals 1, 2 and 3. Iris scores were 0 and 1 for animals 2 and 3 (animal 1 was unreadable). Conjunctivae scores were 2, 2, 2 for animals 1, 2 and 3. Chemosis scores were 2.66, 2.66, 2 for animals 1, 2 and 3.DIPA was corrosive when administered by ocular route to rabbits.

Respiratory irritation

Clinical and/or histological signs of respiratory tract irritation were observed in acute inhalation toxicity studies (BASF AG; 1979, Price et al., 1979; Gagnaire et al., 1989) and in repeated dose inhalation toxicity studies (Val Roloff, 1987; Zissu, 1995).

Justification for selection of skin irritation / corrosion endpoint:
Key study

Justification for selection of eye irritation endpoint:
Key study

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Skin irritation:

DIPA is corrosive to the rabbit skin after a 3-min exposure. On this basis and in accordance with Regulation (EC) No 1272/2008 DIPA was classified as corrosive to the skin category 1A (H314) and in accordance of Annex VI of Commission Directive 2001/59/EC, DIPA was classified corrosive to the skin (C, R35).

Eye irritation:

DIPA is corrosive to the rabbit eye. On the basis of this study and in accordance with Regulation (EC) No 1272/2008 DIPA was classified as irritating to eyes category 1 (H318).

Respiratory tract irritation:

Clinical and/or histological signs of respiratory tract irritation were observed in acute inhalation toxicity studies and in repeated dose inhalation toxicity studies. In accordance with Regulation (EC) No 1272/2008 DIPA was classified as Specific Target Organ Toxicity (STOT) Single Exposure (SE) Category 3 (H335) and in accordance with Annex VI of Commission Directive 2001/59/EC, DIPA was classified as irritant with the symbol Xi and the phrase R37 "irritating to the respiratory tract".