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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1989-09-05 (J1) to 1990-02-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
validation of the test with positive controls is not reported
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shamrock Bio Service, 78950 Gambais, France
- Age at study initiation: no data
- Weight at study initiation: 323+/-10g (males) and 320+/-7g (females)
- Housing: individuallyin polycarbonate cage (48x27x20cm)
- Diet (e.g. ad libitum): ad libitum pelleted guinea pig diet "Maintenance guineapig reference 106" (UAR 91360 Villemoisson sur orge, France)
- Water (e.g. ad libitum): ad libitum drinking water filtered by 0.22µ membrane (Société Millipore, 78140 Vélizy, France)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 50+/-20%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 31-Aug-1989 (arrival) To: 29-Sept-1989 (necropsy)
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
intradermal induction: 0.1%
cutaneous induction: 10%
cutaneous challenge: 10%
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
intradermal induction: 0.1%
cutaneous induction: 10%
cutaneous challenge: 10%
No. of animals per dose:
control group 5 males and 5 females
treated group: 10 males and 10 females
Details on study design:
RANGE FINDING TESTS:
intradermal tests: 0.02% and 1%
cutaneous tests: 1% and 10%


MAIN STUDY
A. INDUCTION EXPOSURE

Intradermal induction D1
3injections on the scapular area:
0.1mL of Freund's complete adjuvant 50% in 0.9% NaCl
0.1mL of the test item 0.1% in water (treated group) or vehicle (control group)
0.1mL of a mixture 50/50 (V/V) of Freund complete adjuvant 50% in 0.9% NaCl and vehicle (for control group) or test item 0.1% in sterile water (for treated group)

Cutaneous induction D8
On day 7, the irritation created with the application of sodium Laurylsulfate 10% in vaseline.
On day 8, occlusive application on the scapular area of 0.5mL of the test item 10% (for treated group) or vehicle (for control group) for 48hours.


B. CHALLENGE EXPOSURE D22
On day 22, 24hours occlusive application on the scapular area of 0.5mL of the test item 10% on the right flank and 0.5mL of the vehicle on the left flank.
Reactions are evaluated 24 and 48 hours after removal of the dressing.
After the final scoring period, the animals were sacrificed and cutaneous samples were taken from the challenge application sites in all animals. Due to the presence of "doubtful" macroscopic cutaneous reactions, in 5 control animals and in 9 treated animals an histological examination was performed on tne cutaneous samples.
Positive control substance(s):
not specified
Positive control substance(s):
not specified
Positive control results:
No data
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
very slight eryhema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: very slight eryhema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
very erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: very erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
5/20:very slighy erythma; 4/20 important erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 9.0. Total no. in groups: 20.0. Clinical observations: 5/20:very slighy erythma; 4/20 important erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
4/20 very slight erythema; 4/20 important erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 8.0. Total no. in groups: 20.0. Clinical observations: 4/20 very slight erythema; 4/20 important erythema.

Group

Sex

Animal

24h

48h

Erythema

Oedema

Erythema

Oedema

LF

RF

LF

RF

LF

RF

LF

RF

Control

M

01

0

1

0

0

0

1

0

0

02

0

1

0

0

0

2

0

0

03

0

1

0

0

0

1

0

0

04

0

0

0

0

0

0

0

0

05

0

0

0

0

0

0

0

0

 

Control

F

16

0

1

0

0

0

1

0

0

17

0

2

0

0

0

2

0

0

18

0

0

0

0

0

0

0

0

19

0

0

0

0

0

0

0

0

20

0

0

0

0

0

0

0

0

 

Treated

M

06

0

1

0

0

0

1

0

0

07

0

0

0

0

0

0

0

0

08

0

3

0

0

0

3

0

0

09

0

1

0

0

0

2

0

0

10

0

3

0

0

0

3

0

0

11

0

0

0

0

0

0

0

0

12

0

1

0

0

0

1

0

0

13

0

3

0

0

0

3

0

0

14

0

0

0

0

0

0

0

0

15

0

0

0

0

0

0

0

0

 

Treated

F

21

0

0

0

0

0

0

0

0

22

0

0

0

0

0

0

0

0

23

0

1

0

0

0

1

0

0

24

0

0

0

0

0

0

0

0

25

0

0

0

0

0

0

0

0

26

0

3

0

0

0

3

0

0

27

0

1

0

0

0

0

0

0

28

0

0

0

0

0

0

0

0

29

0

0

0

0

0

0

0

0

30

0

0

0

0

0

0

0

0

 

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
DIPA at a concentration of 10% in water induced slight to marked cutaneous reactions as a result of irritant process in 5 control animals and 9 treated animals.
Executive summary:

The delayed contact hypersensivity of Diisopropylamine (DIPA) was evaluated in Guinea pigs according a protocol similar to OECD N°406 guideline (Magnusson and Kligman maximalisation test). The induction phase has been realized both by intradermal route on day 1 (DIPA 0.1% in water) and by cutaneous route on day 8 (DIPA 10%) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 20 by cutaneous application of DIPA 10%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase. After the challenge application, a very slight to well-defined erythema (scores of 1 and 2 in 5/10 control animals and in 5/20 treated animals) or moderate to severe erythema (score of 3 in 4/20 treated animals) were recorded. These reactions persisted at 48hours. The histological examination which was performed on the skin samples taken from the animals with cutaneous reactions, revealed the presence of slight to moderate lesions in the control and treated animals. These lesions consisted of an hyperkeratosis, acanthosis, mononuclear or polynuclear cell infiltration, haemorrhages, vascular ectasia and epidermic necrosis. The lesions were slightly more marked in the treated animals when compared to those noted in tne control animals. In the presence of a well-defined epidermic necrosis in the control animais and in the absence of an oedema or a spongiose in the treated animals, the cutaneous reactions which were recorded were considered as a result of an orthoergenic process of the test substance. Under these experimental conditions, DIPA at a concentration of 10% in water induced slight to marked cutaneous reactions as a result of irritant process in 5 control animals and 9 treated animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The delayed contact hypersensivity of Diisopropylamine (DIPA) was evaluated in Guinea pigs according a protocol similar to OECD N°406 guideline (Magnusson and Kligman maximalisation test) (Clouzeau, 1990). The induction phase has been realized both by intradermal route on day 1 (DIPA 0.1% in water) and by cutaneous route on day 8 (DIPA 10%) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 20 by cutaneous application of DIPA 10%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase. After the challenge application, a very slight to well-defined erythema (scores of 1 and 2 in 5/10 control animals and in 5/20 treated animals) or moderate to severe erythema (score of 3 in 4/20 treated animals) were recorded. These reactions persisted at 48hours. The histological examination which was performed on the skin samples taken from the animals with cutaneous reactions, revealed the presence of slight to moderate lesions in the control and treated animals. These lesions consisted of an hyperkeratosis, acanthosis, mononuclear or polynuclear cell infiltration, haemorrhages, vascular ectasia and epidermic necrosis. The lesions were slightly more marked in the treated animals when compared to those noted in tne control animals. In the presence of a well-defined epidermic necrosis in the control animals and in the absence of an oedema or a spongiose in the treated animals, the cutaneous reactions which were recorded were considered as a result of an orthoergenic process of the test substance.Under these experimental conditions, DIPA at a concentration of 10% in water induced slight to marked cutaneous reactions as a result of irritant process in 5 control animals and 9 treated animals.

The delayed contact hypersensivity of Diisopropylamine (DIPA) was evaluated in female CF-1 mice according to the mouse ear swelling test method (Celanese, 1987). The induction phase has been realized by cutaneous applications on the abdominal skin during 4 consecutive days with DIPA 5% v/v in ethanol in a group of 10 female mice. Appropriate positive (dinitrochlorobenzene DNCB) and negative (ethanol) control groups were used. The challenge phase was realized on day 10 by cutaneous application of 10µl DIPA on the left ear; a re-challenge application was realised at the same dose at day 17 on the right ear. Cutaneous reactions were scored 24 and 48 hours after the challenge and re-challenge phases. Measurements of ear thickness was realised after ether anaesthesia. There were no positive responders in the irritation control group. Animals challenged with DIPA exhibited no positive response at challenge or rechallenge in the test group. One of the five animals in the challenge irritation group exhibited a positive response, which was probably due to irritation. No positive response was exhibited in the rechallenge irritation control group. DIPA was considered as non-sensitizing in the Mouse Ear Swelling Test.


Migrated from Short description of key information:
DIPA is not found to be a sensitizer in the mouse ear swelling test and the guinea pig maximization assay.

Justification for selection of skin sensitisation endpoint:
Key study

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
No data available.

Justification for classification or non-classification

DIPA is not considered to be a skin sensitizer and is therefore not classified according to CLP criteria.