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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
end: 2003-12-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, OECD N°406 Guideline (1992 July 17th)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
See other informations
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
the GPMT study was performed before implematation of the LLNA test

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyldiisopropylamine
EC Number:
230-392-0
EC Name:
Ethyldiisopropylamine
Cas Number:
7087-68-5
Molecular formula:
C8H19N
IUPAC Name:
ethylbis(propan-2-yl)amine
Details on test material:
- Name of test material (as cited in study report): Ethyldiisopropylamine
- Physical state: liquid
- Analytical purity: 99.65%
- Purity test date: 2002-10-09
- Lot/batch No.: JT010101
- Expiration date of the lot/batch: June 2004
- Stability under test conditions: no data
- Storage condition of test material: protected from moisture and at temperature<50°C

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hartley Crl: (HA) BR, caesarian obtanied, Barrier sustained - Virus Antibody Free (COBS - VAF) Charles River Laboratories France, L'arbresle, France
- Age at study initiation: 1-2 month old
- Weight at study initiation: 370+/-16g (males) 360+/-17g (females)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum 106 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water (e.g. ad libitum):ad libitum water filtered by a FG Millipore 0.22µ
- Acclimation period: at least 5 days before the beginning of the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal induction: corn oil. Cutaneous induction: 80/20 ethanol and purifies water. Cutaneous challenge: acetone
Concentration / amount:
1st induction (intradermal): 1%
2nd induction (cutaneous): 100%
Challenge(cutaneous): 5%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: intradermal induction: corn oil. Cutaneous induction: 80/20 ethanol and purifies water. Cutaneous challenge: acetone
Concentration / amount:
1st induction (intradermal): 1%
2nd induction (cutaneous): 100%
Challenge(cutaneous): 5%
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 route: Concentrations of 0.1%, 0.5%, 1%, 5%, 10%, and 25% were tested
Cutaneous route: concentrations of 10%, 25%, 50%, and 100% were tested
Challenge phase: Concentrations of 1%, 5%, 10%, 25%, 50% and 100% were tested

MAIN STUDY
INDUCTION PHASE
On day 1, three pairs of intradermal injections were performed in the interscapular region of all animals:
* Freund's complete adjuvant (FCA) diluted to 50% (v/v) with 0.9% NaCl (both groups),
* test item at the concentration of 1% (w/w) in corn oil (treated group) or vehicle alone (control group),
* test item at the concentration of 1% (w/w) in a mixture FCA/0.9% NaCl (50/50, w/w) (treated group) or vehicle at the concentration of 50% (v/w) in a mixture FCA/0.9% NaCl (50/50, v/v) (control group).

CHALLENGE PHASE
On day 7, a topical application of sodium lauryl sulfate at 10% (w/w) in vaseline was performed to the same area of the animals of both groups, in order to induce a local irritation.
On day 8, the animals of the treated group received a topical application of the undiluted test item to the same test site, which was then covered by an occlusive dressing for 48 hours. The animals of the control group received an application of ethanol/water (80/20, w/w) under the same experimental conditions.

On day 22, all animals of both groups were challenged by a cutaneous application of the test item at the concentration of 5% (w/w) in acetone to the right flank. The test item was maintained under an occlusive dressing for 24 hours. The vehicle was applied to the left flank under the same experimental conditions.
Mercaptobenzothiazole. 5control and 10 treated guinea pig. Intradermal induction (D1): 1%. Cutaneous induction (D8): 20%. Cutaneous challenge (D22): 20%
Positive control substance(s):
yes

Results and discussion

Positive control results:
Mercaptobenzothiazole at the concentration of 20% induced positive sensitisation reactions in 8/10 guinea pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to the maximization method of Magnusson and Kligman, Ethyldiisopropylamine does not induce delayed contact hypersensitivity in guinea pigs.
Executive summary:

The delayed contact hypersensivity of Ethyldiisopropylamine (EDIPA) was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test).

The induction phase has been realized both by intradermal route on day 1 (EDIPA 1% in vehicle) and by cutaneous route on day 8 (EDIPA 100%) 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 22 by cutaneous application of EDIPA 5%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase.

A discrete erythema (grade 1) was observed in 1/10 animals of the control group at the 24-hour reading. In the treated group, a discrete erythema (grade 1) was noted in 2/19 animals, at the 24-hour reading only.

In conclusion, in these experimental conditions, Ethyldiisopropylamine was not sensitizing in guinea pigs.