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Toxicological information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (BASF AG).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The guinea pig maximisation test was performed in accordance to the OECD guideline 406 and can be considered as a validated and reliable testing method for skin sensitization including a high statistical sample size and the challenge phase.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Neutrol TE
- Physical state: liquid
- Analytical purity: 88.4 %
- Composition of test material, percentage of components: EDA + 3PO, 7.75 %; EDA + 4PO, 88.4 %; EDA + 4PO, 3.35 %
- Lot/batch No.: 36-3224
- Stability under test conditions: tested at completion of all tests
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White, Dunkin-Hartley HOE DHPK [SPF-LAC] BÖ
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co KG, Extertal, Germany
- Weight at study initiation: 250 - 291 g
- Housing: 5/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: 5 % (±FCA); epicutaneous induction: 50 % (corresponding to 0.3 g test substance); 1. Challenge: 25 % (corresponding to 0.15 g test substance); 2. Challenge: 25 % (corresponding to 0.15 g test substance)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: 5 % (±FCA); epicutaneous induction: 50 % (corresponding to 0.3 g test substance); 1. Challenge: 25 % (corresponding to 0.15 g test substance); 2. Challenge: 25 % (corresponding to 0.15 g test substance)
No. of animals per dose:
Controls: 10; Test group: 20
Details on study design:
RANGE FINDING TESTS:
Test substance was applied epicutaneously to the flank 2 times for 24 hours under occlusive dressing in a 96 hour period , readings were performed at 24 and 48 hours after beginning of the application (number of test animals: 3 resp. 4 per concentration). The minimum irritant concentration was found to be a 50 % aqueous test substance preparation and the maximum non-irritant concentration a 25 % aqueous test substance preparation .
Applicability : it was possible to inject a 5 % test substance preparation in aqua dest . resp. in Freund's adjuvant/ aqua dest . (1 : 1) with a syringe .

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1. exposure: injection; 2. exposure: epicutaneous occlusive 48 hours
- Test groups: 1. exposure: A: FCA/water; B: water + 5 % TS; C: FCA/ water + 5 % TS; 2. exposure: 50 % TS
- Control group: 1. exposure: A: FCA/water; B: water; C: FCA/water; 2. exposure: untreated (water would not be considered to cause any effects)
- Site: shoulder, 3 rows of injections (A, B, C)


B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 14; 21
- Exposure period: 24 hours
- Test groups: 1. challenge: 25 % TS; 2. challenge: 25 % TS
- Control group: group 1: 1. challenge 25 % TS, 2. challenge 25 % TS; group 2: untreated, 2. challenge 25 % TS
- Site: Intact clipped flank: 1. challenge: right flank 25 % TS; 2. challenge: left flank 25 % TS
- Evaluation (hours after challenge): 24, 48, 72 hours after the beginning of the application
Challenge controls:
Not necessary, control groups were without response after challenge.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
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: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 2nd negative control
Dose level:
water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
other: 2nd negative control
Dose level:
water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
very slight erythema (barely perceptible)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: very slight erythema (barely perceptible).
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading:
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: 2nd negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group:
Reading:
rechallenge
Hours after challenge:
72
Group:
other: 2nd negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group:
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Applicant's summary and conclusion