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Administrative data

Description of key information

In a key, reliable guinea pig maximisation test according to OECD Guideline 406 and EC method B.6, the test substance is observed to be not sensitising to skin (Rossbacher, 1993).

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:
July 14, 1992 - August 7, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was performed, before the LLNA was consdiered the default testing method for skin sensitisation potential.
Specific details on test material used for the study:
- Name of test material (as cited in study report): Bis-(-3-dimethylaminopropyl)-amin
- Substance type: liquid, slight yellowish
- Physical state: liquid
- Analytical purity: 99%
- Lot/batch No.: 19b/KW 23857369582-8
- Stability under test conditions: The stability of the test sustance in aqua bidest. has not been determined analytically. The homogeneity of the test substance preparation was provided by stirring (only mixture with Freund's adjuvant).
- Storage condition of test material: Room temperature
- Other: The storage stability of the test substance over the study period was guaranteed by reanalysis. The sample appeared to be homogeneous
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, D-W4323 Exertal 1, FRG
- Age at study initiation: Young adult animals
- Weight at study initiation: 292 - 341 g
- Housing: Makrolon, type IV cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days before the beginning of the study in the laboratory for dermal toxicity

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light ( 6.00 - 18.00 hours) 12 hours darkness (18.00 - 6.00 hours)
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.1% test substance in 0.9% aqueous NaCl solution or in Freund's adjuvant/0.9% aqueous NaCl solution (1:1) or 0.9% aqueous NaCl solution
Percutaneous induction: test substance 1% in aqua bidestilled
Challenge: test sbustance 0.5% in aqua bidest.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.1% test substance in 0.9% aqueous NaCl solution or in Freund's adjuvant/0.9% aqueous NaCl solution (1:1) or 0.9% aqueous NaCl solution
Percutaneous induction: test substance 1% in aqua bidestilled
Challenge: test sbustance 0.5% in aqua bidest.
No. of animals per dose:
Number of animals per control group: 5
Number of animals of the test group: 10
Details on study design:
RANGE FINDING TESTS:
Amount applied:
2x2 cm filter paper strips were applied to the skin of the flanks under an occlusive dressing (the bandage consists of rubberized linenpatches 4x4 cm (adhesive fleece)). The test filter paper strip was soaked in the test substance formulation; thus, the animals were exposed to about 0.15 g of the test substance formulation.
Exposure period:
The test substance was applied 2 times for 24 hours with - in a period of 96 hours in order to detect non-specific phenomena that are not caused by a sensitization reaction but could possibly be attributed to a shift in the irritation threshold.
Site of application: flank, respective on the same area
Number of test animals: 4 per test concentration
Readings: about 24 and 48 hours after the beginning of application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: intradermal induction: 6 intradermal injections in groups of two per animal
Injections for the test groups:
A) front row: 2 injections each of 0.1 mL Freund's adjuvant without test substance emulsified with 0.9% aqueous NaCl-solution in a ratio of 1:1
B) middle row: 2 injections each of 0.1 mL of the test substance formulation
C back row: 2 injections each of 0.1 mL Freund's adjuvant/0.9% aqueous NaCl solution (1:1) with test substance
Injections for control groups 1 and 2:
The animals were given the same injections (A, B, C) but without test substance, only with the formulating agent
Site of application: shoulder
Readings: 24h after the beginning of application
Percutaneous induction:
Percutaneous induction was carried out one week after intradermal induction.
Amount applied:
2 x 4 cm filter paper strips were applied to the skin of the shoulder under an occlusive dressing (the bandage consists of rubberized linenpatches 4x6 cm (adhesive fleece)). The filter paper strip was soaked in the test substance formulation; thus, the animals were exposed to about 0.3 g of the test substance formulation.
The control animals were not treated since the distilled water used as formulating agent was not expected to influence the result of the study.
Duration of exposure: 48 hours
Site of application: shoulder, same area as in the case of the previous intradermal application
Readings: 48 hours after the beginning of application
Assessment of skin findings: analogous to the pretest

B. CHALLENGE EXPOSURE
Test concentration: non-irritant concentration
Challenge 21 days after intradermal induction
Amount applied:
2x2 cm filter paper strips were applied to the skin of the flank under an occlusive dressing (the bandage consists of rubberized linenpatches 4x4 cm (adhesive fleece)). The test filter paper strip was soaked in the test substance formulation: thus the animals were exposed to about 0.15 g of the test substance formulation.
- treatment of the test group with the test substance formulation
Duration of exposure: 24 hours
Site of application: intact flank
Readings: 24 and 48 hours after the removal of the patch
Assessment of skin findings: analogous to the pretest
Challenge controls:
Treatment of control group 1 with the test substance formulation; control group 2 remained untreated
Positive control substance(s):
yes
Remarks:
1-chlor-2,4-dinitro-benzol
Positive control results:
The positive control with 1-chlor-2,4-dinitro-benzol showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5% in aqua bidest.
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no skin reactions
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5% in aqua bidest.
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no skin reactions
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5% in aqua bidest.
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reactions
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5% in aqua bidest.
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reactions
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
positive control substance in 1% ethanol
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate to severe erythema and very slight edema in 2 out of 20 test group animals; 14 out of 20 animals of the test group showed well-defined erythema, 11 of them additionally exhibited very slight edema; very slight erythema in 4/20 test group animals

After the intradermal induction well-defined erythema and slight edema were observed at the injection sites of the control group animals and test group animals at which only Freund's adjuvant/0.9% aqueous NaCl-solution (1:1) was applied. Injection of the test substance in 0.9% aqueous NaCl-solution caused well-defined erythema and very slight edema in the animals of the test group. After application of the test substance preparation in Freund's adjuvant/0.9% aqueous NaCl-solution (1:1) well-defined erythema and slight edema could be observed in the test group animals.

The control group animals which were treated with 0.9% aqueous NaCl-solution did not show any skin reactions.

The percutaneous induction was only carried out in the test group because with aqua bidest. a vehicle was used, that was not expected to influence the result of the study.

Incrustation, partially open (caused by the intradermal induction) in addition to well-defined erythema and slight edema could be observed.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the study under the test conditions chosen and taking the above cited evaluation criteria into account , the test substance does not have a sensitising effect on the skin of the guinea pig in the maximization test. The substance is not to be classified according to CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation - in vivo:

In a Klimisch 1-rated guinea-pig maximisation test (Rossbacher, 1993; according to OECD guideline 406), 10 females were first induced intradermally with 0.1% test substance in 0.9% aqueous NaCl solution or in Freund's adjuvant/0.9% aqueous NaCl solution (1:1) or 0.9% aqueous NaCl solution. Seven days later the animals were topically induced with an occlusive dressing containing 1% v/v test substance in distilled water. The control animals were not treated since the distilled water used as formulating agent was not expected to influence the result of the study. On day 22, all animals were challenged by occluded application of 0.5% v/v test substance in distilled water. Challenge application of the 0.5% test substance in distilled water caused no skin reaction in any of the test group animals 24 and 48 hours after challenge.

Challenge application of the 0.5% test substance in the negative control group caused no skin reactions in any of the control animals. Challenge application of the positive control substance in 1% ethanol caused moderate to severe erythema and very slight edema in 2 out of 20 test group animals; 14 out of 20 animals of the test group showed well-defined erythema, 11 of them additionally exhibited very slight edema; very slight erythema in 4/20 test group animals.

Based on the results of the study under the test conditions, the test substance does not have a sensitizing effect on the skin of the guinea pig in the maximization test.

Skin sensitisation - in vitro:

An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (initiated before October 11th, 2016) are available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the criteria of the CLP Regulation, the test substance should not be classified as sensitising to the skin. No data on respiratory sensitisation is available.