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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
From 23 October 1995 to 03 January 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the EU Method B.6 as well as in compliance with GLP.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Support for read-across can be obtained from the document "Category polyamines - 20170518.pdf" added to IUCLID Ch. 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Lot/batch No.: PN93-12
- Expiration date of the lot/batch: 21 September 1997
- Storage condition of test material: Room temperature in the dark
- Purity: 30.2%
- Physical state: A clear colourless liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England.
- Age at study initiation: Approx. 6-7 weeks
- Weight at study initiation: 270 to 315 g
- Housing: In groups of five in suspended metal cages with wire mesh floors
- Diet: A vitamin C enriched guinea-pig diet FD2, ad libitum.
- Water (e.g. ad libitum): Hay was given weekly.
- Acclimation period: 6 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approx. 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
a) for induction: 1% v/v (0.33% test substance) in distilled water
b) for challenge: 0.5% v/v (0.15% test substance) in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
a) for induction: 1% v/v (0.33% test substance) in distilled water
b) for challenge: 0.5% v/v (0.15% test substance) in distilled water
No. of animals per dose:
20 per group
Details on study design:
RANGE FINDING TESTS: The topical irritancy of a range of dilutions of the test substance was investigated. Based on the results of this study, 1% v/v concentration was chosen for induction and 0.5% v/v concentration was chosen for challenge. The former concentration was the concentration that produced some irritation but did not give rise to adverse effects, while the latter was the maximum concentration not giving rise to irritating effects.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 20 test animals
- Control group: 10 negative control animals
- Site: Left shoulder region, 20 x 20 mm
- Frequency of applications: Days 1, 8 and 15
- Duration: 2 weeks
- Concentrations: 1% v/v

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after final induction
- Exposure period: 6 h
- Test groups: 20 test animals
- Control group: 10 negative control animals
- Site: Right flank, 50 x 50 mm
- Concentrations: 0.5% v/v
- Evaluation (hr after challenge): 24 and 48 h after the removal of the patches

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.15%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.15%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Erythema, edema and dryness and sloughing of the epidermis.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.15%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.15%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Erythema, edema and dryness and sloughing of the epidermis.
Reading:
other: Both readings: 24 and 48 h
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
other: see Remark
Remarks:
Reading: other: Both readings: 24 and 48 h. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: Erythema, edema and dryness and sloughing of the epidermis.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the Buehler study, the test substance was not considered to be sensitising to the skin of guinea-pigs. Therefore, the test substance is not classified as sensitising to skin according to the criteria of EU CLP Regulation (1272/2008/EEC).
Executive summary:

A Buehler test was conducted to assess the contact hypersensitivity or sensitizing potential of N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine in guinea-pigs according to the EU Method B.6 and in compliance with GLP.

Twenty test and ten control animals were used. First the animals were exposed to three topical induction doses (on Days 1, 8, and 15) of 0.5 mL of the 1% v/v test substance (0.3% a.i.) saturated in 20 x 20 mm patch of surgical gauze (3 layers thick). The patch was sealed to the skin under a 5 cm strip of “Blenderm” covered by elastic adhesive bandage (“Elastoplast”) wound around the trunk and sealed with “Sleek”. Contact was maintained for approximately 6 h for each induction exposure and the reactions were noted 24 h after dressing removal. Control animals were treated similarly to test animals with the exception of test substance omission from the induction applications. Two weeks after the final induction the control and test animals were exposed to challenge doses of 0.5 mL of the 0.5% v/v test substance (0.15% a.i.) test substance for 6 h under similar occlusive conditions followed by evaluation after 24 and 48 h. Dermal reactions were scored on a numerical system for oedema and erythema. Evaluations were performed blind (i.e. the scorer had no knowledge of previous scores). The animals were observed daily for clinical signs of toxicity and the bodyweights were recorded on Day 1 (first day of topical application) and on the last day of observations for the challenge.

Localised dermal reactions were observed in 3/10 control animals at the 24-h observation and 1/10 control animals at the 48-h observation, consisting of varying dermal responses of erythema, oedema and dryness and sloughing of the epidermis. 5/20 test animals at the 24-h observation and 4/20 test animals at the 48-h observation exhibited very slight erythema with or without very slight oedema and dryness and sloughing of the epidermis. Two other test animals exhibited dryness and sloughing of the epidermis only, at the 48-h observation. Hence, it was concluded that none of the test animals showed a positive response.

Under the conditions of the Buehler study, the test substance was not considered to be sensitising to the skin of guinea-pigs. Therefore, the test substance is not classified as sensitising to skin according to the criteria of EU CLP Regulation (1272/2008/EEC).