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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: weight of evidence of supporting substance (structural analogue)
Adequacy of study:
weight of evidence
Study period:
1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information on GLP

Data source

Reference
Reference Type:
publication
Title:
Evaluation of skin sensitization and cross-reaction of 9 alkyleneamines
Author:
Leung, H.W. et al.
Year:
1997
Bibliographic source:
J Toxicol Cut & Ocular Tox 16:189-195.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
According to Magnusson Kligman Assay
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted in 1997 by Leung et al. based on former standards. The study was conducted before the Local Lymph Node Assay was accepted as a OECD TG (first in 2002).

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Dunkin Hartley Haz:(DH)fBR albino guinea pigs
- Source: HRP Inc. (Denver, PA).
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 278-444 gr)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction 5%, Epicutaneous induction 10%, Epicutaneous challenge 5%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction 5%, Epicutaneous induction 10%, Epicutaneous challenge 5%
No. of animals per dose:
10 male and 10 female
Details on study design:
The maximization procedure involved the induction of an immunologically based sensitization process by injection of the test material into the skin (intradermal induction) followed by application of test material on the skin at the challenge site. Any of the observations greater than that seen in the irritation control animals was considered an allergic response.

Groups of 10 male and 10 female guinea pigs each received 0.1 mL intradermal induction injections into 2 sites each of the clipped shoulder skin as follows: 50% (v/v) Freund's complete adjuvant (FCA) water emulsion, the test material or vehicle, and the test material in FCA/water emulsion or FCA/water emulsion. Epicutaneous inductions were conducted 7 days later. The test material was applied to a 2 x 4 cm filter paper, which was then placed on the test site and secured with tape. The patches were left in place for 48 h, after which they were removed and the skin wiped free of any excess test material.
Epicutaneous challenge was undertaken by applying 2 x 2 cm filter paper squares soaked in the ethylenediamine solution to a previously untreated site (right flank) 14 days after epicutaneous induction (i.e., 21 days from the start of the study). Patches were left in place for 24 h, and the sites inspected for signs of irritation 24-48 h after removal of the occlusive dressings.

In general, scores of 1 or greater were considered clearly indicative of sensitization. Scores of 0.5 were considered equivocal, although a high percentage of 0.5 scores with no response in irritation control animals would be considered suggestive of sensitization. The percentage of animals reacting, rather than the intensity of reactions, was the criterion for assessing sensitization potency.

Grading scale used for evaluation of skin responses:
Score 0: No reaction
Score 0.5: Very slight (barely perceptible) erythema, usually nonconfluent
Score 1: Slight (well-defined) erythema
Score 2: Moderate erythema
Score 3: Severe erythema, with or without edema, necrosis, or eschar formation
Challenge controls:
Irritation control animals, five male and five female guinea pigs, received the same challenge procedures as in the definitive sensitization study, but did not have preceding intradermal and/or epicutaneous induction procedures
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Results
Reading:
other: 1st and 2nd reading
Hours after challenge:
2 448
Group:
test group
Dose level:
5%
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
45% in the group (n = 20) showed a positive skin response with score equal or greater than 1 at readings 24-48h after removal of the occlusive dressings.
Remarks on result:
other: see Remark
Remarks:
Reading: other: 1st and 2nd reading. . Hours after challenge: 2448.0. Group: test group. Dose level: 5%. No with. + reactions: 9.0. Total no. in groups: 20.0. Clinical observations: 45% in the group (n = 20) showed a positive skin response with score equal or greater than 1 at readings 24-48h after removal of the occlusive dressings..

Applicant's summary and conclusion