Trimethylenediamine

Skin sensitisation

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

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

Test material information

Constituent 1

Reference substance name:

Ethylenediamine

EC Number:

203-468-6

EC Name:

Ethylenediamine

Cas Number:

107-15-3

Molecular formula:

C2H8N2

IUPAC Name:

ethane-1,2-diamine

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)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Intradermal induction 5%, Epicutaneous induction 10%, Epicutaneous challenge 5%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

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 chemical

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..