2-piperazin-1-ylethylamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 2e: Meets generally accepted scientific standards, well-documented and acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Evaluation of skin sensitization and cross-reaction of nine alkyleneamines in the guinea pig maximization test.

Author:

Leung, H.W. and Auletta, C.S.

Year:

1997

Bibliographic source:

J Toxicol-Cut & Ocular Toxicol 16:189-195.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

study examined sensitization capability of structurally similar amines

Principles of method if other than guideline:

Magnusson, B. and Kligman, A.M.: The identification of contact allergens by animal assay. The guinea pig maximization test. J. Invest. Dermatol. 52:268, 1969

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A valid guinea pig maximisation test is available and therefore no in vitro test is necessary

Test material

Test material information

Constituent 1

Reference substance name:

2-piperazin-1-ylethylamine

EC Number:

205-411-0

EC Name:

2-piperazin-1-ylethylamine

Cas Number:

140-31-8

Molecular formula:

C6H15N3

IUPAC Name:

2-piperazin-1-ylethanamine

Details on test material:

Test material was obtained from Union Carbide. No additional information available.

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

Dunkin Hartley Haz:(DH)fBR albino guinea pigs (5-7 weeks old, 278-444 gr) were obtained from HRP Inc. (Denver, PA).

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal

Vehicle:

water

Challenge

Route:

epicutaneous, occlusive

Vehicle:

water

No. of animals per dose:

10/sex

Details on study design:

A range-finding study was conducted to select appropriate concentrations for the intradermal and epicutaneous procedures. Animals were inspected 24 and 48 hr after dosing for signs of necrosis and ulceration.

In the definitive sensitization test, groups of 10 male and 10 female guinea pigs each received 0.1 ml intradermal induction injections into 2 sites 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 saturation ((0.2 ml) 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 hr, 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 appropriate concentration of the test material 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 hr, and the sites inspected for signs of irritation 24-48 hr after removal of the occlusive dressings.

Seven days after the challenge exposure(i.e., 28 days from the start of the study), the cross-challenge treatment was administered. Test materials were administered to the clipped skin in a similar manner as in the challenge phase but at previously untreated sites (left flank). Smaller patches (0.825 in2 adhesive bandages) were used in order to allow all of the test materials to fit on the test site. Materials were applied to saturation (0.03 ml per patch). Patches were left in place for 24 hr and the sites inspected for signs of irritation 24-48 hr after removal of the occlusive dressings.

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. This allowed differentiation between primary skin irritation due to the test material, and those produced by a hypersensitivity reaction.

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

5

Total no. in group:

20

Clinical observations:

Clear dermal responses (scores of 1 or higher) 24 and/or 48 hours after challenge; six additional animals exhibited scores of 0.5 at one or both intervals. Based on clear responses in five of the twenty animals (25%)' A

Remarks on result:

positive indication of skin sensitisation

Results 2

Group:

positive control

Remarks on result:

not measured/tested

Results 3

Group:

negative control

Remarks on result:

other: Results not reported

Any other information on results incl. tables

Based on the probe study, the maximum concentrations used were 5% for the intradermal induction, 50% for epicutaneous induction and 25% for epicutaneous challenge phases. 

In the definitive study, five of 20 guinea pigs had a positive response. 

In the cross-reaction phase, animals induced with 50% demonstrated a greater response with diethylenetriamine (55%), hydroxyethylethylenediamine (75%), triethylenetetramine (45%) and piperazine (30%). Less of a response was observed in animals treated with ethylenediamine and tetraethylenepentamine (0 and 5% responded positive, respectively).

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Positive in guinea pig maximization test.

Positive results were also obtained in a cross challenge with several structurally similar alkyleneamines.

Executive summary:

The dermal sensitization potential was examined in the Guinea Pig Maximization Assay with aminoethylpiperazine (AEP). Cross-reactivity was also examined with structurally similar ethyleneamines. In this assay, AEP was positive and was shown to produce positive results when cross challenged with several structurally similar alkyleneamines.