Reaction mass of 2-Piperazin-1-ylethanol and Piperazine-1,4-diethanol and Piperazine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication report which meets basic scientific principles. Piperazine is one constituent (ca. 15%) of the test substance.

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:

yes

Remarks:

no data on positive control substances

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Piperazine

EC Number:

203-808-3

EC Name:

Piperazine

Cas Number:

110-85-0

Molecular formula:

C4H10N2

IUPAC Name:

piperazine

Constituent 2

Reference substance name:

2-piperazin-1-ylethanol

EC Number:

203-142-3

EC Name:

2-piperazin-1-ylethanol

Cas Number:

103-76-4

Molecular formula:

C6H14N2O

IUPAC Name:

2-piperazin-1-ylethanol

Details on test material:

- Name of test materials (as cited in study report): Piperazine (PIP; CAS 110-85-0) and N-(2-hydroxy)ethylpiperazine (HEP; CAS 103-76-4)
- Analytical purity: no data

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: HRP Inc. (Denver, PA, USA)
- Age at study initiation: 5 - 7 weeks old
- Weight at study initiation: 278 - 444 g

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

PIP: Intradermal induction 5%, Epicutaneous induction 50%, Epicutaneous challenge 25%
HEP: Intradermal induction 5%, Epicutaneous induction 100%, Epicutaneous challenge 10%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

PIP: Intradermal induction 5%, Epicutaneous induction 50%, Epicutaneous challenge 25%
HEP: Intradermal induction 5%, Epicutaneous induction 100%, Epicutaneous challenge 10%

No. of animals per dose:

10 males and 10 females

Details on study design:

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 test material 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

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.

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

other: skin sensitisation response of PIP

Group:

test chemical

Dose level:

25%

No. with + reactions:

1

Total no. in group:

19

Clinical observations:

irritation score >= 1

Remarks on result:

other: Reading: other: skin sensitisation response of PIP. Group: test group. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 19.0. Clinical observations: irritation score >= 1.

Results 2

Reading:

other: skin sensitisation response of HEP

Group:

test chemical

Dose level:

100%

No. with + reactions:

2

Total no. in group:

20

Clinical observations:

irritation score >= 1

Remarks on result:

other: Reading: other: skin sensitisation response of HEP. Group: test group. Dose level: 100%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: irritation score >= 1.

Any other information on results incl. tables

Skin responses were evaluated and scored. 5% of animals tested with piperazin showed signs of sensitisation. 10% of animals tested with N-(2-hydroxy)ethylpiperazine showed sings of sensitisation.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information