1-acetyl-4-(4-hydroxyphenyl)piperazine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-02-23 to 2004-03-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

: Insufficient information on the test substance, test animals, methodological details and information on results presented

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: SPL Standard Test method 595.12

Principles of method if other than guideline:

not applicable

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme but no formal claim of GLP compliance is made for this study.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

1-acetyl-4-(4-hydroxyphenyl)piperazine

EC Number:

267-744-8

EC Name:

1-acetyl-4-(4-hydroxyphenyl)piperazine

Cas Number:

67914-60-7

Molecular formula:

C12H16N2O2

IUPAC Name:

1-acetyl-4-(4-hydroxyphenyl)piperazine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material: JNJ-119379-AAA (T001141)
- Physical state: solid (powder)
- Appearance: white powder

Specific details on test material used for the study:

no data

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (deg C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

as a solution at 1, 2.5 and 5% (w/w) in dimethylformamide
a further group of 4 animals was treated with dimethyl formamide alone

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: no data
- Systemic toxicity: no signs of systemic toxicity at a concentration of 5% w/w in dimethyl formamide
- Ear thickness measurements: no data
- Erythema scores: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: A stimulation index of 3.0 or greater indicates a positive result.

TREATMENT PREPARATION AND ADMINISTRATION:
- Three groups, each of four animals were treated with 50 µL (25 µL per ear) of the test substance as a solution in dimethylformamide.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

other: 2,4-dinitrobenzenesulfonic acid, sodium salt; 1%,10%,20% v/v in 1% pluronic F-68 in distilled water

Statistics:

no data

Results and discussion

Positive control results:

see 'Any other information on results incl. tables'

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

2.83

Test group / Remarks:

based on 4 animals of 1% (w/w) group in dimethyl formamide

Results 2

Parameter:

SI

Value:

2.87

Test group / Remarks:

based on 4 animals of 2.5% (w/w) group in dimethyl formamide

Results 3

Parameter:

SI

Value:

3.04

Test group / Remarks:

based on 4 animals of 5% (w/w) group in dimethyl formamide

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
no data

DETAILS ON STIMULATION INDEX CALCULATION
The Stimulation Index (SI) was expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group

EC3 CALCULATION
Using the data generated, an EC3 value of 4.4% was calculated.

CLINICAL OBSERVATIONS:
no data

BODY WEIGHTS
no data

Any other information on results incl. tables

Using the data generated, an EC3 value of 4.4% was calculated.

Positive Control Local Lymph Node Assay in the Mouse (2004)

Project Number	Start Date	Finish Date	Test Material	Concentration	Vehicle	Stimulation Index^a	Classification^b
039/687·	29/04/2004	05/05/2004	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	1.40, 2.23, 6.09	Positive
039/688*	29/04/2004	05/05/2004	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	1.74, 2.20, 8.89	Positive
039/719*	14/10/2004	26/10/2004	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	tetrahydrofuran	1.97, 3.71, 7.82	Positive
039/720*	29/09/2004	05/10/2004	2,4‑Dinitrobenzenesulfonic acid, sodium salt	1%, 10%, 20% v/v	1% pluronic F-68 in distilled water	1.03, 4.41, 13.55	Positive
039/723*	27/10/2004	02/11/2004	α‑Hexylcinnamaldehyde, tech., 85%	10%, 25%, 50% v/v	cottonseed oil	1.52, 2.63, 5.07	Positive

 

a=         Ratio of test to control lymphocyte proliferation

b=         Stimulation index greater than 3.0 indicates a positive result

* =         Standard Test Method 595 (Pooled nodes)

·=          Standard Test Method 599 (Individual nodes)

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The test substance was considered to be a sensitiser under the conditions of the test. Based on these data and the criteria of the CLP regulation (EC3 value >2%), the test item is classified as a skin sensitiser category 1B.