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

Endpoint summary

Description of key information

 In a Local Lymph Node Assay (LLNA) in mice (CBA/Ca strain), according to a method equivalent to OECD Guideline 429 and SPL Standard Test method 595.12, T001141 is observed to be sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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

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

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)

Specific details on test material used for the study:

no data

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

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

Positive control results:

see 'Any other information on results incl. tables'

Parameter:

SI

Value:

2.83

Test group / Remarks:

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

Parameter:

SI

Value:

2.87

Test group / Remarks:

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

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

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)

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.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The skin sensitisation potential of T001141 was evaluated following topical application to the dorsal surface of the ear of CBA/Ca mice. Primary lymphocyte proliferation was assessed during the sensitising (induction) phase of the response. Following a preliminary sighting test at which there were no signs of systemic toxicity at a concentration of 5%, three groups, each of four animals, were treated with 50 μL of the test item (25 μL per ear) as a solution in dimethyl sulphoxide at concentrations of 1, 2.5 and 5% w/w in dimethyl sulphoxide. A further group of four animals was treated with dimethyl sulphoxide alone. The following stimulation index (SI) values were observed: at 1% concentration: 2.83, at 2.5%: 2.87 and at 5%: 3.04 (positive result as test to control ratio was greater than 3.0). Using the data generated, an EC3 value of 4.4% was calculated.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitisation:

The test item was considered to be a skin sensitiser under the conditions of the test. Using the data generated, an EC3 value of 4.4% was calculated. Based on these data and the criteria of the CLP Regulation (EC3 value > 2%), the substance is classified as skin sensitiser category 1B (H317: May cause an allergic skin reaction).

Respiratory sensitization:

No data were available to decide on the classification for respiratory sensitisation.