4-bromo-2,2-diphenylbutanenitrile

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 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:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: SPL Standard Test Method 595.12

Deviations:

no

GLP compliance:

no

Remarks:

This study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

4-bromo-2,2-diphenylbutanenitrile

EC Number:

254-337-5

EC Name:

4-bromo-2,2-diphenylbutanenitrile

Cas Number:

39186-58-8

Molecular formula:

C16H14BrN

IUPAC Name:

4-bromo-2,2-diphenylbutanenitrile

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-1597622-AAA (T000625)
- Physical state: solid (powder)
- Appearance: White powder

Specific details on test material used for the study:

No further details available

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

No data

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

0 (vehicle alone), 5, 10, and 25 % w/w

No. of animals per dose:

4 animals per dose group

Details on study design:

RANGE FINDING TESTS: Preliminary sighting tests were performed at concentrations of 25 and 50 % w/w. No details on the results were provided in the study report.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay - The assay determined the level of lymphocyte proliferation in lymph nodes draining the application site of the test substance. Determination of lymphocyte proliferations was quantified by measuring the incorporation of radiolabelled thymidine in the dividing lymph node cells. The proliferations response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index)
- Criteria used to consider a positive response: Stimulation Index (test substance to control ratio) of greater than 3.0 indicated a positive response.

TREATMENT PREPARATION AND ADMINISTRATION: Following preliminary sighting tests, three groups, each of 4 animals, were treated with 50 µl of the test substance (25 µL per ear) as a solution in dimethyl formamide. A further group was treated with the vehicle alone.

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

Results and discussion

Positive control results:

See field 'Any other information on results incl. tables'

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.35

Test group / Remarks:

5% w/w (based on a group of 4 animals)

Results 2

Parameter:

SI

Value:

1.23

Test group / Remarks:

10% w/w group (based on a group of 4 animals)

Results 3

Parameter:

SI

Value:

1.11

Test group / Remarks:

25% w/w group (based on a group of 4 animals)

Cellular proliferation data / Observations:

No further details available.

Any other information on results incl. tables

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:

GHS criteria not met

Conclusions:

The test substance was considered to be a non-sensitiser under the conditions of the test up to a concentration of 25 % (w/w).