4-bromo-2,2-diphenylbutanenitrile

Endpoint summary

Description of key information

Skin sensitization

In a Local Lymph Node Assay (LLNA) in mice (CBA/Ca strain) according to OECD Guideline 429, the substance is observed to be non-sensitising to the skin (Sanders, 2004). An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (intiated before October 11th, 2016) is available.

 

Respiratory sensitization

No study is available to assess the potential for respiratory sensitisation.

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:

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

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

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)

Specific details on test material used for the study:

No further details available

Species:

mouse

Strain:

CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

No data

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

Positive control results:

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

Parameter:

SI

Value:

1.35

Test group / Remarks:

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

Parameter:

SI

Value:

1.23

Test group / Remarks:

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

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.

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:

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).

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Sanders (2004) investigated the skin sensitization potential of T000625 following topical application to the dorsal surface of the ear of CBA/Ca mice. Primary lymphocyte proliferation was assessed during the sensitizing (induction) phase of the response. Following a preliminary sighting test at which there were no signs of systemic toxicity at a concentration of 50%, 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 10%, 25% and 50% w/w in  in dimethyl
formamide. A further group of four animals was treated with dimethyl formide alone. The following stimulation index (SI) values were observed: at 5% concentration: 1.35 (negative result), at 10% concentration: 1.23 (negative result), and at 25%: 1.11 (negative result).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitization

The test item was considered to be non-sensitizing under the conditions of the test, up to a concentration of 25% (w/w). The substance does not have to be classified as a skin sensitizer, according to the criteria laid down in the CLP Regulation No 1272/2008.

 

Respiratory sensitization

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