2-Dibenzofuranyl-1-4,6-diphenyl-[1,3,5]-triazine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 05 - Apr 07, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Biphenyl-4-yl- biphenyl-2-yl-amin

Cas Number:

1372775-52-4

Molecular formula:

C24 H19 N

IUPAC Name:

Biphenyl-4-yl- biphenyl-2-yl-amin

Test material form:

solid

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS B.V., Inc Postbus 6174 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 12 weeks
- Weight : 18.0 +/- 1.1 g
- Housing: grouped per dose
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 45-65%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: day 1 To: day 6

Study design: in vivo (LLNA)

Vehicle:

methyl ethyl ketone

Concentration:

2.5, 5, and 10 (w/w)

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: 10% in Propylene glycol

Range Finding Exp. 1
- Concentration used: 5, 10 %
- Irritation:no irritation observed

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: OECD 429
- Concentration: 2.5, 5, and 10%
- Criteria used to consider a positive response: Stimulation index > 3

Positive control substance(s):

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

Statistics:

Standard statistical methods have been applied for data processing.

Results and discussion

Positive control results:

Conc. SI
0%: 1.0
5% 1.68
10% 1.78
25% 8.19

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

Test Group: 2.5% in PG

Results 2

Key result

Parameter:

SI

Value:

1.1

Test group / Remarks:

Test Group: 5% in PG

Results 3

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

Test Group: 10% in PG

Cellular proliferation data / Observations:

The EC3 value could not be calculated, since all group S.I.´s are below the threshold value of 3.

CLINICAL OBSERVATIONS: No symptoms of local skin irritation at the ears of the animals and no signs of systemic toxicity were observed during the study period.

BODY WEIGHTS: The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Any other information on results incl. tables

Calculation of Stimulation Indices per Dose Group

Test item concentration	Group Calculation
	Mean DPM per animal (2 lymph nodes)	SD	S.I.
PG (Vehicle Control)	1037.7	177.9	1.0
2.5 % Test Item in PG	1044.7	324.1	1.0
5 % Test Item in PG	1147.9	273.0	1.1
10 % Test Item in PG	1045.9	417.2	1.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was not a skin sensitiser under the test conditions of this study.

Executive summary:

Objective

In the study the test item formulated in propylene glycol (PG) was assessed for its possible skin sensitising potential.

Study Design

For this purpose a local lymph node assay was performed using test item concentrations of 2.5, 5, and 10 (w/w). The highest concentration tested was the highest concentration that could technically be achieved. A control group of five mice was treated with the vehicle (methyl ethyl ketone) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per animal. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a β-scintillation counter.

Results

All treated animals survived the scheduled study period and no signs of systemic toxicity or local skin irritation were observed.

In this study Stimulation Indices of 1.0, 1.1, and 1.0 were determined with the test item at concentrations of 2.5, 5, and 10% in PG. The EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3.

Conclusion

The test item was not a skin sensitiser under the test conditions of this study.