3',4',5'-trifluorobiphenyl-2-amine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2016 - March 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (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

Test material form:

solid: particulate/powder

Details on test material:

Name of test substance: [1,1'-Biphenyl]-2-amine, 3',4',5'-trifluoro-
Batch identification: SK03/186
CAS No.: 915416-45-4
Purity: 99.8 area-% (GC)
Content: 100.0 g/100 g (quant. 1H-NMR)
Identity: Confirmed
99.8 % was used for calculation of 100 mM concentration of DPRA and calculation of final concentrations in the cell-based assays.
Homogeneity: The test substance was homogeneous by visual inspection.
Physical state / color: Solid, beige
Molecular weight: 223.2 g/mol
Log KOW: 3.3

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Postbus 6174, 5960 AD Horst / The Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 21.9 +/- 1.1 g
- Housing: group
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days


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

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

Purity of dimethylformamide: 99%

No. of animals per dose:

5

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: soluble at max. 50%
- Irritation: no excessive skin irritation at 50% test substance concentration
- Systemic toxicity: no systemic toxicity up to 50% test substance concentration

Positive control substance(s):

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

Statistics:

The mean values and standard deviations were calculated in the body weight tables, for the ear weights, the lymph node weights and lymph node cell count, and for the DPM values (group mean DPM ± standard deviation).
All calculations conducted on the DPM values, the ear weights, the lymph node weights and the lymph node cell count were performed with validated program R Script STABW-mitStat.Rnw).
Within the program a statistical analysis conducted on the DPM values, the ear weights, the lymph node weights and the lymph node cell count to assess whether the difference was statistically significant between the test item groups and negative control group. Statistical significance was set at the five per cent level (p < 0.05). Additionally, the Dean-Dixon-Test and Grubb’s Test were used for identification of possible outliers.
However, both biological and statistical significance were considered together.

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

5.5

Test group / Remarks:

10% test substance

Results 2

Key result

Parameter:

SI

Value:

5.8

Test group / Remarks:

25% test substance

Results 3

Key result

Parameter:

SI

Value:

6.9

Test group / Remarks:

50% test substance

Any other information on results incl. tables

In this study the animals neither showed any signs of systemic toxicity nor mortality during the course of the study.

Stimulation Indices (S.I.) of 5.5, 5.8, and 6.9 were determined with the test item at concentrations of 10, 25, and 50% in DMF, respectively. A dose response was observed. An EC3 value could not be calculated, since all valued obtained were above the threshold of 3.

A statistically significant and biologically relevant increase in DPM value and also in lymph node weight and lymph node cellcounts in all dose groups was observed in comparison to the vehicle control group. Furthermore, the cut-off value of 1.55 for a positive response regarding the lymph node cell count index reported for BALB/c mice was exceeded in all dose groups (indices of 2.13, 2.02, and 2.13, respectively).

Applicant's summary and conclusion

Executive summary:

The test item [1,1`-Biphenyl]-2-amine, 3`, 4`, 5`-trifluoro- was found to be a skin sensitiser under the test conditions of this study.