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

Endpoint summary

Description of key information

in vitro sensitization testing battery: inconclusive

LLNA: sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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

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)

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

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.

Key result

Parameter:

SI

Value:

5.5

Test group / Remarks:

10% test substance

Key result

Parameter:

SI

Value:

5.8

Test group / Remarks:

25% test substance

Key result

Parameter:

SI

Value:

6.9

Test group / Remarks:

50% test substance

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).

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

An in vitro sensitization testing battery was conducted, however the overall result of the IATA was "inconclusive". In order to clarify the sensitizing potential of the test substance, an LLNA was conducted, which gave stimulation indices >3 for all concentrations tested.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data available and according to Regulation (EC) 1272/2008 (CLP), the substance is a skin sensitizer Cat. 1. The data do not allow for potency deduction since no EC3 value could be determined in the LLNA. Therefore, classification as H317 (may cause an allergic skin reaction) is warranted.