4-chloro-α,α,α-trifluorotoluene

Endpoint summary

Description of key information

Skin sensitising

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The aim of this study was to evaluate the skin sensitization potential of 4-chloro-a,a,a-trifluorotoluene (PCBTF) following dermal exposure in the Local Lymph Node Assay, according to the OECD guideline 429. The test item was a liquid hence applicability of the 100 % concentration (the undiluted test item) was evaluated in order to test the highest test concentration possible. Further test concentrations were achieved by formulation of the test item inN,N-Dimethylformamide (DMF). Both the undiluted test item and the formulations were adequately applicable on the ears of animals. Based on results of the preliminary irritation/toxicity test 4-chloro-a,a,a-trifluorotoluene (PCBTF) was examined in the LLNA at concentrations of 100 % as the undiluted test item and as 75 %, 50 % or 25 % (w/v) formulations in DMF according to the relevant guidelines.

28 female CBA/Ca mice were allocated to 7 groups of four animals each:- four groups received4-chloro-a,a,a-trifluorotoluene (PCBTF)at four different concentrations of 100 %, 75 %, 50 % and 25 % (w/v), - the positive control group receiveda-Hexylcinnamaldehyde (HCA) at concentration of 25 % (w/v), - one control group (used as negative control for the groups treated with the test item) received the vehicle of the test item (DMF) only, - one control group (used as negative control for the group treated with the positive control substance) received the vehicle of the positive control (AOO) only. Each substance was applied on the external surface of each ear of the animals for three consecutive days (Day 1, 2 and 3). There was no treatment on Days 4, 5 and 6. On Day 6 animals were intravenously injected via the tail vein with tritiated methyl thymidine (³HTdR), than sacrificed approximately 5 hours after the injection. Auricular lymph nodes were removed and processed. The cell proliferation in the local lymph nodes was measured by incorporation of³HTdR and the obtained values were used to calculate stimulation indices (SI). The positive control item (25 % HCA in AOO) induced the appropriate (SI ³ 3) stimulation over the control (SI value was 11.2), thus confirming the validity of the assay. No mortality was observed during the study. No significant, treatment related effect on body weights or any other signs of systemic toxicity were observed in any treatment group during the test. No signs of significant irritation or any other local effect were observed at the treatment site (ears) in any treatment group. Visually largerlymph nodes than the relevant controls were observed in the positive control group only. Visual appearance of the lymph nodes was normal in the negative control groups (both DMF and AOO) and in the test item treated groups. In spite of normal visual appearance of the lymph nodes significantly increased lymphoproliferation (indicated by an SI ³ 3) compared to the relevant control (DMF) was noted for 4-chloro-a,a,a-trifluorotoluene (PCBTF)at concentrations of 100 %, 75 % and 50 %. No significantly increased lymphoproliferation was observed at test item concentration of 25 %. The stimulation index values were 7.3, 6.9, 8.1 and 1.1 at concentrations of 100 %, 75 %, 50 % and 25 %, respectively. Dose-related response was observed, although its linearity was not statistically significant(p = 0.30, r = 0.70, evaluated by linear regression using SI values). 

Since the test was valid and no sign of systemic toxicity or irritation was observed, the proliferation values obtained are considered to reflect the real potential of the test item to cause/not cause lymphoproliferation in the Local Lymph Node Assay. Although

linearity of the observed dose-response proved not to be statistically significant, the increased lymphoproliferation observed at three test concentrations (100 %, 75 % and 50 %) is considered evidence that4-chloro-a,a,a-trifluorotoluene (PCBTF) has sensitization potentialaccording to evaluation criteria of therelevant guidelines. 

EC₃calculation was conducted by linear interpolation using data points lying immediately above and below the SI value of 3 on the LLNA dose-response curve. The calculated EC₃value of 4-chloro-a,a,a-trifluorotoluene (PCBTF) based on the dose-response was 31.8 % in this LLNA. Using the EC₃value.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the EC3 value calculated using the dose-response curve (31.8 %), PCBTF was classified as sensitising Sub-category 1B according to the CLP Regulation (EC) No 1272/2008.