1,1,1,2,3,3-hexafluoro-2-(heptafluoropropoxy)-3-[(trifluorovinyl)oxy]propane

Endpoint summary

Description of key information

An in chemico skin sensitization study was conducted on PPVE-2. The result of the study was:

 

The test article was determined to have no or minimal reactivity (1.8% mean depletion) in a Direct Peptide Reactivity Assay (DPRA) (OECD 442C).

Key value for chemical safety assessment

Respiratory sensitisation

Endpoint conclusion

Additional information:

The skin sensitization potential of the test article was evaluated in the Direct Peptide Reactivity Assay (DPRA). The assay was conducted according to OECD guideline 442C. The study was performed in compliance with OECD GLP (1997). The test article was prepared at concentration of 100 mM in isopropyl alcohol and 50 uL of the test material solution was incubated for 24 hours at 25 degrees C with 750 uL of the stock cysteine peptide solution. Similarly, 250 uL of the test article solution was incubated for 24 hours at 25 degrees C with 750 uL of lysine peptide stock solution. Appropriate positive (100 mM cinnamic aldehyde) and negative (100 mM Ammonium Acetate Buffer) controls were run in parallel.  Following incubation, relative peptide concentrations were measured by high performance liquid chromotagraphy (HPLC) with gradient elution and ultraviolet detection at 220 nm. Cysteine and lysine peptide percent depletion values were calculated compared to negative control values and used in a prediction model which allowed the assigning of the test chemical to one of four reactivity classes used to support the discrimination between sensitizers and non-sensitizers. The mean percent cysteine depletion for the test substance assay samples was 1.88 ± 0.57% (N = 3; CV = 30.3%).  The mean percent lysine depletion for the test substance assay samples was 0.00 ± 0.00% (N = 3).  Precipitate was not present in the cysteine test substance assay samples upon initial preparation of both test substance solutions (i.e. 0 hours) and following approximately 24 hours of incubation. Precipitate was present in the lysine test substance assay samples upon initial preparation of both test substance solutions (i.e. 0 hours) and following approximately 24 hours of incubation. Based on the results of the study, the test article is considered to have no or minimal cysteine and lysine reactivity and a negative DPRA prediction.

 

Read-across and computational profiling were also conducted to create a weight of evidence to support a classification. The results of these efforts were:

 

Read-across: Both the target (PPVE-2) and the source (PPVE-1) structures contain the same functional groups (fluorinated vinyloxy) with the target structure containing an additional heptafluoropropanol group. Both the source and target chemical have log Kow values greater than 3.9 (4.0 and 6.2, respectively) and molecular weights greater than 185 (266 and 432, respectively) indicating that they would be expected to have poor dermal penetration irrespective of reactivity profile and, as a result, would not be expected to have dermal sensitization potential (Jaworska et al., 2011). As a result, the negative LLNA results from the source chemical are appropriate to read-across to the target chemical. Reference: Jaworska, J. (2011). Integrating non-animal test information into an adaptive testing strategy – skin sensitization proof of concept case. Altex, 28(3), 211-225. doi:10.14573/altex.2011.3.211

 

Computational Profiling: When evaluated with the skin sensitization profiling schemes available in OECD QSAR Toolbox v. 4.2, neither the source or target chemical trigger structural alerts for sensitization.

Justification for classification or non-classification

Based on the weight of evidence, the test article is not a skin sensitizer.