Building on the success of KeratinoSens® – a reference test already leading non-animal testing for skin sensitisation – we have been working with BASF and the Institute for In Vitro Sciences (IIVS), to validate a new approach to predicting skin sensitisation.
Skin sensitisation is an immune reaction that occurs when molecules react with skin protein. The modified skin protein appears foreign to the immune system, which reacts.
Skin sensitisation is a threshold effect however and only occurs above a given exposure. Skin sensitising molecules can still be used in products, we just need to know what dose can be safely used.
This is referred to as the No Expected Sensitization Induction Level (NESIL), a dose not expected to cause induction of skin sensitisation in humans.
Until recently, these levels were determined using a local lymph node assay (LLNA) in mice, a test that involves applying the substance to the ears of mice and then measuring cell proliferation in the local lymph nodes. New regulatory guidelines state however, that this test should only be conducted if in vitro data cannot give sufficient information. We need another solution.
Givaudan researchers have been working towards that using information about the structure of the molecule, reactivity data and KeratinoSens® results to predict an LLNA result as a starting point. They used in vitro and in vivo data on molecules with similar structures to estimate uncertainty of the prediction and applied the approach to three molecules which were subsequently tested in the LLNA to verify the results and 22 molecules with available and sometimes discordant human and LLNA data.