E. Schmidt, V. Zuckerstätter, H. Gehrke | Eurofins BioPharma Product Testing Munich GmbH
A skin sensitiser refers to a substance that will lead to an allergic response following skin contact as defined by the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS). The potential to induce skin sensitisation is an important consideration included in procedures for the safe handling, packaging and transports of chemicals.
The assessment of skin sensitisation typically involves the use of laboratory animals. Classical methods comprise the Magnusson Kligman Guinea Pig Maximisation Test, the Buehler Test (TG 406) as well as the local lymph node assay, in its radioactive and non-radioactive form (TG 429, TG 442A/B). In order to replace in vivo experiments validation studies on alternative, mechanistically based in chemico and in vitro test methods on skin sensitisation were conducted under the auspices of ECVAM and have been considered scientifically valid for the evaluation of the skin sensitisation hazard of chemicals.
Genomic Allergen Rapid Detection (GARDTM) is an in vitro assay designed to predict the ability of chemical substances to induce skin sensitisation based on the analysis of the relative expression levels of a biomarker signature of 196 genes using a human myeloid leukaemia cell line called SenzaCells. The GARDTM assay is based on chemical stimulation of the SenzaCells, acting as an in vitro model of human Dendritic Cells (DCs). The readout of the assay is a transcriptional quantification of the genomic predictors, collectively termed the GARDTM Prediction Signature (GPS), using Nanostring nCounter technology.
The DPRA, KeratinoSensTM and h-CLAT are well known sensitization assays which address three different key events of the AOP. The GARDTM skin assay is a new procedure that analyses the sensitization potential based on almost 200 human genes. If a substance is a skin sensitiser with the GARDTM skin assay you have the benefit of measuring the potency on top with a different code set to make a 1A or 1B classification.
The GARDTM skin assay is especially for products that have a high log Pow (h-CLAT > 3.5, KeratinoSensTM > 7) because in those cases the classical sensitization tests are inconclusive if negative and there is no option for a replacing test method. Therefore, the GARDTM skin assay is not only an excellent alternative of the sensitization methods for these cases but it can furthermore predict the potency of a skin sensitiser, a unique feature, which makes it a testing method needed in the future.
Poster publication at Eurotox, Helsinki, Sep 9, 2019.