Wednesday, 11 October 2023 11:26

Skin sensitization: new database supports animal-free approaches Featured

A team of researchers from the German Federal Institute for Risk Assessment (BfR) and the U.S. NICEATM (National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods), together with other colleagues from the U.S., has published a comprehensive database on allergic skin reactions to chemical substances. Information from the database is intended to support the evaluation of results from non-animal methods.

The database contains countless human data; it is the most comprehensive to date. This is necessary because there are already animal-free approaches whose application range is limited.

A home sensitization process is characterized by initial contact "priming" the immune system to the contact substance, so that a renewed contact quickly leads to an allergic reaction.

Classically, two animal tests are possible: the skin sensitization test on the guinea pig ("Buehler test",TG 406) and the Local Lymph Node Assay (LLNA) on the mouse in three different versions (TG 429 with radioactive markers, 442A and TG 442B non-radioactive). While the Buehler test is considered by users to be of animal welfare concern, the LLNA has limitations: it only looks at the initiation of sensitization and does not actually detect it at the end. The tests have not yet been eliminated despite the existence of animal-free procedures.

Several animal-free individual developments already exist, but all have limitations. So-called in chemico and in vitro test methods (OECD TG 442C, 442D, 442E) characterize the first three key events for skin sensitization, but none of these animal-free methods is considered in itself a sufficient substitute for animal data.

To provide equivalent or better predictions than animal testing, there is the so-called defined approach. It is based on results from several sources of information describing in vitro and in silico the binding of electrophilic substances to nucleophilic skin proteins, the reactions in keratinocytes as well as changes in gene expression, surface markers on dendritic cells, inflammatory messengers or the proliferation of T cells.  However, the approach also has limitations: For example, certain types of chemicals such as metals, inorganic compounds, UVCBs, and mixtures may be excluded from the scope. Also, some predictions may be inconclusive. Therefore, the human data base is always being updated. Therefore, the new comprehensive database is very welcome. It has already been used to support international acceptance of an animal-free strategy for identifying allergenic substances.

Information from the database will be made available to developers of animal-free methods in this field worldwide.

More information:
https://www.bfr.bund.de/cm/343/hautallergien-neue-datenbank-hilft-tierversuchsfreie-testmethoden-zu-entwickeln.pdf
https://factor.niehs.nih.gov/2023/10/science-highlights/chemical-safety-testing-database
https://www.oecd-ilibrary.org/environment/guideline-no-497-defined-approaches-on-skin-sensitisation_b92879a4-en