Local Tolerance Studies
For many new formulations and compounds it is not only important to investigate toxicity following systemic exposure but also to investigate whether the compound gives rise to local toxicity. This can be done in local tolerance studies.
At Scantox, we have experience with topical application of oral patches and thin films placed either on the buccal surface or sublingual. We also have experience with ocularly administered compounds and investigating the local tolerance following parenteral administration such as intravenous, intramuscular, subcutaneous, or intraperitoneal.
Topical application or parenteral administration
In cases where a compound is already on the market and only the formulation is altered, it is sufficient to perform a local tolerance study, possibly in combination with a kinetic study. For new compounds, general toxicity studies are required.
Learn more about general toxicity
Kinetic study and profile
Kinetic studies evaluate the local tolerance at the application site. The systemic exposure will be assessed by investigating the kinetic profile of the compound. Based on this, it will be determined if the new formulation gives rise to a similar systemic exposure as the former formulation and if potential local reactions are reduced or absent.
Local tolerance studies not only apply for compounds administered by dermal application but also to a variety of other topical dosing routes.
Hamster and rabbit in tolerance testing
Other species used for local tolerance testing include hamsters and rabbits. Hamsters are often preferred when testing for local tolerance at the mucous membrane (cheek pouch testing). For other products, the size of the hamster is less ideal, and dogs or minipigs are better choices for assessing local tolerance orally. Rabbits are used when testing on very sensitive skin is relevant and are often used when testing local tolerance following “unintended route of dosing”.
Minipigs in local tolerance studies
For several administration routes, the minipig has proven to be an excellent model to study local tolerance. With decades of experience, Scantox has developed unrivalled expertise in administering dermal formulations to minipigs, ranging from very small to large volumes, ensuring the model is clinically relevant and that there will be no cross-contamination. We specialize in performing local tolerance studies to ensure long daily exposure as well as multiple daily dosing if necessary.
Lymph node Assay (LLNA)
For skin sensitization tests, the OECD 429 has been in place for a number of years: Skin sensitization test using the Local Lymph node Assay (LLNA).