Inlivetox
Structure de mise en forme 2 colonnes

Increasing concerns about the safety of new active chemical ingredients used in pharmaceuticals, cosmetics and the food industry have been further highlighted by the emergence of materials with dramatic new properties based on nanoparticles (NPs). NPs are particles with at least one dimension on the nano-scale of 100nm or less. Ethical concerns about the use of animals to test the safety or efficacy of new compounds are growing. In vitro testing offers a potential solution to the challenge of how to ensure that as NPs are developed and used, any unintended consequences of exposure to humans are minimised. The InLiveTox project, funded by EU over the past three years, has significantly advanced the capability of in vitro testing in particular of NPs.

The InLiveTox project focused on the impact of NP exposure via ingestion, on the vascular endothelium, liver and gastrointestinal tract (GI). Exposure via ingestion is particularly relevant due to the inclusion of NPs in food, food packaging and in oral medicines.

The key questions to be addressed were:

  • How do these tissues individually respond to NPs?

  • How do the interactions between the different tissues modulate their responses?

  • How does inflammation affect the toxicity of NPs and their ability cross the intestinal barrier?

Leaflet

The partners in InLiveTox were an interdisciplinary consortium including European leaders in nanotoxicology, pharmacy and engineering. The consortium developed a novel modular fluidics-based in vitro test system and demonstrated its use to model the response of selected tissues to the ingestion of NPs. The results from the in vitro system were validated by an in vivo study of NP biokinetics and toxicity by ingestion in rats carried out in parallel.
Comparison of the data obtained in vivo on exposure by injection and ingestion with data obtained from standard (static, single cell type) assays and the InLiveTox system showed a remarkable pattern of differences and similarities particularly when studying inflammation. There are clear differences in the physiological relevance of the different approaches.

The InLiveTox system developed in this project has wider application than just the testing of response to NPs. It can be used as a testing and research tool in toxicology and pharmacology for any new chemical entity. Throughout the project there has been extensive dialogue with members of an Industrial Advisory Group whose from the pharmaceutical, cosmetics, food and household products manufacturing industries.

Technical outputs from the project include tested prototypes of a cell culture system that will be commercialized by partners from the consortium. Cell culture protocols and assay protocols for toxicity studies and screening of ingested NP toxicity will support the adoption of this new system by industry and the academic research community.