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BodyTox 2.0: Simulation of neurotoxin toxicity via skin uptake route using a body-on-a-chip technique.

|   Call 2021

The FORTE collaborative project BodyTox is dedicated to a body-on-a-chip method for more effective risk assessment of chemical warfare agents based on their toxicity, exposure duration and penetration properties of nerve agents. To implement the project, 3D organoid tissue models of a wide variety of human organs are being developed with microfluidics and biosensing technologies for automated analysis of potential warfare and hazardous agents via the skin uptake route.

Despite comprehensive international agreements and a verification regime to control the production and use of chemical warfare agents, including the group of nerve agents (GA, GB, GD, GF and VX), they still pose a threat potential that should not be underestimated due to the probability of occurrence of terrorist scenarios. This assumption is justified by the proliferation of materials and relatively simple chemical technologies for their production. Uniform long-term and short-term studies on the uptake and toxicity of warfare agents are largely lacking, which makes a reliable risk assessment based on the existing heterogeneous data landscape extremely difficult. Data as well as compilations for risk assessment are available but outdated based on studies from the 1950s with the attempt to set exposure limits mainly for dermal and air exposure. For many warfare agents there is no or inaccurate information on skin exposure. Limits are often given in grams/person being is very inaccurate and variable. However, to assess the risks following the use of nerve agents, it is necessary to have reliable data on the toxicological properties. In the accessible literature, the data on this are often contradictory or not or only partially verifiable according to scientific criteria. In addition, only very few data are based on human cell tests or on medical examinations after accidents. An important parameter for nerve agent toxicity is cholinesterase activity (ChE), although again the data situation is limited and prone to high variability. At a ChE activity decrease of 50-80%, first symptoms may appear. These data are based on a single exposure only and ignore cumulative effects of lower doses occurring over a longer period (e.g., contamination of equipment and utensils). The BodyTox 2.0 consortium will develop the first 'fit-for-purpose' body-on-a-chip system for neurotoxin studies, enabling individualized and non-invasive organ-specific readout by integrating gas-tight lab-on-a-chip strategies and non-invasive microsensors. By combining the interdisciplinary expertise in the consortium, the body-on-a-chip technology to be developed will stand out significantly from the stand-of-the-art systems for toxicological evaluation.

[Translate to English:] Bundesministerium für Finanzen
[Translate to English:] Österreichische Forschungsförderungsgesellschaft - FFG
[Translate to English:] Bundesministerium für Landesverteidigung