Toxicology-testing platform integrating immunocompetent in vitro/ex vivo modules with real-time sensing and machine learning based in silico models for life cycle assessment and SSbD

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Safe and Sustainable by Design approach requires an entire life cycle monitoring of toxicity of chemicals. However, current testing systems cannot mimic the exposure conditions related to each step and are not compatible with downstream in silico analyses. New sets of instrumentation that enables modular testing capacities with integrated data bridging and progressive in silico model development systems are needed. TOXBOX will provide a device based on a prototype developed in a H2020 project, PANBioRA, with a flexible microfluidic and instrument architecture to provide a plug and play testing platform to ease accessibility and interlaboratory validation. The system will incorporate the following tests, with modifications for each step of life cycle: automated cytotoxicity and genotoxicity tests, connected barrier/metabolic tissue couples with cytokine and real-time electro-chemical read-outs, flow cycle modules with environment mimicking conditions, a testing module based on zebrafish embryo with mechanical stimuli. The system will be validated using metallic 2D structures and nanoparticles, biocides, and known endocrine disruptors. Custom made functional polypeptides (novel biocides) will be used to cover the design phase. Progressive in silico models for long term effects will be iteratively developed and used to predict each new group to be tested until good predictability is achieved with new chemical formulations (comprehensive risk assessment). A data management platform that enables interfacing with the available databases will be developed. After interlaboratory validation of the device by 4 partners, a standardization folder will be prepared, to make the device available for testing with accessibility at all stages of material life cycle assessment to different stakeholders. TOXBOX aspires to bring forth an instrument that will provide reliable toxicity data in relevant conditions for each chemical and enable reliable in silico model development.