Hepatic 3D spheroids: the next generation of testing in toxicology (SPHERTOX)

Alternatives to animal testing have long been sought by implementing the 3Rs (refinement, reduction and replacement), to more efficiently assess the safety of chemicals, endorse ethical considerations and reduce costs of experimental studies. Regulatory legislations have in recent years required more chemicals to be assessed for hazard, increasing the need for testing of toxicity and chemical’s potential to accumulate in organisms (bioconcentration (BC)). Thus, efforts to implement (non-animal) alternative testing, with key focus on fish has intensified. Recent advances within cell-based toxicity and BC assessment for fish has resulted in standardized tests with short exposure times. There is currently no satisfying cell model accommodating long-term toxicity testing and/or BC assessment of slowly metabolized chemicals. The SPHERTOX project will therefore investigate the suitability of using Rainbow trout (RT)liver cells organized in a liver mimicking structure (spheroids). This project seeks to provide theoretical and experimental data to develop and evaluate the next-generation ecotoxicological methodologies using fish for end-users within the academic, industry and regulatory community. The proposed work will be performed through a multi-disciplinary approach, developing and applying novel and established computational and experimental methods to compare towards existing non-animal and animal testing data. The proposed work is expected to have a significant impact on how data from cell-based methods is utilized both directly and in computational models to reduce animal testing. SPHERTOX will establish a communication platform towards multiple stakeholders to ensure dissemination of the outputs of the project. The project will be led by the Norwegian Institute for Water Research, with collaborators from leading Universities and companies from United States of America, United Kingdom and Switzerland.

Alternatives to animal testing have long been sought by implementing the 3Rs (refinement, reduction and replacement), to more efficiently assess the safety of chemicals, endorse ethical considerations and reduce costs of experimental studies. Regulatory legislations have in recent years required more chemicals to be assessed for hazard, increasing the need for toxicity and bioconcentration (BC) testing. Thus, efforts to implement (non-animal) alternative bioassays, with key focus on fish, has intensified. Recent advances within in vitro fish acute toxicity and BC assessment has resulted in standardized tests with short exposure times. There is currently no satisfying in vitro model accommodating chronic toxicity testing and/or BC assessment of chemicals with low biotransformation rate. The SPHERTOX project will therefore investigate the suitability of hepatic 3D spheroids of Rainbow trout (RT) to accommodate such, both alone and in co-culture with RT gill cells. This proposal seeks to provide both basic and applied knowledge by generating theoretical and experimental data to develop and evaluate the next-generation ecotoxicological methodologies for fish for end-users within the academic, industry and regulatory community. The proposed work will be performed through a multi-disciplinary approach, developing and applying novel and established computational (in silico) and experimental methods to compare towards existing in vitro and in vivo testing data. The proposed work is expected to have a significant impact on how in vitro data is utilized both directly and in silico to reduce animal testing. SPHERTOX will establish a communication platform towards multiple stakeholders to ensure dissemination of the outputs of the project. The project will be led by the Norwegian Institute for Water Research, with the objective to endorse early career researchers and enroll one PhD student to perform cutting-edge science, with the support of senior researchers.