Department Environmental Toxicology
Expanding the fish invitrome for animal-free prediction of chemical toxicity to fish
To date, thousands of fish are being used annually to perform toxicity tests needed to inform environmental risk assessment of chemicals. To reduce the use of animals, alternative (non-animal) toxicity testing methods need to be developed. In the project “Expanding the fish invitrome towards a modular, socio-technical framework for animal-free prediction of chemical toxicity to fish”, we work with permanent cell lines of fish origin, used as proxies to gauge fish organism’s responses to chemical exposure in vivo.
This project is part of the Swiss National Research Program (NRP) 79 “Advancing 3Rs – Animals, research and society”. It is led by Kristin Schirmer (Eawag, ETHZ, EPFL), an expert in fish cell toxicology, and a consortium of further experimental researchers (Ksenia Groh (Eawag) – environmental bioanalytics and proteomics; Colette vom Berg (Eawag) – molecular neurotoxicology) and social scientists (Bernhard Truffer (Eawag, Utrecht University) – technological innovation systems and transitions in urban infrastructures; Jarno Hoekman (Utrecht University) – science and innovation studies).
Earlier, Kristin Schirmer’s group developed an assay based on a cell line derived from rainbow trout gills, RTgill-W1, which was demonstrated to provide reliable predictions of acute toxicity for a large number of chemicals. In 2021, this assay was adopted by the OECD as the first-ever fish cell line-based alternative test for aquatic acute toxicity in fish (OECD Test Guideline 249). Based on this pioneering work, development of a multitude of further assays based on the same principle has been initiated, aiming to cover additional aspects relevant to environmental risk assessment. These include, for example, bioaccumulation, biotransformation, and organ-specific toxicity as well as neurotoxicity and molecular mechanism-based prediction of chronic toxicity outcomes. The latter two aspects are now being addressed in the “fish invitrome” project as well. In particular, the PhD project of Jessica Bertoli, supervised by Colette vom Berg, seeks to establish fish brain cell-based models for neurotoxicity assessment, while the PhD project of Mihai-Ovidiu Degeratu, supervised by Ksenia Groh, seeks to develop a protein marker panel for monitoring the mechanisms of action and progression of toxicity in fish cells.
In addition, since the process from method development to OECD adoption of the initial RTgill-W1 assay has taken more than a decade, this project also seeks to facilitate a faster regulatory uptake of similar fish cell-based assays. Specifically, we collaborate with social scientists and other stakeholders in order to implement a co-design process to develop a modular, computationally-linked framework that integrates several fish cell line-based modules which can be selected and combined in different ways depending on the chemical assessment purpose.
Further information on the individual projects comprising the NRP79-funded project consortium “expanding the fish invitrome for toxicity prediction” can be found at the respective links provided above.
