Toward Precision Toxicology: New Approach Methodologies for Chemical Safety

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Deliverables

Stakeholder-driven priorities document published by SAG

We will take advantage of our first kickoff meeting to elaborate the report to highlight SAG roles in developing longterm project applications and bring their own sectors and organisations priorities in line with the overall PrecisionTox goal and Project objectives

Shortlist of exploitation options for industry usage of NAM biomarkers

This deliverable maps those areas of EU law in which forms of chemical risk assessment are mandated or encouraged. Producing this overview of the relevant regulatory settings enables an analysis of the functionality of NAM biomarkers and their capacity to deliver on regulatory imperatives. We would envision a web based tool that would assist both researchers and regulatory agencies to locate appropriate settings for NAM biomarkers.

Protocols for routine and higher-throughput processing of experimental samples for multi-omics analysis

Written Standard Operating Protocols will be written that are version controlled and that provide a stepbystep set of instructions on how to conduct automated and highthroughput extractions for RNA and metabolite analysis for each of the NSOs and human cell lines A detailed description on how to incorporate a beadbased tissue and cell homogeniser and stateoftheart liquid handling robotics will be included

First loaded database and associated schema

First version of the central database for the PrecisionTox project will be created for the purposes of managing all of the data produced by or used by the consortium This database will allow fast and relevant queries by defining links between chemicals genesproteins phenotypes and all of the associated information that can be obtained from existing external sources In addition to simple textbased queries it will offer sequence eg BLAST and chemoinformatics eg Open Babel RDKit CDK searches

Report on socio-technical barriers to the take up of NAMs

This report addresses factors which may inhibit the take-up on NAMs. Such factors are not merely technical but involve a range of social, economic and political factors that may create path dependency on existing methods and even resistance to transition. The socio-technical analysis explores how co-production of NAMs through multidimensional engagement around industrial imperatives, market behaviours, chemicals policy, civil society perspectives and technological innovation may help embed NAMs into the fabric of chemical risk assessment.

Project website

We will first explore alternatives for web frameworks, consult graphic designers and launch the website with content by M3. The website will include a presentation of the project objectives and partners, a repository for open access peer reviewed publication (subject to dissemination permissions from the Project), newsletters, links to partners websites, regular updates regarding the project developments and activities (events, webinars), and will embed videos, podcasts, articles and press releases.

Data Management Plan

Written Data Management Plan DMP that incorporates the outputs of the WPs following H2020 project guidelines defining a strategy that ensures findability accessibility interoperability and reusability of all digital asset ensuring FAIRness in all phases of the data life cycle ie data generation curation storage processing handling metadata and dissemination of and access to the project data The report will document the data format specifications terminologies and data repositories vetted by the community and relevant to the project A first initial plan will be formulated at month 12 and the final version of the PrecisionTox Data Management Plan will be made available at month 36

Data submission to Data Commons (WP5) with response profiles for 50 chemicals

All phenotypic measurement data (except for the omics data that is generated and described in WP3) – for the first 50 test chemicals – will be reported to the Data Commons. This will include cytotoxicity data, measurements of embryo toxicity and teratology, measurements of endocrine disruption endpoints, cardiotoxicity and photomotor and other motor behaviours.

Publications

A web-based histology atlas for the freshwater crustaceanDaphnia magna

Author(s): Mee S. Ngu; Daniel J. Vanselow; Carolyn R. Zaino; Debra A. Shearer; Chadwick Harris; Maksim A. Yakovlev; Spencer R. Katz; Alex Y. Lin; Jean E. Copper; Dula Parkinson; Margaret J. Beaton; John K. Colbourne; Keith C. Cheng; Khai C. Ang
Published in: 2022
Publisher: bioRxiv
DOI: 10.1101/2022.03.09.483544

Community-driven governance of FAIRness assessment: an open issue, an open discussion

Author(s): Wilkinson, Mark D.; Sansone, Susanna-Assunta; Méndez, Eva; David, Romain; Dennis, Richard; Hecker, David; Kleemola, Mari; Lacagnina, Carlo; Nikiforova, Anastasija; Castro, Leyla Jael
Published in: Open Research Europe, 2023, ISSN 2732-5121
Publisher: F1000 Research Limited on behalf of the European Commission
DOI: 10.12688/openreseurope.15364.1

The herbicide acetochlor causes lipid peroxidation by inhibition of glutathione peroxidase 4

Author(s): Fahmi Mesmar, Maram Muhsen, Jason P. Tourigny, Jason M. Tennessen, Maria Bondesson
Published in: 2023
Publisher: bioRxiv
DOI: 10.1101/2023.04.14.536563

Arsenic Toxicity in the Drosophila Brain at Single Cell Resolution

Author(s): Anurag Chaturvedi, Vijay Shankar, Bibhu Simkhada, Rachel A. Lyman, Patrick Freymuth, Elisabeth Howansky, Katelynne M. Collins, Trudy F. C. Mackay, Robert R. H. Anholt
Published in: Frontiers in Toxicology, Issue 7, 2026, ISSN 2673-3080
Publisher: Frontiers Media SA.
DOI: 10.1101/2025.04.09.647950

Zebrafish regulatory genomic resources for disease modelling and regeneration

Author(s): Ada Jimenez Gonzalez; Damir Baranasic; Ferenc Müller
Published in: Disease Models & Mechanisms, Issue Volume 16, Issue 8, 2023, ISSN 1754-8411
Publisher: Company of Biologists
DOI: 10.1242/dmm.050280

Drosophila Toxicogenomics: genetic variation and sexual dimorphism in susceptibility to 4-Methylimidazole

Author(s): Katelynne M. Collins, Elisabeth Howansky, Sarah C. Macon-Foley, Maria E. Adonay, Vijay Shankar, Richard F. Lyman, Nestor Octavio Nazario-Yepiz, Jordyn K. Brooks, Rachel A. Lyman, Trudy F. C. Mackay, Robert R. H. Anholt
Published in: Human Genomics, Issue 18, 2024, ISSN 1479-7364
Publisher: Springer Nature
DOI: 10.1186/s40246-024-00689-3

Interactions between phenanthrene exposure and historical chemical stress: Implications for fitness and ecological resilience of the sentinel species Daphnia magna

Author(s): Florian Gigl, Muhammad Abdullahi, Marianne Barnard, Henner Hollert, Luisa Orsini
Published in: Science of The Total Environment, Issue 949, 2025, Page(s) 174963, ISSN 0048-9697
Publisher: Elsevier BV
DOI: 10.1016/j.scitotenv.2024.174963

Reactivity of Acrylamides Causes Cytotoxicity and Activates Oxidative Stress Response

Author(s): Julia Huchthausen, Beate I. Escher*, Nico Grasse, Maria König, Stephan Beil, and Luise Henneberger
Published in: Chemical Research in Toxicology, Issue Volume 36, 2023, Page(s) 1374-1385, ISSN 0893-228X
Publisher: American Chemical Society
DOI: 10.1021/acs.chemrestox.3c00115

"Preprint: ""Be Sustainable Recommendations"" for FAIR Resources in Life Sciences research: EOSC-Life's Lessons"

Author(s): David, Romain; Rybina, Arina; Burel, Jean-Marie; Heriche, Jean-Karim; Audergon, Pauline; Boiten, Jan-Willem; Coppens, Frederik; Crockett, Sara; Exter Katrina; Fahrener, Sven; Fratelli, Maddalena; Goble, Carole; Gormanns, Philipp; Grantner, Tobias; Gruning, Bjorn; Gurwitz, Kim Tamara; Hancock, John; Harmse, Henriette; Holub, Petr; Juty, Nick; Karnbach, Geoffrey; Karoune, Emma; Keppler, Antje; Kleme
Published in: EMBO journal, 2023, ISSN 1460-2075
Publisher: European Molecular Biology Organization
DOI: 10.15252/embj.2023115008

Effects of Chemicals in Reporter Gene Bioassays with Different Metabolic Activities Compared to Baseline Toxicity

Author(s): Julia Huchthausen, Jenny Braasch, Beate I. Escher, Maria König, Luise Henneberger
Published in: Chemical Research in Toxicology, Issue 37, 2024, Page(s) 744-756, ISSN 0893-228X
Publisher: American Chemical Society
DOI: 10.1021/acs.chemrestox.4c00017

Bioactivity Profiling of Chemical Mixtures for Hazard Characterization

Author(s): Xiaojing Li, Jiarui Zhou, Yaohui Bai, Meng Qiao, Wei Xiong, Tobias Schulze, Martin Krauss, Timothy D. Williams, Ben Brown, Luisa Orsini, Liang-Hong Guo, John K. Colbourne
Published in: Environmental Science & Technology, Issue 59, 2025, Page(s) 291-301, ISSN 0013-936X
Publisher: American Chemical Society
DOI: 10.1021/acs.est.4c11095

Alternative Vertebrate and Invertebrate Model Organisms Show Similar Sensitivity as Rodents to a Diverse Set of Chemicals

Author(s): Gaëlle Hayot, Gavin R. Lloyd, Gaurav D. Diwan, Nathan Keith, Shannon R. Smoot, Christina A. Cramer von Clausbruch, Thomas C. Kaufman, Marianne Barnard, Andrew J. Tindall, Stephen P. Glaholt, Riccardo Massei, Rubén Martínez, Uwe Strähle, Luisa Orsini, Robert B. Russell, Jason M. Tennessen, Stefan Scholz, Joseph R. Shaw, Jonathan H. Freedman, John K. Colbourne, Carsten Weiss, Thomas Dickmeis
Published in: Environmental Science & Technology, Issue 59, 2025, Page(s) 25634-25648, ISSN 0013-936X
Publisher: American Chemical Society
DOI: 10.1021/acs.est.5c10177

Assessment of Chemical Toxicity in Adult Drosophila Melanogaster

Author(s): Jessica M. Holsopple; Shannon R. Smoot; Ellen M. Popodi; John K. Colbourne; Joseph R. Shaw; Brian Oliver; Thomas C. Kaufman; Jason M. Tennessen
Published in: JoVE, Issue 193, 2023, ISSN 1940-087X
Publisher: MYJoVE Corporation
DOI: 10.3791/65029

ELIXIR and Toxicology: a community in development

Author(s): Marvin Martens; Rob Stierum; Emma L. Schymanski; Chris T. Evelo; Reza Aalizadeh; Hristo Aladjov; Kasia Arturi; Karine Audouze; Pavel Babica; Karel Berka; Jos Bessems; Ludek Blaha; Evan E Bolton; Montserrat Cases; Dimitrios Damalas; Kirtan Dave; Marco Dilger; Thomas Exner; Daan P. Geerke; Roland C. Grafström; Alasdair J. G. Gray; John M. Hancock; Henner Hollert; Nina Jeliazkova; Danyel Jennen; Fab
Published in: F1000Research, 2021, ISSN 2046-1402
Publisher: F1000 Research Ltd.
DOI: 10.12688/f1000research.74502.2

Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements

Author(s): Damir Baranasic; Matthias Hörtenhuber; Piotr J. Balwierz; Tobias Zehnder; Abdul Kadir Mukarram; Chirag Nepal; Csilla Várnai; Yavor Hadzhiev; Ada Jimenez-Gonzalez; Nan Li; Joseph Wragg; Fabio M. D’Orazio; Dorde Relic; Mikhail Pachkov; Noelia Díaz; Benjamín Hernández-Rodríguez; Zelin Chen; Marcus Stoiber; Michaël Dong; Irene Stevens; Samuel E. Ross; Anne Eagle; Ryan Martin; Oluwapelumi Obas
Published in: Nature Genetics, Issue Volume 54, 2022, Page(s) 1037-1050, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-022-01089-w

Evaluating Toxicity of Chemicals using a Zebrafish Vibration Startle Response Screening System

Author(s): Hayot, G., Marcato, D., Cramer von Clausbruch, C. A., Pace, G., Strähle, U., Colbourne, J. K., Pylatiuk, C., Peravali, R., Weiss, C., Scholz, S., Dickmeis, T.
Published in: JoVE, 2024, ISSN 1940-087X
Publisher: MYJoVE Corporation
DOI: 10.3791/66153

Toxicity by descent: A comparative approach for chemical hazard assessment

Author(s): John K. Colbourne, Joseph R. Shaw, Elena Sostare, Claudia Rivetti, Romain Derelle, Rosemary Barnett, Bruno Campos, Carlie LaLone, Mark R. Viant, Geoff Hodges,
Published in: Environmental Advances, Issue Volume 9, 2022, ISSN 2666-7657
Publisher: Elsevier BV
DOI: 10.1016/j.envadv.2022.100287

WeSA: a web server for improving analysis of affinity proteomics data

Author(s): Magdalena M Shtetinska, Juan-Carlos González-Sánchez, Tina Beyer, Karsten Boldt, Marius Ueffing, Robert B Russell
Published in: Nucleic Acids Research, Issue 52, 2024, Page(s) W333-W340, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gkae423

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Author(s): Ada Jimenez‐Gonzalez, Federico Ansaloni, Constance Nebendahl, Ghazal Alavioon, David Murray, Weronika Robak, Remo Sanges, Ferenc Müller, Simone Immler
Published in: Molecular Ecology, Issue 33, 2024, ISSN 0962-1083
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/mec.17296

Modernizing persistence–bioaccumulation–toxicity (PBT) assessment with high throughput animal-free methods

Author(s): Escher, Beate I; Altenburger, Rolf; Blüher, Matthias; Colbourne, John K; Ebinghaus, Ralf; Fantke, Peter; Hein, Michaela; Köck, Wolfgang; Kümmerer, Klaus; Leipold, Sina; Li, Xiaojing; Scheringer, Martin; Scholz, Stefan; Schloter, Michael; Schweizer, Pia-Johanna; Tal, Tamara; Tetko, Igor; Traidl-Hoffmann, Claudia; Wick, Lukas Y; Fenner, Kathrin
Published in: Archives of Toxicology, Issue Volume 97, 2023, Page(s) 1267-1283, ISSN 0340-5761
Publisher: Springer Verlag
DOI: 10.1007/s00204-023-03485-5

Discriminating activating, deactivating and resistance variants in protein kinases

Author(s): Gurdeep Singh, Torsten Schmenger, Juan Carlos Gonzalez-Sanchez, Anastasiia Kutkina, Nina Bremec, Gaurav D. Diwan, Pablo Mozas, Cristina López, Reiner Siebert, Rocio Sotillo, Robert B. Russell
Published in: Genome Medicine, Issue 17, 2025, ISSN 1756-994X
Publisher: BioMed Central
DOI: 10.1186/s13073-025-01564-z

Impact of Biotransformation on Internal Concentrations and Specificity Classification of Organic Chemicals in the Zebrafish Embryo (Danio rerio)

Author(s): Nico Grasse, Riccardo Massei, Bettina Seiwert, Stefan Scholz, Beate I. Escher, Thorsten Reemtsma, Qiuguo Fu
Published in: Environmental Science & Technology, Issue 58, 2024, Page(s) 17898-17907, ISSN 0013-936X
Publisher: American Chemical Society
DOI: 10.1021/acs.est.4c04156

The Role of Epistemic Communities in Formulating EU Policy: The PrecisionTox Project

Author(s): Aleksandra Čavoški, Robert Lee, Laura Holden
Published in: Transnational Environmental Law, Issue 14, 2025, Page(s) 198-223, ISSN 2047-1025
Publisher: Cambridge University Press
DOI: 10.1017/s204710252400027x

Precision toxicology: new approach methodologies for chemical safety

Author(s): Aleksandra Cavoski, John Colbourne, Laura Holden, Robert Lee
Published in: Bio-Science Law Review, Issue Volume 19, Issue 3, 2024, Page(s) 101-107, ISSN 1365-8867
Publisher: Lawtext Publishing Ltd

Daphnia as a Sentinel Species for Environmental Health Protection: A Perspective on Biomonitoring and Bioremediation of Chemical Pollution

Author(s): Muhammad Abdullahi, Xiaojing Li*, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K. Colbourne, and Luisa Orsini
Published in: Environmental Science & Technology, 2022, ISSN 0013-936X
Publisher: American Chemical Society
DOI: 10.1021/acs.est.2c01799

The FAIR Cookbook - the essential resource for and by FAIR doers

Author(s): Philippe Rocca-Serra; Wei Gu; Vassilios Ioannidis; Tooba Abbassi Daloii; Salvador Capella-Gutierrez; Ishwar Chandramouliswaran; Andrea Splendiani; Tony Burdett; Robert T. Giessmann; David Henderson; Dominique Batista; Allyson Lister; Ibrahim Emam; Yojana Gadiya; Lucas Giovanni; Egon Willighagen; Chris Evelo; Alasdair J. G. Gray; Philip Gribbon; Nick Juty; Danielle Welter; Karsten Quast; Paul Peete
Published in: Scientific Data, 2023, ISSN 2052-4463
Publisher: Springer Nature
DOI: 10.1038/s41597-023-02166-3

Perspectives on the Drosophila melanogaster Model for Advances in Toxicological Science

Author(s): Matthew D. Rand, Jason M. Tennessen, Trudy F. C. Mackay, Robert R. H. Anholt
Published in: Current Protocols, 2023, ISSN 2691-1299
Publisher: Wiley
DOI: 10.1002/cpz1.870

The Precision Toxicology initiative

Author(s): The PrecisionTox Consortium
Published in: Toxicology Letters, Issue Volume 383, 2023, Page(s) 33-42, ISSN 0378-4274
Publisher: Elsevier BV
DOI: 10.1016/j.toxlet.2023.05.004

The Place of Law in Technology Transitions: A Case Study from Chemical Risk Assessment

Author(s): Aleksandra Čavoški, Laura Holden, Robert Lee
Published in: Journal of Environmental Law, Issue 37, 2025, Page(s) 97-116, ISSN 0952-8873
Publisher: Oxford University Press
DOI: 10.1093/jel/eqae030

Computational Strategies for Assessing Adverse Outcome Pathways: Hepatic Steatosis as a Case Study

Author(s): Rita Ortega-Vallbona, Martina Palomino-Schätzlein, Laia Tolosa, Emilio Benfenati, Gerhard F. Ecker, Rafael Gozalbes, Eva Serrano-Candelas
Published in: International Journal of Molecular Sciences, Issue 25, 2025, Page(s) 11154, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms252011154

The hologenome of Daphnia magna reveals possible DNA methylation and microbiome-mediated evolution of the host genome

Author(s): Anurag Chaturvedi; Xiaojing Li; Vignesh Dhandapani; Hollie Marshall; Stephen Kissane; Maria Cuenca-Cambronero; Giovanni Asole; Ferriol Calvet; Marina Ruiz-Romero; Paolo Marangio; Roderic Guigó; Daria Rago; Leda Mirbahai; Niamh Eastwood; John K Colbourne; Jiarui Zhou; Eamonn Mallon; Luisa Orsini
Published in: Nucleic Acids Research, Issue Volume 51, Issue 18, 2023, Page(s) 9785-9803, ISSN 1096-6080
Publisher: Oxford University Press
DOI: 10.1093/nar/gkad685

Mixtures of organic micropollutants exacerbated in vitro neurotoxicity of prymnesins and contributed to aquatic toxicity during a toxic algal bloom

Author(s): Beate I. Escher, Jörg Ahlheim, Alexander Böhme, Dietrich Borchardt, Werner Brack, Georg Braun, John K. Colbourne, Janek Paul Dann, Joern Gessner, Annika Jahnke, Maria König, Nils Klüver, Martin Krauss, Jungeun Lee, Xiaojing Li, Stefan Lips, Luisa Orsini, Karsten Rinke, Mechthild Schmitt-Jansen, Stefan Scholz, Tobias Schulze, Stephanie Spahr, Nadin Ulrich, Markus Weitere, Elisabeth Varga
Published in: Nature Water, Issue 2, 2024, Page(s) 889-898, ISSN 2731-6084
Publisher: Springer Nature
DOI: 10.1038/s44221-024-00297-4

Utilizing Omics Data for Chemical Grouping

Author(s): Mark R. Viant, Rosemary E. Barnett, Bruno Campos, John K. Colbourne, Marianne Barnard, Adam D. Biales, Mark T. D. Cronin, Kellie A. Fay, Kara Koehrn, Helen F. McGarry, Magdalini Sachana, Geoff Hodges
Published in: Environmental Toxicology and Chemistry, Issue 43, 2025, Page(s) 2094-2104, ISSN 0730-7268
Publisher: Society of Environmental Toxicology and Chemistry
DOI: 10.1002/etc.5959

Uptake and Biotransformation of the Tire Rubber-derived Contaminants 6-PPD and 6-PPD Quinone in the Zebrafish Embryo (Danio rerio)

Author(s): Nico Grasse, Bettina Seiwert, Riccardo Massei, Stefan Scholz, Qiuguo Fu, Thorsten Reemtsma
Published in: Environmental Science & Technology, Issue 57, 2023, Page(s) 15598-15607, ISSN 0013-936X
Publisher: American Chemical Society
DOI: 10.1021/acs.est.3c02819

Balancing chemical safety and animal welfare considerations in the application of new approach methodologies for chemical safety assessment

Author(s): Aleksandra Čavoški, Laura Holden, Leonie Mueller, Robert Lee
Published in: NAM Journal, Issue 1, 2025, Page(s) 100013, ISSN 3050-6204
Publisher: Elsevier BV
DOI: 10.1016/j.namjnl.2025.100013

Improving In Vitro Bioassays: Addressing Chemical Transformation and Baseline Toxicity

Author(s): Huchthausen, Julia
Published in: Issue 1, 2024
Publisher: Eberhard Karls Universität Tübingen
DOI: 10.15496/publikation-95042

FAIR by design: study design-driven creation of standards compliant metadata

Author(s): Batista, Dominique; Jones, Martin; Weber, Ralf; Rocca-Serra, Philippe; Sansone, Susanna-Assunta
Published in: 2023
Publisher: Zenodo
DOI: 10.5281/zenodo.7847620

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