Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1007/s00204-023-03522-3
Licence creative commons licence
Title (Primary) Applying genomics in regulatory toxicology: a report of the ECETOC workshop on omics threshold on non-adversity
Author Gant, T.W.; Auerbach, S.S.; von Bergen, M.; Bouhifd, M.; Botham, P.A.; Caiment, F.; Currie, R.A.; Harrill, J.; Johnson, K.; Li, D.; Rouquie, D.; van Ravenzwaay, B.; Sistare, F.; Tralau, T.; Viant, M.R.; van de Laan, J.W.; Yauk, C.
Source Titel Archives of Toxicology
Year 2023
Department MOLSYB
Volume 97
Issue 8
Page From 2291
Page To 2302
Language englisch
Topic T9 Healthy Planet
Keywords PODS; Transcriptomics; Workshop; ECETOC
Abstract In a joint effort involving scientists from academia, industry and regulatory agencies, ECETOC’s activities in Omics have led to conceptual proposals for: (1) A framework that assures data quality for reporting and inclusion of Omics data in regulatory assessments; and (2) an approach to robustly quantify these data, prior to interpretation for regulatory use. In continuation of these activities this workshop explored and identified areas of need to facilitate robust interpretation of such data in the context of deriving points of departure (POD) for risk assessment and determining an adverse change from normal variation. ECETOC was amongst the first to systematically explore the application of Omics methods, now incorporated into the group of methods known as New Approach Methodologies (NAMs), to regulatory toxicology. This support has been in the form of both projects (primarily with CEFIC/LRI) and workshops. Outputs have led to projects included in the workplan of the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) group of the Organisation for Economic Co-operation and Development (OECD) and to the drafting of OECD Guidance Documents for Omics data reporting, with potentially more to follow on data transformation and interpretation. The current workshop was the last in a series of technical methods development workshops, with a sub-focus on the derivation of a POD from Omics data. Workshop presentations demonstrated that Omics data developed within robust frameworks for both scientific data generation and analysis can be used to derive a POD. The issue of noise in the data was discussed as an important consideration for identifying robust Omics changes and deriving a POD. Such variability or “noise” can comprise technical or biological variation within a dataset and should clearly be distinguished from homeostatic responses. Adverse outcome pathways (AOPs) were considered a useful framework on which to assemble Omics methods, and a number of case examples were presented in illustration of this point. What is apparent is that high dimension data will always be subject to varying processing pipelines and hence interpretation, depending on the context they are used in. Yet, they can provide valuable input for regulatory toxicology, with the pre-condition being robust methods for the collection and processing of data together with a comprehensive description how the data were interpreted, and conclusions reached.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=27173
Gant, T.W., Auerbach, S.S., von Bergen, M., Bouhifd, M., Botham, P.A., Caiment, F., Currie, R.A., Harrill, J., Johnson, K., Li, D., Rouquie, D., van Ravenzwaay, B., Sistare, F., Tralau, T., Viant, M.R., van de Laan, J.W., Yauk, C. (2023):
Applying genomics in regulatory toxicology: a report of the ECETOC workshop on omics threshold on non-adversity
Arch. Toxicol. 97 (8), 2291 - 2302