Moving from rats to cellular omics in regulatory toxicology: great challenge toward sustainability or “up-shit-creek without a paddle”?

Tralau, Tewes; Luch, Andreas

doi:10.1007/s00204-015-1511-z

Cited by 11 publications

(4 citation statements)

References 16 publications

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“…Where regions member states, is foreseen. Further, the German Federal Institute for Risk Assessment has recently voiced some remarkably progressive positions 13 Tralau and Luch, 2015;Herzler et al, 2021).…”

Section: Challenge 5: How To Open Up Regulators For Change?mentioning

confidence: 99%

A call for a Human Exposome Project

Hartung

2023

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We prevent disease (unfortunately nobody knows how much).-Almost all products should undergo risk assessment.-Toxicology pioneered quality (GLP) and validation (incl. relevance). -Toxicology was the first preclinical science to adapt evidence-based approaches. However, we are not doing a good job selling this. We are the nay-sayers in product development who delay or stop all these fabulous product launches and this typically at a very late stage close to marketing. We are the harbingers of bad news about our food and our environment, the risks that spoil enjoying them. And the discipline of toxicology seems so close to pharmacology that academic chairs are increasingly being IntroductionThe theoretical case for a Human Exposome Project is easy to make. Wouldn't it be wonderful to understand the contribution of exposure to disease? The question is, however, how and is it feasible? But first, why call it a Human Exposome Project and not a Human Toxome Project 1 (Hartung and McBride, 2011)? This has to do with the undeserved mediocre reputation of toxicology, which has already led us to preferentially talk of safety science, risk science, regulatory science, next generation risk assessment, etc. Undeserved, because toxicology is actually big science: -Only a small percentage of disease is genetic, the rest is bad luck and exposure.

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Section: Challenge 5: How To Open Up Regulators For Change?mentioning

confidence: 99%

A call for a Human Exposome Project

Hartung

2023

ALTEX

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“…This is reflected not least by the comparably modest number of validated and internationally accepted alternative methods, none of which harbors a MPS yet. The main obstacles to the implementation of any such methods are, apart from the often slow progress of legal implementation, method validation and an inherent limitation of cellular and MPS to reflect established toxicological endpoints and organism plasticity (Tralau and Luch, 2015). Without changes to long established practices, this makes it difficult to readily adapt such systems for the purpose of quantifiable risk assessments or to transpose the results obtained to the classifications required by the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), Classification, Labelling and Packaging (CLP) or REACH.…”

Section: Selected Legal Framework Regulatory Science and Acceptamentioning

confidence: 99%

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing

Marx¹,

Andersson

Bahinski

et al. 2016

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Summary The recent advent of microphysiological systems – microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro – is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-five experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.

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“…There are also several examples of how omics datasets can be applied to current risk assessment paradigms, including the use of gene set analysis to identify major biological responses after chemical exposure ( Bourdon-Lacombe et al , 2015 ). However, there is still a need for a more complete demonstration of the scientific and practical feasibility of applying these methods directly into human health or ERAs ( ECHA, 2016 ; Margiotta-Casaluci et al , 2016 ; Tralau and Luch, 2015 ).…”

Section: Challenges For Omics In the Aop Framework: Regulatory Acceptmentioning

confidence: 99%

The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment

Brockmeier

Hodges

Hutchinson

et al. 2017

Toxicological Sciences

180

106

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In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework.

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Moving from rats to cellular omics in regulatory toxicology: great challenge toward sustainability or “up-shit-creek without a paddle”?

Cited by 11 publications

References 16 publications

A call for a Human Exposome Project

A call for a Human Exposome Project

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing

The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment

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