Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – Part IV: the ECETOC and CLE Proposal for a Thyroid Function-Related Neurodevelopmental Toxicity Testing and Assessment Scheme (Thyroid-NDT-TAS)

Melching-Kollmuß, Stephanie; Bothe, Kathrin; Charlton, Alex; Gangadharan, Babunilayam; Ghaffari, Rashin; Jacobi, Sylvia; Marty, Sue; Marxfeld, Heike; McInnes, Elizabeth F.; Sauer, Ursula G.; Sheets, Larry P.; Strupp, Christian; Tinwell, H.; Wiemann, Christiane; Botham, Philip A.; Ravenzwaay, Bennard van

doi:10.1080/10408444.2023.2231033

Critical Reviews in Toxicology

2023

DOI: 10.1080/10408444.2023.2231033

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Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – Part IV: the ECETOC and CLE Proposal for a Thyroid Function-Related Neurodevelopmental Toxicity Testing and Assessment Scheme (Thyroid-NDT-TAS)

Stephanie Melching-Kollmuß¹,

Kathrin Bothe

Alex Charlton

et al.

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Cited by 3 publications

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Evaluating the performance of multi-omics integration: a thyroid toxicity case study

Canzler,

Schubert,

Rolle-Kampczyk

et al. 2024

Arch Toxicol

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Multi-omics data integration has been repeatedly discussed as the way forward to more comprehensively cover the molecular responses of cells or organisms to chemical exposure in systems toxicology and regulatory risk assessment. In Canzler et al. (Arch Toxicol 94(2):371–388. https://doi.org/10.1007/s00204-020-02656-y), we reviewed the state of the art in applying multi-omics approaches in toxicological research and chemical risk assessment. We developed best practices for the experimental design of multi-omics studies, omics data acquisition, and subsequent omics data integration. We found that multi-omics data sets for toxicological research questions were generally rare, with no data sets comprising more than two omics layers adhering to these best practices. Due to these limitations, we could not fully assess the benefits of different data integration approaches or quantitatively evaluate the contribution of various omics layers for toxicological research questions. Here, we report on a multi-omics study on thyroid toxicity that we conducted in compliance with these best practices. We induced direct and indirect thyroid toxicity through Propylthiouracil (PTU) and Phenytoin, respectively, in a 28-day plus 14-day recovery oral rat toxicity study. We collected clinical and histopathological data and six omics layers, including the long and short transcriptome, proteome, phosphoproteome, and metabolome from plasma, thyroid, and liver. We demonstrate that the multi-omics approach is superior to single-omics in detecting responses at the regulatory pathway level. We also show how combining omics data with clinical and histopathological parameters facilitates the interpretation of the data. Furthermore, we illustrate how multi-omics integration can hint at the involvement of non-coding RNAs in post-transcriptional regulation. Also, we show that multi-omics facilitates grouping, and we assess how much information individual and combinations of omics layers contribute to this approach.

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Evaluating the performance of multi-omics integration: a thyroid toxicity case study

Canzler,

Schubert,

Rolle-Kampczyk

et al. 2024

Arch Toxicol

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Endocrine disruption assessment in aquatic vertebrates – Identification of substance-induced thyroid-mediated effect patterns

Lagadic,

Coady,

Körner

et al. 2024

Environment International

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A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment

Vergauwen,

Bajard,

Tait

et al. 2024

Open Res Europe

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Thyroid hormone system disruption (THSD) is a growing concern in chemical hazard assessment due to its impact on human and environmental health and the scarce methods available for assessing the THSD potential of chemicals. In particular, the general lack of validated in silico and in vitro methods for assessing THS activity is of high concern. This manuscript provides an inventory of test methods relevant to THSD. Building on the Organisation for Economic Co-operation and Development (OECD) Guidance Document 150 and recent international developments, we highlight progress in in silico and in vitro methods, as well as in vivo assays. The provided inventory categorizes available methods according to the levels of the OECD Conceptual Framework, with an assessment of the validation status of each method. At Level 1, 12 in silico models that have been statistically validated and are directly related to THSD have been identified. At Level 2, 67 in vitro methods have been listed including those assessed in key initiatives such as the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) validation study to identify potential thyroid disruptors. At Levels 3-5, THSD-sensitive endpoints are being included in existing fish-based OECD Test Guidelines to complement amphibian assays. In total, the inventory counts 108 entries comprising established methods (e.g., OECD Test Guidelines) as well as citable methods that are under further development and in some cases are ready for validation or in the initial stages of validation. This work aims to support the ongoing development of strategies for regulatory hazard assessment, such as integrated approaches to testing and assessment (IATAs), for endocrine disruptors, addressing critical gaps in the current testing landscape for THSD in both human and environmental health contexts.

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Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – Part IV: the ECETOC and CLE Proposal for a Thyroid Function-Related Neurodevelopmental Toxicity Testing and Assessment Scheme (Thyroid-NDT-TAS)

Cited by 3 publications

References 93 publications

Evaluating the performance of multi-omics integration: a thyroid toxicity case study

Evaluating the performance of multi-omics integration: a thyroid toxicity case study

Endocrine disruption assessment in aquatic vertebrates – Identification of substance-induced thyroid-mediated effect patterns

A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment

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