Claire Beausoleil , Anne Thébault , Patrik Andersson , Nicolas J. Cabaton , Sibylle Ermler , Bernard Fromenty , Clémentine Garoche , Julian L. Griffin , Sebastian Hoffmann , Jorke H. Kamstra , Barbara Kubickova , Virissa Lenters , Vesna Munic Kos , Nathalie Poupin , Sylvie Remy , Maria Sapounidou , Daniel Zalko , Juliette Legler , Miriam N. Jacobs , Christophe Rousselle
{"title":"Weight of evidence evaluation of the metabolism disrupting effects of triphenyl phosphate using an expert knowledge elicitation approach","authors":"Claire Beausoleil , Anne Thébault , Patrik Andersson , Nicolas J. Cabaton , Sibylle Ermler , Bernard Fromenty , Clémentine Garoche , Julian L. Griffin , Sebastian Hoffmann , Jorke H. Kamstra , Barbara Kubickova , Virissa Lenters , Vesna Munic Kos , Nathalie Poupin , Sylvie Remy , Maria Sapounidou , Daniel Zalko , Juliette Legler , Miriam N. Jacobs , Christophe Rousselle","doi":"10.1016/j.taap.2024.116995","DOIUrl":null,"url":null,"abstract":"<div><p>Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (<em>e.g.</em> human, <em>in vivo</em>, <em>in vitro</em> or <em>in silico</em>) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a “suspected MDC” with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"489 ","pages":"Article 116995"},"PeriodicalIF":3.3000,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X24001935","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g. human, in vivo, in vitro or in silico) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a “suspected MDC” with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.
期刊介绍:
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.