Current opinion in toxicology最新文献

The European Partnership PARC’s role in actively promoting the uptake of new approach methodologies and next-generation risk assessment into regulatory risk assessment practice

IF 4.6

Current opinion in toxicology Pub Date : 2025-01-29 DOI: 10.1016/j.cotox.2025.100517

Matthias Herzler , Mirjam Luijten , Philip Marx-Stoelting , Gilles Rivière

{"title":"The European Partnership PARC’s role in actively promoting the uptake of new approach methodologies and next-generation risk assessment into regulatory risk assessment practice","authors":"Matthias Herzler , Mirjam Luijten , Philip Marx-Stoelting , Gilles Rivière","doi":"10.1016/j.cotox.2025.100517","DOIUrl":"10.1016/j.cotox.2025.100517","url":null,"abstract":"<div><div>Existing approaches for human health risk assessment of chemicals have overall provided a high level of protection for EU citizens. However, the established assessment schemes face numerous challenges. Ethical and scientific concerns about using animals for safety testing have triggered awareness of the need for a paradigm shift, requiring new concepts for chemical risk assessment complementing and, in the long run, replacing existing schemes. Next-Generation Risk Assessment (NGRA) using new approach methodologies (NAMs) is commonly regarded as the way forward. However, adequately meeting regulatory needs is challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) supports the development of NGRA frameworks and their implementation at all levels, from developing adverse outcome pathways (AOPs), NAMs and integrated approaches to testing and assessments (IATAs), to designing new conceptual approaches and formulating strategic roadmaps. A particular strength of PARC is its focus on interaction and collaboration with stakeholders from all sectors of the chemical risk assessment community to promote cooperation, advance research, increase knowledge of chemical risk assessment and train methodological skills. Its results will help launch European and national strategies to reduce risks posed by hazardous chemicals, to reduce animal testing and to implement NGRA strategies in regulatory practice.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"42 ","pages":"Article 100517"},"PeriodicalIF":4.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The key characteristics concept

IF 4.6

Current opinion in toxicology Pub Date : 2024-12-27 DOI: 10.1016/j.cotox.2024.100515

Martyn T. Smith

{"title":"The key characteristics concept","authors":"Martyn T. Smith","doi":"10.1016/j.cotox.2024.100515","DOIUrl":"10.1016/j.cotox.2024.100515","url":null,"abstract":"<div><div>In evaluating whether a chemical can cause cancer or another adverse outcome, three lines of evidence are typically considered: epidemiology, animal bioassays and mechanistic evidence. The key characteristics (KCs) form the basis of a uniform approach for searching, organizing, and evaluating mechanistic evidence to support hazard identification. KCs are the established properties of the toxicants themselves and are generated from our understanding of mechanisms of toxicity. KCs have been published for carcinogens, endocrine disruptors and reproductive, liver immune and cardiovascular toxicants. We noted that several KCs were common to different types of toxicants, whereas others were highly specific. Hence, there may be overlapping umbrella KCs for potentially hazardous bioactive chemicals that could be used in predictive toxicology. There are, however, also clearly unique KCs for chemicals that primarily target a specific organ and these unique KCs could be especially important to predicting target organ toxicity. It is possible that <em>in silico</em> approaches, <em>in vitro</em> tests, and <em>in vivo</em> biomarkers could be developed, which predict the “umbrella” and “unique” KCs of hazardous chemicals. However, given the significance of human evidence, the development of a set of biomarkers that could be used to measure the KCs in molecular epidemiology studies is also important.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"41 ","pages":"Article 100515"},"PeriodicalIF":4.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancements in the developmental zebrafish model for predictive human toxicology

IF 4.6

Current opinion in toxicology Pub Date : 2024-12-24 DOI: 10.1016/j.cotox.2024.100516

Mackenzie L. Morshead, Robyn L. Tanguay

引用次数: 0

Implementing AOPs use for pesticide neurotoxicity assessment

IF 4.6

Current opinion in toxicology Pub Date : 2024-10-29 DOI: 10.1016/j.cotox.2024.100505

Barbara Viviani , Miriam Midali , Melania Maria Serafini , Iris Mangas

{"title":"Implementing AOPs use for pesticide neurotoxicity assessment","authors":"Barbara Viviani , Miriam Midali , Melania Maria Serafini , Iris Mangas","doi":"10.1016/j.cotox.2024.100505","DOIUrl":"10.1016/j.cotox.2024.100505","url":null,"abstract":"<div><div>Due to the unique characteristics of the nervous system, chemical exposures pose significant challenges in establishing definitive links to neurological adverse health effects. The key obstacles to neurotoxicity assessment include the complexity of the nervous system, species differences, extended developmental time, and cumulative exposure risks. Regulatory agencies have long required neurotoxicity testing, which has relied primarily on animal models. With increased mechanistic understanding and technological progress, other approaches become possible that could address some of the limitations of traditional neurotoxicity testing (e.g. high cost, ethical concerns, low precision, or human relevance). Recent international efforts to develop adverse outcome pathways (AOPs) and AOP-informed Integrated Approaches to Testing and Assessment offer new possibilities for neurotoxicity testing and assessment. This mini review highlights the advances, while addressing limitations, in the development and application of AOPs for both adult and developmental neurotoxicity as a way to address shortcomings in regulatory neurotoxicity assessment. Case studies are provided to illustrate the recent successful integration of AOPs into regulatory decision-making for pesticide risk assessment.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"41 ","pages":"Article 100505"},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adverse outcome pathway networks as the basis for the development of new approach methodologies: Liver toxicity as a case study 将不良后果路径网络作为开发新方法的基础：以肝脏毒性为例

IF 4.6

Current opinion in toxicology Pub Date : 2024-09-29 DOI: 10.1016/j.cotox.2024.100504

Mathieu Vinken

引用次数: 0

New approach methodologies (NAMs) in drug safety assessment: A vision of the future 药物安全性评估中的新方法（NAMs）：未来展望

IF 4.6

Current opinion in toxicology Pub Date : 2024-09-04 DOI: 10.1016/j.cotox.2024.100502

Ruth A. Roberts

{"title":"New approach methodologies (NAMs) in drug safety assessment: A vision of the future","authors":"Ruth A. Roberts","doi":"10.1016/j.cotox.2024.100502","DOIUrl":"10.1016/j.cotox.2024.100502","url":null,"abstract":"<div><div>Much progress has been made in reducing and refining animal use in toxicology testing, but progress in the use of new approach methodologies (NAMs) to replace animals is disappointing. There are many highly sophisticated NAMs available, but societal, regulatory and political barriers to their implementation remain. Change requires vision, starting with imagining a future where we are successful. Specifically, this would comprise the registration of safe and effective medicines without animal tests. How do we achieve this vision? Thinking differently, in silico methods could be used to provide a detailed assessment of target- and modality-related toxicological risks, coupled with modelling of exposure. In vitro NAMs such as microphysiological systems, microelectrode array and ion channel panels could then be employed to address hypothetical risks. Finally, the safety of first time in human trials could be assessed and assured using circulating nanobots that measure conventional clinical pathology parameters alongside new biomarkers such as circulating tissue DNA. This may seem the stuff of fantasy, but imagination is key to shaping a better future and all change starts with a vision, however far-fetched it may seem today.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"40 ","pages":"Article 100502"},"PeriodicalIF":4.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial: Transforming toxicology one cell at a time: A special issue on the application of scRNA-seq to the study of environmental response 社论：一次改变一个细胞的毒理学：关于应用 scRNA-seq 研究环境反应的特刊

IF 4.6

Current opinion in toxicology Pub Date : 2024-09-02 DOI: 10.1016/j.cotox.2024.100503

Patrick Allard, Justin A. Colacino, Kristine L. Willett

引用次数: 0

Practical lessons of the 3Rs: Learning from the past and looking toward the future 3Rs 的实践经验：总结过去，展望未来

IF 4.6

Current opinion in toxicology Pub Date : 2024-08-16 DOI: 10.1016/j.cotox.2024.100499

Alan M. Hoberman , Barbara L.F. Kaplan

{"title":"Practical lessons of the 3Rs: Learning from the past and looking toward the future","authors":"Alan M. Hoberman , Barbara L.F. Kaplan","doi":"10.1016/j.cotox.2024.100499","DOIUrl":"10.1016/j.cotox.2024.100499","url":null,"abstract":"<div><p>Replacement, reduction, and refinement, known as the 3Rs, is a well-known and broadly applied concept in biomedical science. Since its formal introduction in 1959, application of the 3Rs have refined approaches to reduce or eliminate distress, reduced overall use through repeated measures approaches and use of appropriate numbers of animals, or have replaced animals altogether. However, adoption of the 3Rs is not always easy, due in part to initial lack of awareness of the importance of animal well-being to the outcome of scientific investigation, a lack of understanding of use of results from <em>in vivo</em> model verses <em>in vitro</em> models, lack of effective communication about model benefits, or other technical issues with the development or use of an assay. In understanding the history of the 3Rs, we can learn from or avoid previous challenges as we look to the future of the application of the 3Rs. For instance, there is little doubt that awareness and use of the 3Rs influenced the concept of new approach methods (NAMs), a term describing assays that include traditional <em>in vitro</em> cultures, microphysiological systems, and <em>in silico</em> approaches, and is certainly part of the 3Rs future and the ultimate replacement of an animal-based assay.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"40 ","pages":"Article 100499"},"PeriodicalIF":4.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in genomic toxicology: In vitro developmental toxicity test based on signal network disruption dynamics 基因组毒理学的进展：基于信号网络中断动力学的体外发育毒性测试

IF 4.6

Current opinion in toxicology Pub Date : 2024-07-14 DOI: 10.1016/j.cotox.2024.100489

Yusuke Okubo , Yoko Hirabayashi , Junji Fukuda

引用次数: 0

NAMs: Beta testing needed NAM：需要测试版

IF 4.6

Current opinion in toxicology Pub Date : 2024-07-14 DOI: 10.1016/j.cotox.2024.100490

Denise Bloch, Philip Marx-Stoelting, Tewes Tralau

{"title":"NAMs: Beta testing needed","authors":"Denise Bloch, Philip Marx-Stoelting, Tewes Tralau","doi":"10.1016/j.cotox.2024.100490","DOIUrl":"10.1016/j.cotox.2024.100490","url":null,"abstract":"<div><p>A variety of new approach methodologies (NAMs) have already been developed for acute systemic and short-term toxicity, including <em>in vitro</em>, <em>in silico</em>, and omics methods. To advance their regulatory implementation, we suggest that beta testing of these methods in regulatory settings is urgently needed. There are several limitations to the use of NAMs for acute systemic and short-term toxicity, such as the lack of definitions for applicability domains, skewed reference data for validation, and the absence of representation of kinetic processes and multi-organ complexity. These limitations may lead to risks associated with the ordinary regulatory implementation, such as the application of methods to substances outside of their intended applicability domain or reduced predictivity due to a lack of mechanistic information or consideration of kinetics. We argue that this could be avoided by beta testing. Further benefits of beta testing would be the filling of <em>in vivo</em> data gaps and potentially improved validation with regard to human relevance of methods. In order to enhance the improvement, familiarisation, and acceptance of NAMs in the near future, it is essential for such concept of beta testing to rely on feedback loops between method testers and developers.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"39 ","pages":"Article 100490"},"PeriodicalIF":4.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468202024000329/pdfft?md5=43c34608e921555b7f5665fb5635a6ef&pid=1-s2.0-S2468202024000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0