ALTEX Pub Date : 2025-01-01 Epub Date: 2025-05-19 DOI: 10.14573/altex.2501201

Maria T Baltazar, Sophie Cable, Richard Cubberley, Nicola J Hewitt, Jade Houghton, Predrag Kukic, Hequn Li, Sophie Malcomber, Beate Nicol, Ruth Pendlington, Ans Punt, Joe Reynolds, Sharon Scott, Sandrine Spriggs, Matthew P Dent

{"title":"Making safety decisions for a sunscreen active ingredient using next-generation risk assessment: Benzophenone-4 case study.","authors":"Maria T Baltazar, Sophie Cable, Richard Cubberley, Nicola J Hewitt, Jade Houghton, Predrag Kukic, Hequn Li, Sophie Malcomber, Beate Nicol, Ruth Pendlington, Ans Punt, Joe Reynolds, Sharon Scott, Sandrine Spriggs, Matthew P Dent","doi":"10.14573/altex.2501201","DOIUrl":"10.14573/altex.2501201","url":null,"abstract":"A next generation risk assessment was carried out to evaluate the safety of benzophenone-4 (BP-4), a UV filter present at 5% in a body lotion, to compare a non-animal approach with a traditional safety assessment based on historical animal data. Exposure characterization indicated that BP-4 is poorly absorbed through the skin, poorly metabolized by the liver, a substrate of influx and efflux transporters, and excreted by the kidney. The resulting physiologically-based kinetic model predicted an upper bound (95th percentile) plasma Cmax of 1.27 μM, and liver and kidney concentrations of 0.32 μM and 0.44 μM, respectively. To characterize bioactivity, in silico and in vitro new approach methodologies were used. Points of departure (PoDs) were derived from four bioactivity platforms, including in vitro pharmacological profiling, CALUX assays, high-throughput transcriptomics, and a cell stress panel. By dividing the in vitro PoDs (PoDNAM) from these assays by the 95th percentile plasma Cmax value, bioactivity exposure ratios (BERs) were calculated. The lowest PoD was from a single gene expression change, and the highest PoD from phenotypic biomarkers using a primary renal cell model. Most BERs were above 11, except for those from gene-level PoDNAM in HepG2 and MCF-7 cells, which were 3.3 and 4.3. These lowest PoDNAM values are linked to gene transcription changes and are likely indicative of adaptive biological activity rather than adverse health effects. This work demonstrates the usefulness of next generation risk assessment in addressing pressing relevant regulatory questions without using animals.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"511-530"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113229","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

Guidance for Good In Vitro Reporting Standards (GIVReSt) - A draft for stakeholder discussion and background documentation. Good体外报告标准指南(GIVReSt) -供利益相关者讨论和背景文件的草案。

ALTEX Pub Date : 2025-01-01 DOI: 10.14573/altex.2507041

Ronit Mohapatra, Marcel Leist, Sonja von Aulock, Thomas Hartung

{"title":"Guidance for Good In Vitro Reporting Standards (GIVReSt) - A draft for stakeholder discussion and background documentation.","authors":"Ronit Mohapatra, Marcel Leist, Sonja von Aulock, Thomas Hartung","doi":"10.14573/altex.2507041","DOIUrl":"https://doi.org/10.14573/altex.2507041","url":null,"abstract":"Reproducibility of cell culture experiments between laboratories needs to be improved by ensuring more complete reporting of methodology in scientific papers. The minimum reporting standards sug-gested here cover various cell culture methods including monolayers, stem cells, organoids, and microphysiological systems (MPS). The standards build on existing guidance like Good Cell Culture Practice (GCCP 2.0) and OECD test reporting guidelines on how to quality-assure in vitro work, focusing on transparency and completeness of reporting. Key elements to be reported include full details of cell source and identity, cell quality control and characterization, materials and reagents used, culture conditions and protocols, experimental design, data analysis, data availability, and legal and ethical aspects. For complex models, additional details need to be provided such as cell ratios, microenvironment conditions, functional characterization, etc. The guidance for Good In Vitro Reporting Standards (GIVReSt) is part of a broader initiative of evidence-based toxicology encompassing the improvement of the quality of in vitro studies for safety assessments and regulatory decisions. In summary, GIVReSt addresses incomplete reporting as a major factor affecting repro-ducibility of cell culture experiments by providing clear standards around transparency and rigor in reporting. The integration of agentic artificial intelligence (AI) is envisioned to streamline compliance checking, providing real-time feedback and accelerating scientific discovery by making high-quality evidence more accessible. This should lead to more reliable cell culture research overall.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":"42 3","pages":"376-396"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651916","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

From cellular perturbation to probabilistic risk assessments. 从细胞扰动到概率风险评估。

ALTEX Pub Date : 2025-01-01 Epub Date: 2025-05-26 DOI: 10.14573/altex.2501291

Alexandra Maertens, Breanne Kincaid, Eric Bridgeford, Celine Brochot, Arthur de Carvalho E Silva, Jean-Lou C M Dorne, Liesbet Geris, Trine Husøy, Nicole Kleinstreuer, Luiz C M Ladeira, Alistair Middleton, Joe Reynolds, Blanca Rodriguez, Erwin L Roggen, Giulia Russo, Kris Thayer, Thomas Hartung

{"title":"From cellular perturbation to probabilistic risk assessments.","authors":"Alexandra Maertens, Breanne Kincaid, Eric Bridgeford, Celine Brochot, Arthur de Carvalho E Silva, Jean-Lou C M Dorne, Liesbet Geris, Trine Husøy, Nicole Kleinstreuer, Luiz C M Ladeira, Alistair Middleton, Joe Reynolds, Blanca Rodriguez, Erwin L Roggen, Giulia Russo, Kris Thayer, Thomas Hartung","doi":"10.14573/altex.2501291","DOIUrl":"10.14573/altex.2501291","url":null,"abstract":"Chemical risk assessment is evolving from traditional deterministic approaches to embrace probabilistic methodologies, where risk of hazard manifestation is understood as a more or less probable event depending on exposure, individual factors, and stochastic processes. This is driven by advancements in human stem cells, complex tissue engineering, high-performance computing, and cheminformatics, and is more recently facilitated by large-scale artificial intelligence models. These innovations enable a more nuanced understanding of chemical hazards, capturing the complexity of biological responses and variability within populations. However, each technology comes with its own uncertainties impacting on the estimation of hazard probabilities. This shift addresses the limitations of point estimates and thresholds that oversimplify hazard assessment, allowing for the integration of kinetic variability and uncertainty metrics into risk models. By leveraging modern technologies and expansive toxicological data, probabilistic approaches offer a comprehensive evaluation of chemical safety. This paper summarizes a workshop held in 2023 and discusses the technological and data-driven enablers, and the challenges faced in their implementation, with particular focus on perturbation of biology as the basis of hazard estimates. The future of toxicological risk assessment lies in the successful integration of these probabilistic models, promising more accurate and holistic hazard evaluations.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"413-434"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153222","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

InViTe2 Retreat: Advancing new approach methodologies in chemical safety testing and drug discovery. 会务会：推进化学安全测试和药物发现的新方法方法。

ALTEX Pub Date : 2025-01-01 DOI: 10.14573/altex.2506301

Chiara Wolfbeisz, Yaroslav Tanaskov, Eike Cöllen, Marlene Hermann, Stefan Jovanovic, Ralph Lipp, Viktoria Magel, Ylea Papatheodorou, Nadine Renner, Jasmin Schäfer, Lea Scherer, Melanie Scherer, Rebecca Wienbruch, Alexander Zielinski, Alina Zubrod

引用次数: 0

Non-animal approaches - Concept, validation, and regulatory acceptance: The fourth Asian Congress of Alternatives to Animal Experiments (4ACAAE) and the seventh Annual Meeting of the Society for Alternatives to Animal Experiments - India (7SAAE-I). 非动物方法-概念，验证和监管接受：第四届亚洲动物实验替代大会（4ACAAE）和第七届动物实验替代学会年会-印度（7SAAE-I）。

ALTEX Pub Date : 2025-01-01 DOI: 10.14573/altex.2505081

Sheikh Raisuddin, Mehjbeen Javed, Suramya Suramya, Mohammad Anas Saifi, Suhel Parvez, Mohammad Abdulkader Akbarsha

引用次数: 0

How evidence-based methodologies can help identify and reduce uncertainty in chemical risk assessment. 基于证据的方法如何帮助识别和减少化学品风险评估中的不确定性。

IF 5.6

ALTEX Pub Date : 2022-01-01 Epub Date: 2022-01-31 DOI: 10.14573/altex.2201131

Sebastian Hoffmann, Paul Whaley, Katya Tsaioun

{"title":"How evidence-based methodologies can help identify and reduce uncertainty in chemical risk assessment.","authors":"Sebastian Hoffmann, Paul Whaley, Katya Tsaioun","doi":"10.14573/altex.2201131","DOIUrl":"https://doi.org/10.14573/altex.2201131","url":null,"abstract":"Evidence-based methodology, in particular systematic review, is increasingly being applied in environmental, public, and occupational health to increase the transparency, comprehensiveness, and objectivity of the processes by which existing evidence is gathered, assessed, and synthesized in answering research questions. This development is also changing risk assessment practices and will impact the assessment of uncertainties in the evidence for risks to human health that are posed by exposure to chemicals. The potential of evidence-based methodology for characterizing uncertainties in risk assessment has been widely recognized, while its contribution to uncertainty reduction is yet to be fully elucidated. We therefore present some key aspects of the evidence-based approach to risk assessment, showing how they can contribute to the identification and the assessment of uncertainties. We focus on the pre-specification of an assessment methodology in a protocol, comprehensive search strategies, study selection using predefined eligibility criteria, critical appraisal of individual studies, and an evidence integration and uncertainty characterization process based on certainty of evidence frameworks that are well-established in health care research. We also provide examples of uncertainty in risk assessment and discuss how evidence-based methodology could address those. This perspective, which neither claims to be comprehensive nor complete, is intended to stimulate discussion of the topic and to motivate detailed exploration of how evidence-based methodology contributes to characterization of uncertainties, and how it will lead to uncertainty reduction in the conduct of health risk assessment.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"175-182"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39573216","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

Potential of concentration-response data to broaden regulatory application of in vitro test guidelines. 浓度反应数据在扩大体外测试准则监管应用方面的潜力。

IF 5.6

ALTEX Pub Date : 2022-01-01 Epub Date: 2021-12-09 DOI: 10.14573/altex.2107091

Miriam N Jacobs, Janine Ezendam, Betty Hakkert, Michael Oelgeschlaeger

{"title":"Potential of concentration-response data to broaden regulatory application of in vitro test guidelines.","authors":"Miriam N Jacobs, Janine Ezendam, Betty Hakkert, Michael Oelgeschlaeger","doi":"10.14573/altex.2107091","DOIUrl":"https://doi.org/10.14573/altex.2107091","url":null,"abstract":"International chemical regulatory activities are moving towards new approach methodology and away from traditional animal-based models, shifting and expanding from one single in vivo assay towards combined use of different in vitro assays within integrated approaches for testing and assessment and defined approaches to serve hazard identification, classification and selection of points of departure for risk assessment. Whilst many in vitro test guidelines were developed against specific hazard cut-off values, quantitative information is needed in data interpretation procedures for potency assessment purposes or to define points of departure so that assays can fulfill evolving regulatory needs. Utilizing four examples from skin sensitization, phototoxicity, endocrine activity, and non-genotoxic carcinogenicity, we illustrate why a shift in data generation and data interpretation procedures is needed to facilitate the full exploitation of the data that is generated using these assays. This requires the development of a practical approach that uses or expands upon existing guidance. Experience gained with such an approach can then provide a basis for an overarching strategy in test guideline development that should better facilitate combinations of in vitro test guidelines for specific endpoints that will be more transparent, robust, and adaptable for specific regulatory purposes.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"315–321"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39582577","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: 3

On the usefulness of animals as a model system (part II): Considering benefits within distinct use domains. 关于动物作为模型系统的有用性(第二部分):在不同的使用领域内考虑利益。

IF 5.6

ALTEX Pub Date : 2022-01-01 DOI: 10.14573/altex.2207111

Giorgia Pallocca, Marcel Leist

{"title":"On the usefulness of animals as a model system (part II): Considering benefits within distinct use domains.","authors":"Giorgia Pallocca, Marcel Leist","doi":"10.14573/altex.2207111","DOIUrl":"https://doi.org/10.14573/altex.2207111","url":null,"abstract":"In many countries, animal experiments can only be performed when their necessity has been demonstrated in a legal document. As the usefulness of animals in research is also a significant societal and political issue, criteria to structure debates and evaluations are needed. Here, background information is given on laboratory animal studies. Moreover, parameters that may be considered in judging their usefulness are suggested. The discussion is strictly focused on animals used as tools/test systems/models to provide information on humans. In this context, general features and performance characteristics of models are discussed. Examples are given for well-recognized criteria (e.g., robustness, relevance, predictivity) to judge the usefulness of predictive models. The main hypothesis put forward here is that a benefits evaluation (usefulness metrics) is only possible within sharply circumscribed \"use domains\". Examples are given for the research fields of drug and vaccine research, toxicology, disease pathogenesis, and basic biological research. Efficacy, safety, and quality studies are highlighted as \"use domains\" within the field of drug discovery and production. A further separation into individual diseases, drug targets or symptoms is suggested for, e.g., efficacy studies or pathophysiology. Finally, an outlook is given on the evaluation of model advantages and disadvantages to arrive at their \"net benefit\". Moreover, the need to compare the net benefits of animal models versus that of their alternatives is highlighted.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"531-539"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40628999","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: 7

EFSA's framework for evidence-based scientific assessments: A case study on uncertainty analysis. 欧洲食品安全局基于证据的科学评估框架:不确定性分析的案例研究。

IF 5.6

ALTEX Pub Date : 2022-01-01 Epub Date: 2021-06-28 DOI: 10.14573/altex.2004211

Elisa Aiassa, Caroline Merten, Laura Martino

{"title":"EFSA's framework for evidence-based scientific assessments: A case study on uncertainty analysis.","authors":"Elisa Aiassa, Caroline Merten, Laura Martino","doi":"10.14573/altex.2004211","DOIUrl":"https://doi.org/10.14573/altex.2004211","url":null,"abstract":"To provide sound scientific advice in support of the European decision-making process in food and feed safety, the European Food Safety Authority (EFSA) has defined the principles for producing “evidence-based scientific assessments” (impartiality, methodological rigor, transparency, and engagement) and, to help fulfil them, has developed cross-cutting methodological approaches. This paper focusses on two of these approaches: conducting scientific assessments in four steps – with an emphasis on developing a protocol for the assessment a priori – and analyzing uncertainty. An overview of the 4-step approach and of the methods for addressing uncertainty is given, and a case study on uncertainty analysis, developed in collaboration with the German Federal Institute for Risk Assessment, is illustrated. The main advantage related to the implementation of protocols and uncertainty analysis is improvement of the scientific value of the outputs. However, experience and further capacity-building is needed to better incorporate uncertainty analysis into the planning phase (protocol) of the scientific assessment process. The case study is based on exposure in humans. Nonetheless it provides an example of a framework for evidence-based scientific assessments that is applicable also to other types of evidence, including evidence arising from new approach methodologies. Adopting the proposed framework, which covers an analysis of uncertainties in the planning and implementation phase, is expected to foster the integration of multiple evidence sources, including alternative methods and testing strategies, in the regulatory scientific assessment process.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":"451–462"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39119103","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: 2

Predictive alternative methods for assessing biocompatibility of dental materials: A NIST-NIDCR workshop report. 评估牙科材料生物相容性的预测替代方法:NIST-NIDCR研讨会报告。

IF 5.6

ALTEX Pub Date : 2022-01-01 DOI: 10.14573/altex.2206241

Elijah J Petersen, John T Elliott, Simona Bancos, Brittany Caldwell, Sharukh S Khajotia, Nicole C Kleinstreuer, Edward Margerrison, Carmem Pfeifer

引用次数: 2

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