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This article discusses the measurement and interpretation of vitellogenin (VTG) in fish and amphibians as a biomarker for endocrine activity. The reliability and acceptability of VTG results are important for regulatory assessments of chemicals. The article highlights the variability in VTG measurements and the need for improvement in sampling, quantification, and data handling. It proposes a decision logic to assist in the interpretation of VTG measurements and calls for the development of OECD guidance on best practices for VTG assessment. The article emphasizes the importance of considering other factors and endpoints in conjunction with VTG results to determine endocrine activity. [Extracted from the article]

In 2012, 20 key questions related to hazard and exposure assessment and environmental and health risks of pharmaceuticals and personal care products in the natural environment were identified. A decade later, this article examines the current level of knowledge around one of the lowest‐ranking questions at that time, number 19: "Can nonanimal testing methods be developed that will provide equivalent or better hazard data compared with current in vivo methods?" The inclusion of alternative methods that replace, reduce, or refine animal testing within the regulatory context of risk and hazard assessment of chemicals generally faces many hurdles, although this varies both by organism (human‐centric vs. other), sector, and geographical region or country. Focusing on the past 10 years, only works that might reasonably be considered to contribute to advancements in the field of aquatic environmental risk assessment are highlighted. Particular attention is paid to methods of contemporary interest and importance, representing progress in (1) the development of methods which provide equivalent or better data compared with current in vivo methods such as bioaccumulation, (2) weight of evidence, or (3) ‐omic‐based applications. Evolution and convergence of these risk assessment areas offer the basis for fundamental frameshifts in how data are collated and used for the protection of taxa across the breadth of the aquatic environment. Looking to the future, we are at a tipping point, with a need for a global and inclusive approach to establish consensus. Bringing together these methods (both new and old) for regulatory assessment and decision‐making will require a concerted effort and orchestration. Environ Toxicol Chem 2024;43:559–574. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Many regulations are beginning to explicitly require investigation of a chemical's endocrine‐disrupting properties as a part of the safety assessment process for substances already on or about to be placed on the market. Different jurisdictions are applying distinct approaches. However, all share a common theme requiring testing for endocrine activity and adverse effects, typically involving in vitro and in vivo assays on selected endocrine pathways. For ecotoxicological evaluation, in vivo assays can be performed across various animal species, including mammals, amphibians, and fish. Results indicating activity (i.e., that a test substance may interact with the endocrine system) from in vivo screens usually trigger further higher‐tier in vivo assays. Higher‐tier assays provide data on adverse effects on relevant endpoints over more extensive parts of the organism's life cycle. Both in vivo screening and higher‐tier assays are animal‐ and resource‐intensive and can be technically challenging to conduct. Testing large numbers of chemicals will inevitably result in the use of large numbers of animals, contradicting stipulations set out within many regulatory frameworks that animal studies be conducted as a last resort. Improved strategies are urgently required. In February 2020, the UK's National Centre for the 3Rs and the Health and Environmental Sciences Institute hosted a workshop ("Investigating Endocrine Disrupting Properties in Fish and Amphibians: Opportunities to Apply the 3Rs"). Over 50 delegates attended from North America and Europe, across academia, laboratories, and consultancies, regulatory agencies, and industry. Challenges and opportunities in applying refinement and reduction approaches within the current animal test guidelines were discussed, and utilization of replacement and/or new approach methodologies, including in silico, in vitro, and embryo models, was explored. Efforts and activities needed to enable application of 3Rs approaches in practice were also identified. This article provides an overview of the workshop discussions and sets priority areas for follow‐up. Integr Environ Assess Manag 2022;18:442–458. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). KEY POINTS: In vivo screening and higher‐tier assays to evaluate a chemical's potential endocrine‐disrupting properties and potential impacts on ecosystems are animal‐ and resource‐intensive and can be technically challenging to conduct.There has been much recent work to develop new approach methodologies (NAMs)—in silico and in vitro approaches—that can be applied in this space.An understanding of the opportunities and challenges with the current in vivo approaches, coupled with the ongoing efforts to expand the development, use, and application of NAMs, will help focus short‐ and long‐term goals.International, multisector science‐based activities provide the framework to improve ecological safety as it relates to compounds with endocrine‐disrupting properties. [ABSTRACT FROM AUTHOR]

ABSTRACT The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals-the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417-421. © 2015 SETAC [ABSTRACT FROM AUTHOR]

The article focuses on a research related to reduction in number of fish in bioconcentraion testing and identification of the related barriers. Topics discussed include bioconcentration tests being conducted according to Organization for Economic Co-operation and Development (OECD) guideline, use of 1-concentration approach for the research and amendment of OECD guideline permitting for testing of 1 concentration and guidelines of the U.S. Environmental Protection Agency.

The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is an independent scientific organization that is based in the United Kingdom, which was set up by the government to lead the discovery and application of new technologies and approaches that minimize the use of animals in research and improve animal welfare. The NC3Rs uses a range of strategies to improve and advance science through application of the 3Rs. These include funding basic research, open innovation (CRACK IT), and programs run by inhouse scientists. We present several case studies from the NC3Rs portfolio, featuring asthma research, the use of nonhuman primates in monoclonal antibody development, and CRACK IT. Finally, we anticipate the future, as we use our experience to move into new research fields and expand toward international collaboration. Here we highlight how equipping scientists with relevant and emerging 3Rs tools can help overcome the challenges and limitations of the use of animals in research to the benefit of the whole bioscience community.