INTRODUCTION

Regulatory decisions surrounding chemical safety are based on human and environmental (ecological) protection goals. Historically, such decisions have relied on data from animal toxicity testing to inform hazard and risk assessment and determine whether chemicals pose a threat to human or environmental health. Traditionally, mammalian toxicity test data have driven human health considerations, and studies from select species representing different taxa have driven ecological considerations. Crosstalk and collaboration between human and ecological health knowledge-streams have been limited. This represents a barrier for realizing the ultimate protection goal, which is the health of the planet and all its inhabitants, as exemplified by the One Health approach (https://www.cdc.gov/onehealth/). However, there are global efforts within governments, nongovernmental organizations, academic research organizations, and industry sectors to bridge this gap and focus on achieving optimal health outcomes without the need for animal testing through recognition of the interconnectedness between people and all species that share the environment. With this in mind, it is recognized that focused and concerted efforts to advance methods for cross-species extrapolation that leverage existing toxicity data from both mammals and other model organisms can be used to protect all species.

To expedite the development and regulatory acceptance of computational methods, particularly bioinformatics, for informing cross-species extrapolation for the evaluation of chemical safety, there is a need to bring together tool/database/method developers and regulators in a global cross-sector collaborative consortium. These collaborations will help define regulatory needs, spark the creation of a bioinformatics toolbox, demonstrate the utility of various tools through coordinated application, and enhance communications with various stakeholders. The International Consortium to Advance Cross-Species Extrapolation in Regulation (ICACSER; https://www.setac.org/page/scixspecies) is being developed to align with both the One Health approach and the shifting paradigm in regulatory toxicology articulated by the National Research Council in 2007. Specifically, a strategy was described to include more efficient and cost-effective toxicity testing that takes advantage of cell-based and computational approaches for evaluating chemical safety in the 21st century (National Research Council, 2007). Such methods move away from the whole-animal testing that historically focused on apical endpoints, such as reproduction, growth, development, and mortality, toward testing molecular-, cellular-, and organ-level changes that can be predictive of upstream apical changes in biology and used for regulatory decision-making (National Research Council, 2007). It was envisioned that such a shift in toxicology would simultaneously reduce animal use. The objective of the present Focus article was to describe the challenges surrounding cross-species extrapolation in regulation and introduce new approach methods (NAMs) in bioinformatics that can enhance and broaden the ability to extrapolate toxicity knowledge beyond model organisms to the diversity of species through efforts lead by the developing ICACSER (Textbox 1).

TEXTBOX 1.. Coming to terms

Term	Definition
Adverse outcome pathway	Conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event (e.g., a molecular interaction between a xenobiotic and a specific biomolecule) and an adverse outcome at a biological level of organization relevant to risk assessment.
Bioinformatics	The collection, organization, storage, analysis, and synthesis of biological information using computers commonly applied to -omics data such as molecular genetics, genomics, and proteomics.
Cytotoxic burst	Stress responses are activated in a nonspecific way at concentrations close to cell death.
One Health	Collaborative effort of multiple disciplines—working locally, nationally, and globally—to attain optimal health for people, animals, and the environment.
Species extrapolation	The act of using existing knowledge about one species to estimate, predict, project, or infer the effect, impact, or trajectory of another species.
Species sensitivity distribution	A cumulative probability distribution of a chemical's toxicity measurements obtained from single-species bioassays of various species that can be used to estimate the ecotoxicological impacts of a chemical.
Systematic literature review	A predefined, systematic method whereby literature is assembled, reviewed, and assessed using standardized techniques.
Taxonomic domain of applicability	In the context of the adverse outcome pathway framework, it defines how broadly across taxa/species/subspecies the pathway knowledge is applicable based on conservation of structure and function.
Toxicokinetics	The rate of uptake, excretion, and metabolism of a chemical in an organism.
Toxicodynamics	The dynamic interaction of a chemical with a biological target resulting in a biological effect.
New approach methodologies (NAMs)	An umbrella term used to capture approaches or assays that reduce animal use and improve toxicokinetic or toxicodynamic knowledge of chemicals. They include in silico, in chemico, in vitro assays, omics, and toxicokinetic and exposure prediction.
Metabarcoding	The barcoding of DNA/RNA for the simultaneous identification of many taxa within the same sample.
Organisation for Economic Co-operation and Development (OECD)	An intergovernmental economic organisation with 37 member countries that works cooperatively to establish evidence-based international standards and find solutions to an array of social, economic, and environmental challenges.
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)	A regulation of the European Union that was adopted to improve the protection of human health and the environment from the risks that can be posed by chemicals.

中文翻译：

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促进化学品在监管毒理学中影响的跨物种外推国际联盟

介绍

围绕化学品安全的监管决策基于人类和环境（生态）保护目标。从历史上看，此类决定依赖于动物毒性测试的数据来为危害和风险评估提供信息，并确定化学品是否对人类或环境健康构成威胁。传统上，哺乳动物毒性测试数据推动了人类健康方面的考虑，而来自代表不同分类群的选定物种的研究推动了生态方面的考虑。人类和生态健康知识流之间的串扰和协作受到限制。这代表了实现最终保护目标的障碍，即地球及其所有居民的健康，如 One Health 方法 (https://www.cdc.gov/onehealth/) 所示。然而，政府内部有全球性的努力，非政府组织、学术研究组织和工业部门通过承认人类与共享环境的所有物种之间的相互联系来弥合这一差距，并专注于实现最佳健康结果，而无需进行动物试验。考虑到这一点，人们认识到，利用来自哺乳动物和其他模式生物的现有毒性数据来推进跨物种外推方法的集中和协调一致的努力可用于保护所有物种。

为了加快计算方法（尤其是生物信息学）的开发和监管接受，以便为评估化学品安全性的跨物种推断提供信息，需要将工具/数据库/方法开发人员和监管机构聚集在一个全球跨部门协作联盟中. 这些合作将有助于确定监管需求，激发生物信息学工具箱的创建，通过协调应用展示各种工具的实用性，并加强与各利益相关者的沟通。促进监管中的跨物种外推国际联盟 (ICACSER; https://www.setac.org/page/scixspecies) 正在开发中，以与“统一健康”方法和国家制定的监管毒理学转变范式保持一致。 2007 年研究委员会。 2007 年）。这些方法从历史上专注于顶端终点（如繁殖、生长、发育和死亡率）的全动物测试转向测试可以预测上游顶端变化的分子、细胞和器官水平的变化。生物学和用于监管决策（国家研究委员会，  2007）。据设想，毒理学的这种转变将同时减少动物的使用。本焦点文章的目的是描述监管中跨物种外推的挑战，并在生物信息学中引入新的方法（NAM），这些方法可以增强和扩大通过努力将毒性知识外推到物种多样性的能力由发展中的 ICACSER（文本框 1）领导。

文本框 1..达成协议

学期	定义
不良后果途径	描述有关直接分子引发事件（例如，异生物质和特定生物分子之间的分子相互作用）与与风险评估相关的组织生物学水平的不利结果之间联系的现有知识的概念结构。
生物信息学	使用计算机收集、组织、存储、分析和合成生物信息，这些计算机通常应用于分子遗传学、基因组学和蛋白质组学等组学数据。
细胞毒爆发	在接近细胞死亡的浓度下，应激反应以非特异性方式被激活。
一个健康	多个学科的协作努力——在本地、全国和全球范围内开展工作——为人类、动物和环境实现最佳健康。
物种外推	利用关于一个物种的现有知识来估计、预测、预测或推断另一物种的影响、影响或轨迹的行为。
物种敏感性分布	从各种物种的单一物种生物测定中获得的化学品毒性测量值的累积概率分布，可用于估计化学品的生态毒理学影响。
系统文献回顾	一种预定义的系统方法，使用标准化技术对文献进行汇编、审查和评估。
适用的分类领域	在不良结果通路框架的背景下，它定义了基于结构和功能保护的通路知识在分类群/物种/亚种中的适用范围。
毒代动力学	化学物质在生物体内的摄取、排泄和代谢率。
毒物动力学	化学物质与生物靶标的动态相互作用导致生物效应。
新方法论（NAM）	一个总称，用于捕捉减少动物使用和提高化学品毒代动力学或毒代动力学知识的方法或测定。它们包括计算机、化学、体外测定、组学以及毒代动力学和暴露预测。
元条形码	DNA/RNA 条形码用于同时识别同一样本中的许多分类群。
经济合作与发展组织 (OECD)	一个拥有 37 个成员国的政府间经济组织，合作建立以证据为基础的国际标准，并为一系列社会、经济和环境挑战寻找解决方案。
化学品注册、评估、授权和限制 (REACH)	欧盟通过的一项法规，旨在改善对人类健康和环境的保护，使其免受化学品可能带来的风险。