Since the early 2000s, biotic ligand models and related constructs have been a dominant paradigm for risk assessment of aqueous metals in the environment. We critically review 1) the evidence for the mechanistic approach underlying metal bioavailability models; 2) considerations for the use and refinement of bioavailability-based toxicity models; 3) considerations for the incorporation of metal bioavailability models into environmental quality standards; and 4) some consensus recommendations for developing or applying metal bioavailability models. We note that models developed to date have been particularly challenged to accurately incorporate pH effects because they are unique with multiple possible mechanisms. As such, we doubt it is ever appropriate to lump algae/plant and animal bioavailability models; however, it is often reasonable to lump bioavailability models for animals, although aquatic insects may be an exception. Other recommendations include that data generated for model development should consider equilibrium conditions in exposure designs, including food items in combined waterborne-dietary matched chronic exposures. Some potentially important toxicity-modifying factors are currently not represented in bioavailability models and have received insufficient attention in toxicity testing. Temperature is probably of foremost importance; phosphate is likely important in plant and algae models. Acclimation may result in predictions that err on the side of protection. Striking a balance between comprehensive, mechanistically sound models and simplified approaches is a challenge. If empirical bioavailability tools such as multiple-linear regression models and look-up tables are employed in criteria, they should always be informed qualitatively and quantitatively by mechanistic models. If bioavailability models are to be used in environmental regulation, ongoing support and availability for use of the models in the public domain are essential. Environ Toxicol Chem 2019;39:60-84. © 2019 SETAC.

中文翻译：

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金属生物利用度模型：当前状态，经验教训，监管使用注意事项和前进的道路。

自2000年代初以来，生物配体模型和相关结构一直是环境中金属水溶液风险评估的主要范例。我们严格地审查1）金属生物利用度模型基础的机械方法的证据；2）考虑使用和完善基于生物利用度的毒性模型；3）将金属生物利用度模型纳入环境质量标准的考虑；4）关于开发或应用金属生物利用度模型的一些共识性建议。我们注意到，迄今为止开发的模型特别难以挑战，因为它们具有多种可能的机制，因此要准确地合并pH值影响。因此，我们怀疑将藻类/植物和动物的生物利用度模型块化是否合适？然而，尽管水生昆虫可能是一个例外，但通常将动物的生物利用度模型放在一起是合理的。其他建议包括为模型开发而生成的数据应考虑暴露设计中的平衡条件，包括与水-饮食匹配的慢性暴露组合食品。目前在生物利用度模型中未表示某些潜在重要的毒性修饰因子，并且在毒性测试中未引起足够的重视。温度可能是最重要的。磷酸盐在植物和藻类模型中可能很重要。适应可能导致保护方面的预测错误。在全面，机械合理的模型与简化方法之间寻求平衡是一个挑战。如果在标准中使用经验生物利用度工具（例如多线性回归模型和查找表），则应始终通过机械模型定性和定量地告知它们。如果要在环境法规中使用生物利用度模型，则在公共领域使用模型的持续支持和可用性至关重要。Environ Toxicol Chem 2019; 39：60-84。©2019 SETAC。