Mathematical models within the General Unified Threshold models of Survival (GUTS) framework translate time‐variable chemical exposure information into expected survival of animals. The GUTS models are species and compound specific and explicitly describe the internal exposure dynamics in an organism (toxicokinetics) and the related damage and effect dynamics (toxicodynamics), thereby connecting the external exposure concentration dynamics with the simulated mortality or immobility over time. In a recent scientific opinion on toxicokinetic–toxicodynamic (TKTD) models published by the European Food Safety Authority (EFSA), the GUTS modeling framework was considered ready for use in the aquatic risk assessment for pesticides and aquatic fauna. The GUTS models are suggested for use in risk assessment, if they are sufficiently validated for a specific substance–species combination. This paper aims to illustrate how they can be used in the regulatory environmental risk assessment for pesticides for a specific type of refinement, that is, when risks are triggered by lower tiers in acute as well as in chronic risk assessment and mortality or immobility is the critical endpoint. This approach involves the evaluation of time‐variable exposure regimes in a so‐called “Tier‐2C” assessment. The insecticide chlorpyrifos was selected as an example compound because a large data set was available. The GUTS models for 13 different freshwater arthropods and 8 different theoretical aquatic exposure profiles were used to calculate a series of GUTS‐based risk estimates, including exposure profile‐specific multiplication factors leading to 50% mortality or immobility at the end of the tested profile (LP50/EP50) as “margins of safety.” To put the use of GUTS models within the tiered aquatic risk assessment into perspective, GUTS models for the 13 aquatic arthropods were also used to predict the environmental risks of a measured chlorpyrifos exposure profile from an experimental ditch study (Tier‐3 approach), and the results are discussed in the context of calibration of the tiered approach. Integr Environ Assess Manag 2021;17:243–258. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

中文翻译：

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生存模型的通用统一阈值模型在管制水生农药风险评估中的应用，并以杀虫剂毒死rif为例说明。

通用生存统一阈值（GUTS）框架内的数学模型将时变化学暴露信息转化为动物的预期生存。GUTS模型具有物种和化合物特异性，并明确描述了生物体内的内部暴露动态（毒物动力学）以及相关的损害和效应动态（毒物动力学），从而将外部暴露浓度动态与模拟的死亡率或固定性联系起来。在欧洲食品安全局（EFSA）发布的有关毒物动力学-毒物动力学（TKTD）模型的最新科学意见中，认为GUTS建模框架已准备就绪，可用于农药和水生动物的水生风险评估。建议使用GUTS模型进行风险评估，是否已针对特定物质-物种组合进行了充分验证。本文旨在说明如何将其用于特定精制类型的农药的法规环境风险评估，即当急性和慢性风险评估中的较低层次触发风险，而死亡率或固定性是关键端点。这种方法涉及在所谓的“ Tier-2C”评估中评估随时间变化的暴露制度。选择杀虫剂毒死rif作为示例化合物，因为可获得大量数据。用于13种不同淡水节肢动物和8种不同理论水生暴露特征的GUTS模型用于计算一系列基于GUTS的风险估计，包括特定于暴露特征的倍增因子，导致在测试特征（LP50 / EP50）结束时导致50％的死亡率或固定性，称为“安全裕度”。为了将GUTS模型在分层水生风险评估中的使用放到视野中，还通过实验性沟渠研究（Tier-3方法）使用了13种水生节肢动物的GUTS模型来预测毒死rif暴露量的环境风险。在校准分层方法的上下文中讨论了结果。整合环境评估管理2021; 17：243–258。©2020作者。Wiley Periodicals LLC代表环境毒理化学协会（SETAC）发布的《综合环境评估与管理》