Globally implemented ecological risk assessment (ERA) guidelines marginalize hormesis, a biphasic dose–response relationship characterized by low-dose stimulation and high-dose inhibition. The present study illuminated the promise of hormesis as a scientific dose–response model for ERA of per- and polyfluoroalkyl substances (PFAS) represented by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). A total of 266 hormetic dose–response relationships were recompiled from 1237 observations, covering 30 species from nine representative taxonomic groups. The standardized hormetic amplitudes followed the log-normal probability distribution, being subject to the limits of biological plasticity but independent of stress inducers. The SHapley Additive exPlanations algorithm revealed that the target endpoint was the most important variable explaining the hormetic amplitudes. Subsequently, quantitative frameworks were established to incorporate hormesis into the predicted no-effect concentration levels, with a lower induction dose and a zero-equivalent point but a broader hormetic zone for PFOS. Realistically, 10,117 observed concentrations of PFOA and PFOS were gathered worldwide, 4% of which fell within hormetic zones, highlighting the environmental relevance of hormesis. Additionally, the hormesis induction potential was identified in other legacy and emerging PFAS as well as their alternatives and mixtures. Collectively, it is time to incorporate the hormesis concept into PFAS studies to facilitate more realistic risk characterizations.

中文翻译：

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针对全氟烷基和多氟烷基物质引起的兴奋作用的时机已经成熟：全球水生热点及其对生态风险评估的影响


全球实施的生态风险评估（ERA）指南将毒物兴奋效应边缘化，这是一种以低剂量刺激和高剂量抑制为特征的双相剂量反应关系。本研究阐明了毒物兴奋效应作为以全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）为代表的全氟烷基物质和多氟烷基物质（PFAS）ERA的科学剂量反应模型的前景。根据 1237 个观察结果重新编译了总共 266 个毒效剂剂量反应关系，涵盖来自 9 个代表性分类群的 30 个物种。标准化毒物兴奋振幅遵循对数正态概率分布，受到生物可塑性的限制，但与应激诱导因素无关。 SHapley Additive exPlanations 算法表明，目标终点是解释毒物兴奋幅度的最重要变量。随后，建立了定量框架，将毒物兴奋效应纳入预测的无效应浓度水平，其中 PFOS 具有较低的诱导剂量和零当量点，但具有更宽的毒物兴奋效应区域。实际上，全球范围内收集了 10,117 个观察到的 PFOA 和 PFOS 浓度，其中 4% 位于毒物兴奋效应区域内，这凸显了毒物兴奋作用的环境相关性。此外，在其他传统和新兴 PFAS 及其替代品和混合物中也发现了毒物兴奋效应诱导潜力。总的来说，是时候将毒物兴奋效应概念纳入 PFAS 研究中，以促进更现实的风险特征描述。