A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA)

David E. Hines; Stephen W. Edwards; Rory B. Conolly; Annie M. Jarabek

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A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA)

机译：总体暴露途径（AEP）和不良结果途径（AOP）框架在促进人类健康和生态终点整合的累积风险评估（CRA）中的案例研究

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src="http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/esthag/2018/esthag.2018.52.issue-2/acs.est.7b04940/20180111/images/medium/es-2017-04940a_0004.gif">Cumulative risk assessment (CRA) methods promote the use of a conceptual site model (CSM) to apportion exposures and integrate risk from multiple stressors. While CSMs may encompass multiple species, evaluating end points across taxa can be challenging due to data availability and physiological differences among organisms. Adverse outcome pathways (AOPs) describe biological mechanisms leading to adverse outcomes (AOs) by assembling causal pathways with measurable intermediate steps termed key events (KEs), thereby providing a framework for integrating data across species. In this work, we used a case study focused on the perchlorate anion (ClO₄–) to highlight the value of the AOP framework for cross-species data integration. Computational models and dose–response data were used to evaluate the effects of ClO₄– in 12 species and revealed a dose–response concordance across KEs and taxa. The aggregate exposure pathway (AEP) tracks stressors from sources to the exposures and serves as a complement to the AOP. We discuss how the combined AEP-AOP construct helps to maximize the use of existing data and advances CRA by (1) organizing toxicity and exposure data, (2) providing a mechanistic framework of KEs for integrating data across human health and ecological end points, (3) facilitating cross-species dose–response evaluation, and (4) highlighting data gaps and technical limitations.

机译：src =“ http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/esthag/2018/esthag.2018.52.issue-2/acs.est.7b04940/20180111/images/medium /es-2017-04940a_0004.gif“>累积风险评估（CRA）方法促进使用概念性站点模型（CSM）来分配风险并整合来自多个压力源的风险。虽然CSM可能包含多个物种，但是由于数据的可用性和生物体之间的生理差异，评估整个分类单元的终点可能具有挑战性。不良结果途径（AOP）通过将因果途径与可测量的中间步骤（称为关键事件（KE））组合起来，从而描述了导致不良结果（AOs）的生物学机制，从而提供了跨物种整合数据的框架。在这项工作中，我们使用了一个针对高氯酸根阴离子（ClO _{4 – ）的案例研究，以强调AOP框架对于跨物种数据集成的价值。计算模型和剂量反应数据被用来评估ClO _{4 – 对12种物种的影响，并揭示了KEs和类群之间的剂量反应一致性。总暴露途径（AEP）跟踪从源头到暴露的压力源，并作为AOP的补充。我们将讨论组合的AEP-AOP构造如何通过（1）组织毒性和暴露数据，（2）提供KE的机制框架以整合跨人类健康和生态终点的数据来最大程度地利用现有数据并提高CRA，（3）促进跨物种的剂量反应评估，以及（4）强调数据差距和技术局限性。}}

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《Environmental Science & Technology》 |2018年第2期|839-849|共11页
作者
David E. Hines; Stephen W. Edwards; Rory B. Conolly; Annie M. Jarabek;
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作者单位

U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27709, United States;

U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27709, United States;

U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27709, United States;

U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Research Triangle Park, North Carolina 27709, United States;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Application of a combined aggregate exposure pathway and adverse outcome pathway (AEP-AOP) approach to inform a cumulative risk assessment: A case study with phthalates [J] . Clewell Rebecca A., Leonard Jeremy A., Nicolas Chantel I, Toxicology in vitro: an international journal published in association with BIBRA . 2020,第1期

机译：合并骨料暴露途径和不良结果途径（AEP-AOP）方法的应用通知累积风险评估：邻苯二甲酸盐的案例研究
2. A Quantitative Source-to-Outcome Case Study To Demonstrate the Integration of Human Health and Ecological End Points Using the Aggregate Exposure Pathway and Adverse Outcome Pathway Frameworks [J] . Hines David E., Conolly Rory B., Jarabek Annie M. Environmental Science & Technology . 2019,第18期

机译：定量的从源头到结果的案例研究，以使用总体暴露途径和不良结果途径框架展示人类健康与生态终点的整合
3. Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment [J] . Holly M. Mortensen, John Chamberlin, Bonnie Joubert, Mammalian genome: official journal of the International Mammalian Genome Society . 2018,第1a2期

机译：利用人类遗传和不良结果途径（AOP）数据，以提供人体健康风险评估的易感性
4. A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment [C] . D. E. Hines, S. W. Edwards, R. B. Conolly, Annual conference of the International Society of Exposure Science . 2017

机译：案例研究说明了总体暴露途径和不良结果途径框架在将人类健康和生态数据纳入累积风险评估中的效用
5. Quantification of Human Health Risks in Longitudinal Studies from Multimedia Exposure Pathways. [D] . Kundu, Arti. 2013

机译：从多媒体暴露途径进行的纵向研究中人类健康风险的量化。
6. A case study application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to facilitate the integration of human health and ecological endpoints for Cumulative Risk Assessment (CRA) [O] . David E. Hines, Stephen W. Edwards, Rory B. Conolly, -1

机译：总体暴露途径（AEP）和不良结果途径（AOP）框架的案例研究应用以促进人类健康和生态终点的整合以进行累积风险评估（CRA）
7. A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA) [O] . -1

机译：综合曝光途径（AEP）和不良结果途径（AOP）框架的案例研究应用，促进累积风险评估人体健康和生态终点的整合（CRA）

A Case Study Application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Facilitate the Integration of Human Health and Ecological End Points for Cumulative Risk Assessment (CRA)

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