Oklahoma State University, Stillwater, Oklahoma, USA.
Penn State Erie, The Behrend College, Erie, Pennsylvania, USA.
Environ Toxicol Chem. 2019 Jan;38(1):27-45. doi: 10.1002/etc.4280. Epub 2018 Dec 11.
Adverse outcome pathways (AOPs) link toxicity across levels of biological organization, and thereby facilitate the development of suborganismal responses predictive of whole-organism toxicity and provide the mechanistic information necessary for science-based extrapolation to population-level effects. Thus far AOPs have characterized various acute and chronic toxicity pathways; however, the potential for AOPs to explicitly characterize indirect, energy-mediated effects from toxicants has yet to be fully explored. Indeed, although exposure to contaminants can alter an organism's energy budget, energetic endpoints are rarely incorporated into ecological risk assessment because there is not an integrative framework for linking energetic effects to organismal endpoints relevant to risk assessment (e.g., survival, reproduction, growth). In the present analysis, we developed a generalized bioenergetics-AOP in an effort to make better use of energetic endpoints in risk assessment, specifically exposure scenarios that generate an energetic burden to organisms. To evaluate empirical support for a bioenergetics-AOP, we analyzed published data for links between energetic endpoints across levels of biological organization. We found correlations between 1) cellular energy allocation and whole-animal growth, and 2) metabolic rate and scope for growth. Moreover, we reviewed literature linking energy availability to nontraditional toxicological endpoints (e.g., locomotor performance), and found evidence that toxicants impair aerobic performance and activity. We conclude by highlighting current knowledge gaps that should be addressed to develop specific bioenergetics-AOPs. Environ Toxicol Chem 2019;38:27-45. © 2018 SETAC.
不利结局途径（AOP）将毒性联系在生物组织的各个层次上，从而促进了亚个体反应的发展，这些反应可预测整个生物体的毒性，并为基于科学的外推到群体水平效应提供了必要的机制信息。到目前为止，AOP 已经描述了各种急性和慢性毒性途径；然而，AOP 明确描述毒物的间接、能量介导效应的潜力尚未得到充分探索。事实上，尽管暴露于污染物会改变生物体的能量预算，但很少将能量终点纳入生态风险评估中，因为没有一个综合框架将能量效应与与风险评估相关的生物体终点（例如，生存、繁殖、生长）联系起来。在本分析中，我们开发了一个广义的生物能量 AOP，以努力在风险评估中更好地利用能量终点，特别是在产生生物体能量负担的暴露情景中。为了评估生物能量 AOP 的经验支持，我们分析了发表的数据，以研究生物组织各个层次的能量终点之间的联系。我们发现了 1）细胞能量分配与整体动物生长，以及 2）代谢率与生长范围之间的相关性。此外，我们回顾了将能量可用性与非传统毒理学终点（例如，运动表现）联系起来的文献，并发现有证据表明毒物会损害有氧表现和活动能力。最后，我们强调了当前应该解决的知识差距，以开发特定的生物能量 AOP。Environ Toxicol Chem 2019;38:27-45。©2018 SETAC。
