Mechanisms of interactions of hypoxia and temperature with metal stress in fish

拟议的研究的总体目标是获得缺氧和温度与金属胁迫之间的相互作用的机制的理解，更好地评估金属在水生系统中的风险。水生生物通常受到多种压力的影响，这些压力可能相互作用，改变生理反应。然而，现存的风险评估协议主要是基于单一的压力源，一种方法，不能考虑到并发的压力源的相互作用和变化的反应与条件的曝光。事实上，美国环境保护署（美国环保署）已确定压力之间的相互作用机制的认识不足的主要障碍，发展有效的风险评估工具，以保护水生生物。特别令人关切的是，共同发生的应激源可能会导致相加或协同毒理学反应，导致在低于目前评估程序预测的应激源浓度下对环境产生影响。在这些压力源中，自然现象或人类活动和全球气候变化导致的缺氧和温度波动是水生系统中常见的。因此，为了更准确地评估和预测污染物对水生系统造成的风险，有必要清楚地了解这些压力因素的混杂影响。本申请旨在了解缺氧和温度与鱼类金属胁迫的相互作用。目标是：（i）阐明金属、缺氧和热应力相互作用的机制，以确定不受环境溶解氧和温度波动影响的敏感的金属特异性毒理学终点，（ii）确定在同时发生缺氧和/或温度应力期间金属毒性改变的原因和机制，和（iii）确定与生态风险评估中使用的毒性适合度终点相关的生物化学扰动。拟议的研究将有助于实现我的研究计划的长期目标-有效的和科学的防御工具，以监测，预测和调节金属的环境影响的发展。

The overall goal of the proposed research is to gain mechanistic understanding of the interactions between hypoxia and temperature with metals stress for better assessment of metals risk in aquatic systems. Aquatic organisms are generally impacted by multiple stressors that may interact with each other to alter physiological responses. However, extant risk assessment protocols are based largely on data from single stressors, an approach that fails to account for interactive effects of concurrent stressors and variation of responses with conditions of exposure. Indeed, inadequate understanding of the mechanisms of interactions between stressors has been identified by the United States Environmental Protection Agency (U.S. EPA) as a major obstacle to the development of effective risk assessment tools to protect aquatic life. Of particular concern is the fact that co-occurring stressors can cause additive or synergistic toxicological responses resulting in environmental impacts at lower stressor concentrations than predicted by current assessment procedures. Among these stressors, hypoxia and temperature fluctuations resulting from natural phenomena or human activities and global climate change are commonly encountered in aquatic systems. A clear understanding of the confounding effects of these stressors is therefore necessary for more accurate assessment and prediction of the risk posed by pollutants in aquatic systems. This application seeks to understand interactions of hypoxia and temperature with metals stress in fish. The objectives are: (i) to elucidate the mechanisms of interactions of metals, hypoxia and thermal stress with a view to identifying sensitive metal-specific toxicological endpoints that are immune to fluctuations in environmental dissolved oxygen and temperature, (ii) to identify the causes and mechanisms of altered metals toxicity during concurrent hypoxia and/or temperature stress, and (iii) to identify biochemical perturbations that correlate with fitness endpoints of toxicity used in ecological risk assessment. The proposed research will contribute to the realization of the long term goal of my research program- the development of effective and scientifically defensible tools to monitor, predict and regulate environmental impacts of metals.