Biotransformation and thyroidogenic effects of organochlorine and organobromine pollutants in avian and mammalian top predator sentinel species

在环境中持久存在和生物积累的人造化学品越来越多地与野生动物和人类的不利影响联系在一起。野生动物发现的许多生物累积性“遗留”和“新出现”污染物含有氯和溴，包括多氯联苯（PCB）和被称为多溴二苯醚（PBDEs）的溴化阻燃剂（BFR）类。有机体从体内消除有机卤素和其他外来化学物质的能力取决于可以介导代谢和生物转化的酶。关于生物转化的作用和意义仍有许多未知之处（例如，在不同物种和食物网中，特别是在顶级捕食者野生动物中，氯化和溴化有机卤素的归宿和生物累积中，包括形成含羟基（OH-）或“酚类”代谢物，存在氧化和脱溴过程。正如多氯联苯和多溴二苯醚在某些野生动物体内的情况所表明的那样，生物转化可导致持久性羟基多氯联苯和羟基多溴二苯醚代谢物，尽管人们对这些“第二级”污染物的形成、生物累积和毒性代谢的了解仍然很少。羟基多氯联苯、羟基多溴二苯醚、相关的酚类化合物/代谢物、多溴二苯醚的脱溴产物和目前使用的溴化阻燃剂通过激素模拟具有“生物活性”，并可干扰甲状腺激素依赖性功能和过程（例如，激素转运和酶介导相互转化）。海洋野生动物这种顶级捕食者积累了大量有机卤素，但其内分泌（甲状腺）活动及其对有机卤素生物转化的影响很少受到关注。拟议的研究将扩大对物种特定作用、机制和环境生态重要性的理解，并开始新的研究，生物转化在命运、生物累积和甲状腺激素运输/相互转换中的重要性，污染物和其他（例如，气候变化）来自五大湖（银鸥）和北极（北极熊和白鸥）的压力。

Man-made chemicals that persist and bioaccumulate in the environment are increasingly being linked to adverse effects in wildlife and humans. Many bioaccumulative "legacy" and "emerging' contaminants found wildlife contain chlorine and bromine, including polychlorinated biphenyls (PCBs) and the brominated flame retardant (BFR) class known as polybrominated diphenyl ethers (PBDEs). An organism's ability to eliminate organohalogens and other foreign chemicals from the body is dependent on enzymes that can mediate metabolism and biotransformation. Much remains unknown as to role and significance of biotransformation (e.g., oxidative and debromination processes) in the fate and bioaccumulation of chlorinated and brominated organohalogens, which includes the formation of hydroxyl- (OH-) containing or "phenolic" metabolites, in different species and food webs, and especially in top predator wildlife. As has been shown for PCBs and PBDEs in some wildlife, biotransformation can lead to persistent OH-PCB and OH-PBDE metabolites, although there remains minimal understanding of the formation, bioaccumulation and toxicokinetics of these "second level" pollutants. OH-PCBs, OH-PBDEs, related phenolic compounds/metabolites, and debrominated products of PBDEs and current-use BFRs are "bioactive" via hormone mimicry, and can interfere with thyroid hormone-dependent functions and processes (e.g., hormone transport and enzyme-mediated inter-conversion). Endocrine (thyroid) activity and effects in relation to organohalogen biotransformation has received minimal attention in top predator, marine wildlife, which accumulate high organohalogen levels. The proposed research will expand the understanding and commence with new research on the species-specific role, mechanisms and environmental ecological importance and significance of biotransformation in the fate, bioaccumulation and thyroid hormone transport/inter-conversion, on legacy and emerging, chlorinated and brominated organics in top-predator wildlife sentinels of contaminant and other (e.g., climate change) stresses from the Great Lakes (herring gulls) and the Arctic (polar bears and glaucous gulls).