Endocrine disruption by perfluoroalkyl substances and mercury

全氟烷基物质和汞造成的内分泌干扰

• 批准号: 9805082
• 负责人: Mary Ellen Turyk
• 金额: $ 24.02万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9805082
• 关键词: Adult; Affect; Autoantibodies; Benefits and Risks; Biological; Biological Markers; Blood Banks; Blood specimen; Carrier Proteins; Chemical Actions; Chemical Exposure; Chemicals; Cholesterol; Cohort Studies; Consumption; Data; Diabetes Mellitus; Disease; Disease Marker; Elderly; Elements; Endocrine; Endocrine Disruptors; Endocrine System Diseases; Endocrine disruption; Endocrine system; Environmental Pollution; Epidemiology; Estradiol; Exposure to; Fishes; General Population; Glucose; Glycosylated hemoglobin A; Gonadal Steroid Hormones; Gonadotropins; Health; Health Status; High Prevalence; Homeostasis; Hormones; Hyperlipidemia; Hypothyroidism; Incidence; Individual; Intake; Investigation; Iodide Peroxidase; Iodides; Knowledge; Lead; Lipids; Logistics; Longitudinal Studies; Measurement; Measures; Mediation; Mercury; Metabolic; Metals; Modeling; Modification; Nutrient; Obesity; Outcome; Participant; Pathway interactions; Patient Self-Report; Pharmacologic Substance; Pituitary Hormones; Poly-fluoroalkyl substances; Polychlorinated Biphenyls; Population; Prediabetes syndrome; Predisposition; Public Health; Recommendation; Regulation; Reporting; Research; Role; Sampling; Seafood; Selenium; Serum; Smoking; Source; Sports; Subgroup; Sum; Testosterone; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyroxine; Time; Toxicology; Triglycerides; Triiodothyronine; Work; base; cohort; environmental agent; exposed human population; glucose metabolism; hazard; hormone binding protein; hormone metabolism; insight; interest; lipid disorder; lipid metabolism; persistent organic pollutants; pollutant; polybrominated diphenyl ether; preservation; protein transport; secondary analysis; sex; steroid hormone; urinary

7. Project Summary/Abstract Consumption of fish is a major source of exposure to environmental contaminants for the general population, including persistent organic pollutants such as polychlorinated biphenyls (PCBs), p,p’-diphenyldichloroethene (DDE), polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFAS), as well as metals such as methyl mercury (meHg). Exposure to these pollutants may cause dysregulation of endocrine function, affecting steroid and thyroid hormones as well as glucose and lipid metabolism. To date, few studies have evaluated the impact of multiple contaminants found in fish on endocrine function, and even fewer have considered that the harmful effects of contaminants in fish may be counterbalanced by beneficial nutrients such as selenium and iodide. The Great Lakes Fish Consumer Study (GLFCS) is an ongoing longitudinal study of both frequent and infrequent consumers of sport fish. In this population, we have previously demonstrated associations of PCBs, PBDEs, DDE and/or fish consumption with various endocrine endpoints, including increased diabetes incidence and changes in hemoglobin A1c, thyroid hormones, thyroid autoantibodies, steroid hormones and hormone binding proteins. We propose to leverage this unique, well characterized cohort to measure additional contaminant exposures and nutrients, namely PFAS, Hg, and selenium, in banked biosamples from 490 study participants. Specifically, we will (1) determine if key measures of endocrine function in the GLFCS cohort are associated with exposure to PFAS and mercury individually and in mixed exposures with PCBs, DDE and PBDEs; and (2) investigate if levels of serum selenium and urinary iodide impact associations of endocrine function with PFAS, mercury, PCBs, DDE and PBDEs. We will also explore associations of mercury and PFAS on self-reported incident and prevalent endocrine disease, including diabetes, hypothyroidism and hyperlipidemia.Currently available exposure and nutrient measurements include serum PCBs, DDE, and PBDEs, urinary iodide, and estimated mercury intake from reported fish consumption. Currently available outcome measurements include self-reported diabetes, prediabetes, hypothyroidism; thyroid hormones, sex steroid hormones, gonadotropins, hormone binding proteins, autoantibodies and markers of glucose and lipid homeostasis. We will use both standard (linear, logistic and Cox proportional hazards regression models) and alternative (elastic net; propensity score adjustment; weighted quantile sum regression) analytic approaches to evaluate associations of individual chemicals and mixtures of contaminants with markers of endocrine dysregulation. This investigation is expected to lead to a better understanding of the effects of pollutants on endocrine function and disease in adults, which will guide advice to consumers on the risks and benefits of fish consumption.

7.项目总结/摘要 食用鱼类是普通民众接触环境污染物的主要来源， 包括持久性有机污染物，如多氯联苯、p，p '-二苯基二氯乙烯 (DDE)、多溴联苯醚和全氟烷基物质，以及 甲基汞（MeHg）。接触这些污染物可能会导致内分泌功能失调， 影响类固醇和甲状腺激素以及葡萄糖和脂质代谢。迄今为止，很少有研究 评估了鱼类中发现的多种污染物对内分泌功能的影响， 认为污染物对鱼类的有害影响可由有益的营养素抵消 例如硒和碘化物。五大湖鱼类消费者研究是一项正在进行的纵向研究 经常和不经常食用运动鱼类的消费者。在这个群体中，我们之前已经证明了 多氯联苯、多溴联苯醚、DDE和/或鱼类消费与各种内分泌终点的关联， 糖尿病发病率增加和血红蛋白A1 c、甲状腺激素、甲状腺自身抗体的变化， 类固醇激素和激素结合蛋白。我们建议利用这种独特的， 队列测量额外的污染物暴露和营养素，即PFAS，汞和硒， 来自490名研究参与者的库存生物样本。具体而言，我们将（1）确定 GLFCS队列中的内分泌功能与单独暴露于PFAS和汞相关， 混合暴露与多氯联苯，DDE和多溴联苯醚;和（2）调查，如果血清硒和尿 碘影响内分泌功能与PFAS、汞、多氯联苯、DDE和多溴二苯醚的关系。我们还将 探索汞和PFAS与自我报告的事件和流行内分泌疾病的关系， 包括糖尿病、甲状腺功能减退症和高脂血症。 测量包括血清PCB，DDE和PBDEs，尿碘和估计的汞摄入量， 鱼的消费量。目前可用的结果测量包括自我报告的糖尿病， 糖尿病前期，甲状腺功能减退;甲状腺激素，性类固醇激素，促性腺激素，激素结合 蛋白质、自身抗体以及葡萄糖和脂质稳态的标志物。我们将使用两个标准（线性， logistic和考克斯比例风险回归模型）和替代模型（弹性网络;倾向评分 调整;加权分位数和回归）分析方法，以评估个人的关联 具有内分泌失调标志物的化学品和污染物的混合物。这项调查是 预计将导致更好地了解污染物对内分泌功能和疾病的影响， 这将指导消费者关于食用鱼类的风险和益处的建议。