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: 9980906
• 负责人: Mary Ellen Turyk
• 金额: $ 19.16万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980906
• 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; 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。项目摘要/摘要 鱼类食用是普通人群暴露于环境污染物的主要来源， 包括持续的有机污染物，例如多氯联苯（PCB），P，P’-二苯基氯乙烯 （DDE），多溴二苯基醚（PBDES）和全氟烷基物质（PFA）以及类似的金属 作为甲基汞（MEHG）。暴露于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恐怖，以及葡萄糖和脂质代谢。迄今为止，很少有研究 评估了在鱼类中发现的多种污染物对内分泌功能的影响，甚至更少 认为污染物在鱼类中的有害作用可能与有益的营养相抵消 例如硒和碘化物。大湖鱼类消费者研究（GLFC）是一项持续的纵向研究 经常和不经常的运动鱼消费者。在这个人群中，我们以前已经证明 PCB，PBDE，DDE和/或鱼类消耗与各种内分泌终点的关联，包括 糖尿病发病率增加和血红蛋白A1c，甲状腺恐怖，甲状腺自身抗体的变化， 类固醇激素和马酮结合蛋白。我们建议利用这种独特的，良好的特征 在测量其他污染物的暴露和营养的队列，即PFA，HG和硒中 来自490名研究参与者的生物样本。具体来说，我们将（1）确定是否采取关键措施 GLFCS队列中的内分泌功能与PFA和汞的暴露有关 与PCB，DDE和PBDE的混合曝光； （2）研究血清硒和尿液水平是否 内分泌功能与PFA，汞，PCB，DDE和PBDE的碘化物影响关联。我们也会 探索有关自我报告事件和普遍内分泌疾病的汞和PFA的关联， 包括糖尿病，甲状腺功能减退症和高脂血症。目前可用的暴露和养分 测量包括血清PCB，DDE和PBDE，尿碘以及估计的汞摄入量 报告的鱼类消耗。目前可用的结果测量包括自我报告的糖尿病， 前糖尿病，甲状腺功能减退症；甲状腺激素，性类固醇激素，促性腺激素，马酮绑定 蛋白质，自身抗体以及葡萄糖和脂质稳态的标记。我们将同时使用标准（线性， 逻辑和COX比例危害回归模型）和替代性（弹性网；承诺得分 调整;加权分位数总和回归）分析方法来评估个体的关联 污染物与内分泌失调标志物的化学和混合物。这项投资是 预计将更好地了解污染物对内分泌功能和疾病的影响 成年人，这将指导消费者有关鱼类消费的风险和益处的建议。