Development of edible sorbent therapies to mitigate dietary exposures to per- and polyfluoroalkyl substances (PFAS)

开发可食用吸附剂疗法以减少膳食中全氟烷基物质和多氟烷基物质 (PFAS) 的暴露

基本信息

批准号：
10590799
负责人：
Meichen Wang
金额：
$ 8.74万
依托单位：
TEXAS A&M AGRILIFE RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-10 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10590799
关键词：
Adsorption Affinity Amendment Animals Benign Binding Biochemistry Biological Assay Biological Availability Birth Weight Blood Blood specimen Body Weight Cell model Cells Chemicals Chemistry Clinical Communities Complement Complex Consumption Data Development Diet Dose Drug Metabolic Detoxication Emergency Situation Environment Environmental Pollutants Event Exposure to Female Fire - disasters Floods Food Food Contamination Frequencies Frontline worker Gastrointestinal tract structure Goals Half-Life Health Human Human Milk Hurricane In Vitro Industrialization Infant Infertility Ingestion Inhalation Exposure Intervention Intestines Kinetics Legal patent Licensing Low Birth Weight Infant Malignant neoplasm of testis Mammalian Cell Methods Microbe Micronutrients Modeling Montmorillonite Mycotoxins Nutrient Oral Organ Organism Outcome Partner in relationship Pathway interactions Phase Poly-fluoroalkyl substances Population Prevalence Process Rattus Reaction Renal carcinoma Reporting Research Safety Site Soil Stomach Surface System Testing Therapeutic Thermodynamics Time Toxic effect Urine Vulnerable Populations Water Work clay comparative efficacy computational chemistry computer studies contaminated drinking water data-driven model dietary dosimetry drinking water efficacy validation environmental chemical exposed human population exposure route first responder immunotoxicity in silico in vitro Assay in vivo in vivo evaluation male molecular dynamics novel pregnant remediation safety study screening simulation skills substance use uptake

Adsorption Affinity Amendment Animals Benign Binding Biochemistry Biological Assay Biological Availability Birth Weight Blood Blood specimen Body Weight Cell model Cells Chemicals Chemistry Clinical Communities Complement Complex Consumption Data Development Diet Dose Drug Metabolic Detoxication Emergency Situation Environment Environmental Pollutants Event Exposure to Female Fire - disasters Floods Food Food Contamination Frequencies Frontline worker Gastrointestinal tract structure Goals Half-Life Health Human Human Milk Hurricane In Vitro Industrialization Infant Infertility Ingestion Inhalation Exposure Intervention Intestines Kinetics Legal patent Licensing Low Birth Weight Infant Malignant neoplasm of testis Mammalian Cell Methods Microbe Micronutrients Modeling Montmorillonite Mycotoxins Nutrient Oral Organ Organism Outcome Partner in relationship Pathway interactions Phase Poly-fluoroalkyl substances Population Prevalence Process Rattus Reaction Renal carcinoma Reporting Research Safety Site Soil Stomach Surface System Testing Therapeutic Thermodynamics Time Toxic effect Urine Vulnerable Populations Water Work clay comparative efficacy computational chemistry computer studies contaminated drinking water data-driven model dietary dosimetry drinking water efficacy validation environmental chemical exposed human population exposure route first responder immunotoxicity in silico in vitro Assay in vivo in vivo evaluation male molecular dynamics novel pregnant remediation safety study screening simulation skills substance use uptake

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项目摘要

ABSTRACT Per- and polyfluoroalkyl substances (PFAS), also known as “forever chemicals”, are emerging contaminants of concern due to their prevalence (in 99% of blood samples in the U.S.), long half-life, and adverse health effects in humans. PFAS can be released, mobilized, and redistributed in the environment during emergencies such as fires, industrial incidents, hurricanes, and flooding, thus enhancing human exposures and health effects. A major challenge associated with these emergencies is protecting vulnerable populations including first responders, frontline personnel, and communities at the impacted sites. There is a critical need for the development of practical strategies to minimize dietary exposures to PFAS from drinking water and food, which account for 90% of human exposures. Mitigation strategies using edible sorbents in the diet are safe for human consumption. The long-term goal is to establish therapeutic sorbent interventions that will reduce oral and inhalation exposures to complex environmental contaminants and microbes. The overall objective of this project is to develop edible, multicomponent sorbents that will effectively reduce PFAS exposures from the diet. In this project, six representative PFAS and their mixtures have been selected for complementary in vitro, in silico, and in vivo studies. In Aim 1, multicomponent sorbents including processed and nutrient-amended clays will be derived from materials that are naturally occurring, or generally recognized as safe. The in vitro adsorption studies will be conducted in simulated gastrointestinal tract models to characterize surface interactions. The detoxification efficacy of sorbent treatment will be validated in mammalian cell models and a living organism (Hydra vulgaris). In Aim 2, molecular dynamics (MD) simulations, energetic analysis, minimalistic MD simulations, and data-driven models will be used to study complex systems containing mixtures of PFAS and multicomponent sorbents. Computational studies will validate sorption mechanisms and thermodynamics and integrate with Aim 1 for sorbent selection and characterization. In Aim 3, the efficacy and safety of selected sorbents will be tested in vivo. Male and pregnant female rats will be exposed to PFAS and sorbents will be included in the diet at varying doses for 3 weeks. The 3 sorbents that most effectively reduce the PFAS bioavailability and show no interference with nutrients will be included in a 6-month safety study. Parameters to be determined include 1) PFAS bioavailability in blood, urine, and breast milk, 2) nutrient levels, 3) body weight, relative organ-to-body weight, and infant birth weight, 4) feed conversion efficiency, and 5) clinical blood biochemistry. It is expected that therapeutic sorbents developed in this research will be field-practical and easily delivered orally to neutralize PFAS mixtures from dietary exposures to protect and treat vulnerable populations during emergencies.

抽象的每种和多氟烷基物质（PFA），也称为“永远的化学物质”，是新兴的污染物由于其患病率（在美国99％的血液样本中），长期生活和不良健康影响引起的关注在人类中。 PFA可以在紧急情况下在环境中释放，动员和重新分布火灾，工业事件，飓风和洪水，从而增强了人类的暴露和健康影响。专业与这些紧急情况相关的挑战是保护包括第一响应者在内的脆弱人群，一线人员和受影响地点的社区。迫切需要开发从饮用水和食物中最大程度地减少对PFA的饮食暴露的实用策略，占90％人类暴露。在饮食中使用可食用排序素的缓解策略可用于人类消费。这长期目标是建立治疗性吸附干预措施，以减少口服和吸入暴露于复杂的环境污染物和微生物。该项目的总体目的是开发可食用，将有效地减少饮食中PFA的多组分吸附剂。在这个项目中，六个已经选择了代表性的PFA及其混合物在体外，在体内和体内选择研究。在AIM 1中，包括加工和养分的粘土在内的多组分吸附剂将源自天然存在或通常被认为是安全的材料。体外吸附研究将是在模拟的胃肠道模型中进行表征表面相互作用。排毒吸附剂治疗的功效将在哺乳动物细胞模型和活生物体（Hydra vulgaris）中得到验证。在AIM 2中，分子动力学（MD）模拟，能量分析，简约MD模拟和数据驱动模型将用于研究包含PFA和多组分吸附剂混合的复杂系统。计算研究将验证焊接机制和热力学，并与AIM 1集成吸附剂的选择和表征。在AIM 3中，将测试选定吸附剂的效率和安全性体内。雄性和怀孕的雌性大鼠将暴露于PFA，吸附剂将在饮食中包括在不同的情况下剂量3周。最有效地降低PFA的生物利用度并且没有任何干扰的3个吸附剂营养素将包括在6个月的安全研究中。要确定的参数包括1）PFA 血液，尿液和母乳中的生物利用度，2）营养水平，3）体重，相对器官对体重，和婴儿的出生体重，4）饲料转化效率和5）临床血液生物化学。预计在这项研究中开发的治疗吸附剂将是现场实行的，并且很容易口服以中和饮食中的PFA混合物在紧急情况下保护和治疗脆弱人群。