Elucidating Risks: From Exposure and Mechanism to Outcome

阐明风险：从暴露和机制到结果

• 批准号: 8278549
• 负责人: JAMES A SWENBERG
• 金额: $ 284.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278549
• 关键词: Address; Advisory Committees; Aromatic Polycyclic Hydrocarbons; Basic Science; Bioinformatics; Biological Availability; Biological Markers; Biometry; Bioremediations; Chemicals; Chemistry; Chronic; Collaborations; Communities; Complex; Critical Pathways; Data; Data Analyses; Discipline; Disease; Dose; Engineering; Ensure; Environment; Environmental Engineering technology; Environmental Health; Environmental Pollution; Excision; Experimental Models; Exposure to; Faculty; Fostering; Foundations; Gap Junctions; General Population; Genetic; Genetic Predisposition to Disease; Government Agencies; Halogenated Hydrocarbons; Hazardous Chemicals; Hazardous Waste Sites; Health; Heavy Metals; Human; Individual; Individual Differences; Industry; Interdisciplinary Study; Knowledge; Laboratory Research; Lead; Metabolic Pathway; Methods; Modeling; Molecular; Monitor; Nature; Outcome; Poison; Postdoctoral Fellow; Predisposition; Process; Public Health; Research; Research Personnel; Research Support; Resources; Risk; Risk Assessment; Risk Reduction; Science; Scientific Advances and Accomplishments; Signal Recognition Particle; Site; Solutions; Source; Staging; Students; Superfund; System; Systems Biology; Toxic effect; Training; Translational Research; Uncertainty; Work; analytical tool; base; commercialization; gene environment interaction; genotoxicity; hazard; improved; in vivo; meetings; microbial community; population based; practical application; programs; remediation; response; superfund site; tool

DESCRIPTION (provided by applicant): The UNC-CH Program's multidisciplinary research will address scientific issues that underpin the assessment and reduction of risks to human health associated with high priority chemicals at Superfund sites. The overall specific aims are to improve the scientific foundation for risk assessment, elucidate mechanisms responsible for inter-individual susceptibility, advance approaches to assessing exposure to hazardous chemicals, and more efficiently reduce risks by remediation of hazardous waste sites. In this competing continuation, we will focus on three major classes of chemicals ~ polycyclic aromatic hydrocarbons (PAHs), halogenated hydrocarbons, and heavy metals ~ in three biomedical and two non-biomedical projects, two Research Support Cores, a Research Translation Core (RTC), and an Administrative Core. Research themes that cross multiple projects and cores include: (1) developing biomarkers of exposure and effect for human and experimental models of environmental disease over a range of exposure levels to improve low-dose quantitative risk assessment; (2) applying new molecular tools in a systems biology framework to understand metabolic pathways critical for environmental disease, predict in vivo inter-individual differences in susceptibility and risk, and evaluate complex microbial communities in bioremediation systems; (3) using advanced analytical tools to identify mechanisms of genotoxicity; (4) using advanced statistical and bioinformatics methods to evaluate gene-environment interactions; and (5) quantifying the chronic exposure and bioavailability of toxic compounds in environmental systems. This work will also be integrated by sharing methods and resources across projects and cores, by regular meetings of all researchers, and by co-advising of trainees by faculty in different projects and cores. Working with investigators, the RTC will enhance the capacity of government agencies to provide technical assistance to communities, develop improved decision-support tools, and promote the commercialization of our research products. This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity.

描述（由申请人提供）：UNC-CH 计划的多学科研究将解决支持评估和减少与超级基金地点的高优先级化学品相关的人类健康风险的科学问题。总体具体目标是完善风险评估的科学基础，阐明个体间易感性的机制，推进评估危险化学品暴露的方法，并通过危险废物场地的修复更有效地降低风险。在这个竞争性的延续中，我们将在三个生物医学和两个非生物医学项目、两个研究支持核心、一个研究翻译核心 (RTC) 中重点关注三大类化学品——多环芳烃 (PAH)、卤代烃和重金属。 ）和一个行政核心。跨多个项目和核心的研究主题包括：（1）开发暴露水平的生物标志物和对人类和环境疾病实验模型在一系列暴露水平下的影响，以改进低剂量定量风险评估； （2）在系统生物学框架中应用新的分子工具，了解对环境疾病至关重要的代谢途径，预测体内个体间易感性和风险的差异，并评估生物修复系统中复杂的微生物群落； (3) 使用先进的分析工具来确定遗传毒性机制； （4）利用先进的统计和生物信息学方法评估基因与环境的相互作用； (5) 量化环境系统中有毒化合物的长期暴露和生物利用度。这项工作还将通过跨项目和核心共享方法和资源、所有研究人员的定期会议以及不同项目和核心的教师为学员提供共同建议来整合。 RTC 将与研究人员合作，增强政府机构向社区提供技术援助的能力，开发改进的决策支持工具，并促进我们研究产品的商业化。该计划与超级基金高度相关，解决高优先级化学品问题，重点关注健康影响的机制、暴露评估以及减轻暴露和毒性的补救措施。