Benzo[a]pyrene Micro-dosing of Humans: A New Tool for Exposure, Risk Assessment and Prevention

人体苯并[a]芘微剂量:暴露、风险评估和预防的新工具

基本信息

  • 批准号:
    10306359
  • 负责人:
  • 金额:
    $ 46.02万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-01-01 至 2023-11-30
  • 项目状态:
    已结题

项目摘要

Polycyclic aromatic hydrocarbons (PAHs), from incomplete combustion of carbon (coal, diesel, auto exhaust, wood smoke, etc.) are 3 of top 10 chemicals of concern for ATSDR. In rodent models, PAHs are potent lung carcinogens and there is ample epidemiological evidence also for humans. Lung cancer is the #1 cause of cancer deaths worldwide (160,000 in U.S. for 2016). Diagnosis occurs in late stages emphasizing the need for prevention. Benzo[a]pyrene (BaP), the most widely-studied PAH lung carcinogen, is a class 1 known human carcinogen (IARC). The current EPA IRIS cancer risk slope factor for BaP (lifetime exposure) is 7 mg/kg/day-1, assuming linearity over orders of magnitude from rodent tumor studies. Collaborating with Lawrence Livermore National Laboratory we can employ ULPC-accelerator mass spectrometry (AMS) to conduct human ADME studies at doses below average daily dietary exposure. Our overarching premise is: for accurate PK analysis and risk assessment humans are the best model for humans. Conducted under an FDA IND, we will perform 3 novel studies with BaP providing a unique dataset for regulatory agencies charged with providing the most accurate risk assessment possible for BaP (PAH) exposure. 1. Determine the impact of dose (50-250 ng) over a range at or below average daily exposure for a non-smoking U.S. adult. Utilizing ULPC interfaced with AMS determine the impact of dose on metabolic profiles (bioactivation and detoxication) in plasma and urine. Working with our long-term collaborators at Pacific Northwest National Laboratory incorporate these data into their PBPK and risk assessment models. 2. Assess the impact of another PAH, phenanthrene, commonly found in environmental PAH mixtures, on the ADME of BaP. What components of ADME are impacted? Is the effect additive, inhibitory or perhaps synergistic? The answer is critical for risk assessment and testing assumptions of the Relative Potency Factor approach to risk assessment for PAH mixtures currently considered by most regulatory agencies. 3. Test the chemoprevention potential of cruciferous vegetables/supplement, effective in preclinical cancer models and human populations, in humans at environmentally relevant exposure levels of BaP. What is the impact and does it involves alterations in absorption, metabolism and/or excretion? This study will, for the first time, determine the efficacy, potency and mechanism of a whole food, compared to a supplement, with respect to chemoprevention in healthy humans exposed to a dietary chemical carcinogen at a defined environmentally relevant dose.
多环芳烃(PAHs),来自不完全燃烧的碳(煤、柴油、汽车)

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.
  • DOI:
    10.3389/fnut.2021.734334
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    5
  • 作者:
    Williams DE
  • 通讯作者:
    Williams DE
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David E Williams其他文献

COVID 19 breakthrough infection risk: a simple physical model describing the dependence on antibody concentration
COVID 19 突破性感染风险:描述抗体浓度依赖性的简单物理模型
  • DOI:
    10.21203/rs.3.rs-1051588/v1
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    David E Williams
  • 通讯作者:
    David E Williams
Vehicle dynamics and personal exposure to black carbon in the vicinity of at-grade pedestrian infrastructure
  • DOI:
    10.25560/24158
  • 发表时间:
    2014-10
  • 期刊:
  • 影响因子:
    0
  • 作者:
    David E Williams
  • 通讯作者:
    David E Williams
Intermetallic compounds as oxygen evolving anodes for metal electrowinning: Electrochemical dealloying and effects of scale in practical electrochemistry
金属电沉积用析氧阳极的金属间化合物:电化学脱合金化及实际电化学中氧化皮的影响
  • DOI:
    10.1016/j.electacta.2023.143681
  • 发表时间:
    2024-01-20
  • 期刊:
  • 影响因子:
    5.600
  • 作者:
    David E Williams
  • 通讯作者:
    David E Williams

David E Williams的其他文献

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{{ truncateString('David E Williams', 18)}}的其他基金

Benzo[a]pyrene Micro-dosing of Humans: A New Tool for Exposure, Risk Assessment and Prevention
人体苯并[a]芘微剂量:暴露、风险评估和预防的新工具
  • 批准号:
    10057385
  • 财政年份:
    2018
  • 资助金额:
    $ 46.02万
  • 项目类别:
The 5th Aquatic Animal Models for Human Disease Conference
第五届人类疾病水生动物模型会议
  • 批准号:
    8006359
  • 财政年份:
    2010
  • 资助金额:
    $ 46.02万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    8056118
  • 财政年份:
    2010
  • 资助金额:
    $ 46.02万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    8552223
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:
Project 1: PAHs in Humans at Environmental Levels Pharmacokinetics, Metabolism a
项目 1:环境水平下人类多环芳烃的药代动力学、代谢和
  • 批准号:
    9058937
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:
PAHs: New Technologies and Emerging Health Risks
PAH:新技术和新出现的健康风险
  • 批准号:
    7918619
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:
PAHs: New Technologies and Emerging Health Risks
PAH:新技术和新出现的健康风险
  • 批准号:
    8056123
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    8884147
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    9066652
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:
PAHs: New Technologies and Emerging Health Risks
PAH:新技术和新出现的健康风险
  • 批准号:
    8884141
  • 财政年份:
    2009
  • 资助金额:
    $ 46.02万
  • 项目类别:

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