TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS
TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS
批准号:
2574468
负责人:
RONALD L MELNICK
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
该项目旨在表征剂量参数,
分布、代谢和消除异生物质。 这
信息可以帮助设计和解释毒理学
加强低剂量外推的科学基础
对人类有风险。 此外,生物现实主义生物数学
模型提供了一个严格的结构,以制定和测试假设,
环境危害的作用机制。 毒代动力学模型可以
还应适应不同的接触途径和剂量方案,
能够适应导致个体间差异的因素。
在上一财年,已创建毒代动力学模型,或
部分开发用于国家正在研究的近20种化学品
毒理学计划(NTP)。 一个更深入的基于生理学的
构建了摄取、代谢和
清除1,3-丁二烯(BD)及其主要代谢产物,
1,2-环氧-3-丁烯(EB)。 这个模型显示,
EB的剂量测定不足以说明
暴露于BD的大鼠和小鼠之间的肿瘤反应。 最近的模型
展示了更大的解剖现实主义和更全面的需求,
涉及的酶学和辅因子变化的表征
在生物转化过程中。
英文摘要
This project is designed to characterize parameters of dose,
distribution, metabolism, and elimination of xenobiotic materials. This
information can aid in the design and interpretation of toxicology
studies and to strengthen the scientific basis for low-dose extrapolation
of risk to humans. Furthermore, biologically realistic biomathematical
models provide a rigorous structure to formulate and test hypotheses on
mechanisms of action of environmental hazards. Toxicokinetic models can
also be adapted to different routes of exposure and dosage regimens and
can accommodate factors that contribute to interindividual variabilities.
During the past fiscal year, toxicokinetic models have been created or
partially developed for nearly 20 chemicals under study by the National
Toxicology Program (NTP). A more in-depth physiologically-based
toxicokinetic model was constructed for the uptake, metabolism, and
clearance of 1,3-butadiene (BD) and its principal metabolite,
1,2-epoxy-3-butene (EB). This model showed that differences in tissue
dosimetry of EB are not sufficiently large to account for differences in
tumor response between rats and mice exposed to BD. Recent models
demonstrate the need for greater anatomical realism and fuller
characterization of the enzymology and cofactor changes that are involved
in the biotransformation processes.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
MECHANISTIC STUDIES ON 1,3-BUTADIENE AND RELATED EPOXIDE-FORMING CHEMICALS
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批准号:6106803
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS
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批准号:6290095
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
MECHANISTIC STUDIES ON 1,3-BUTADIENE AND RELATED EPOXIDE-FORMING CHEMICALS
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批准号:6432435
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS
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批准号:6106800
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
MECHANISTIC STUDIES ON 1,3-BUTADIENE AND RELATED EPOXIDE-FORMING CHEMICALS
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批准号:6290098
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
MECHANISM-BASED MODELING OF ALPHA-2U-GLOBULIN ACCUMULATION IN MALE RAT KIDNEY
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批准号:6106804
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS
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批准号:6432433
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS
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批准号:5202293
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
MECHANISM-BASED MODELING OF ALPHA-2U-GLOBULIN ACCUMULATION IN MALE RAT KIDNEY
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批准号:6290099
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:RONALD L MELNICK
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依托单位:
海外基金