QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
批准号:
3252781
负责人:
HERBERT S ROSENKRANZ
金额:
$9.84万
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-08-01 至 1991-07-31
关键词:
Salmonella artificial intelligence bioassay biotransformation cancer risk chemical carcinogen chemical carcinogenesis chemical structure function engine exhaust environment related neoplasm /cancer enzyme induction /repression hamsters laboratory rat mutagen testing neoplastic cell culture for noncancer research nitrogenous heterocyclic compound tissue /cell culture toxicant screening
中文摘要
硝化多环芳烃的生物活性
碳氢化合物(硝基芳烃)是广泛研究的对象
主要是因为它具有很强的致突变性和致癌性
一些硝基芳烃以及它们广泛存在于
环境,主要是不完全燃烧的结果
流程。然而,我们大多数人并不是主要接触到
单独的化合物,而是复杂的混合物
户外(汽车、发电厂等排放的废气)和
室内(香烟烟雾、暖气、炉子、烤箱等)。这个
本申请中提出的工作的目标是将
不同硝基芳烃类化合物的遗传毒性和致癌活性
排放的人工混合物和萃取物的活性
颗粒物,以便使用单一化学品的数据来评估
暴露在复杂混合物中的风险。拟议的项目,
它使用了计算机化和试验性的
方法论,将包括具有以下专业知识的专业人员
化学、生物化学、微生物学、人工智能和
风险评估,并具有丰富的研究经验
硝基芳烃。将使用两种计算机化技术。第一,
计算机自动结构评估(CASE),一种人工
一个智能程序,它是为了预测
硝基芳烃的致突变性,将用于鉴定结构
致突变、遗传毒性和致癌性的决定因素。
二、致癌性预测与电池选型
(CPBS)方法将用于确定适当的电池
筛选单个硝基芳烃和混合物的短期试验
并预测潜在的致癌性,包括致癌性
威力。实验研究将针对评估
混合物中化合物的活性。人工合成的混合物
对硝基芳烃或相关化合物,以及
燃烧排放与个别化学品相结合,将是
检测其致突变性、代谢活性和失活
致突变性、哺乳动物遗传毒性和代谢
生物转化。将解决三个问题:
活动是累加的或受竞争的影响
酶激活,是否确定失活结构
通过案例代表替代的生物改造或竞争
以及复杂混合物的存在如何影响
个体的代谢、致突变性和遗传毒性
化学制品。解决关于外推法的几个问题
从单个组分到混合物将允许数据
与生物利用度、新陈代谢、
遗传毒性、解毒和排泄用于减少
年人体暴露风险评估中的不确定性
不完全燃烧产物和其他复杂混合物。
英文摘要
The biological activity of nitrated polycyclic aromatic
hydrocarbons (nitroarenes) has ben the subject of extensive study
primarily because of the potent mutagenicity and carcinogenicity
of some nitroarenes as well as their widespread occurrence in the
environment, principally as the result of incomplete combustion
processes. However, most of us are not exposed primarily to
individual compounds but rather to complex mixtures both
outdoors (emissions from automobiles, power plants, etc.) and
indoors (cigarette smoke, heaters, stoves, ovens etc). The
objective of the work proposed in this application is to relate the
genotoxic and carcinogenic activities of individual nitroarenes to
activities of artificial mixtures and extracts of emission
particulates in order to use data for single chemicals to evaluate
the risk of exposure to complex mixtures. The proposed project,
which employs both computerized and experimental
methodologies, will involve professionals with expertise in
chemistry, biochemistry, microbiology, artificial intelligence and
risk assessment, and with extensive experience in the study of
nitroarenes. Two computerized techniques will be used. First,
Computer Automated Structure Evaluation (CASE), an artificial
intelligence program which was developed to predict the
mutagenicity of nitroarenes, will be used to identify structural
determinants of mutagenicity, genotoxicity and carcinogenicity.
Second, the Carcinogenicity Prediction and Battery Selection
(CPBS) method will used to identify appropriate batteries of
short-term tests for screening individual nitroarenes and mixtures
and to predict potential carcinogenicity, including carcinogenic
potency. Experimental studies will be directed towards assessing
the activities of compounds in mixtures. Artificial mixtures of
pairs of nitroarenes or related compounds, as well as extracts of
combustion emissions combined with individual chemicals, will be
tested for mutagenicity, metabolic activation and deactivation of
mutagenicity, mammalian genotoxicity and metabolic
biotransformation. Three issues will be addressed: whether
activities are additive or are influenced by competition for
enzymatic activation, whether inactivating structures identified
by CASE represent alternative biotransformation or competition
and how the presence of a complex mixture influences the
metabolism, mutagenicity and genotoxicity of individual
chemicals. Resolving these questions about the extrapolation
from individual components to mixtures would allow data for
individual chemicals concerning bioavailability, metabolism,
genotoxicity, detoxification and excretion to be used to reduce
uncertainty in the assessment of human risk from exposure in
incomplete combustion products and other complex mixtures.
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会议论文
TRAINING IN COMPUTATIONAL TOXICOLOGY
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批准号:6604002
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项目类别:
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资助金额:$9.02万
-
财政年份:2000
-
负责人:HERBERT S ROSENKRANZ
-
依托单位:
TRAINING IN COMPUTATIONAL TOXICOLOGY
-
批准号:6498263
-
项目类别:
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资助金额:$8.42万
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财政年份:2000
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负责人:HERBERT S ROSENKRANZ
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依托单位:
TRAINING IN COMPUTATIONAL TOXICOLOGY
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批准号:6080877
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项目类别:
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资助金额:$3.48万
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财政年份:2000
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负责人:HERBERT S ROSENKRANZ
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依托单位:
TRAINING IN COMPUTATIONAL TOXICOLOGY
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批准号:6350804
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项目类别:
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资助金额:$7.25万
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财政年份:2000
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负责人:HERBERT S ROSENKRANZ
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依托单位:
QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
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批准号:3252787
-
项目类别:
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资助金额:$9.4万
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财政年份:1990
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负责人:HERBERT S ROSENKRANZ
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依托单位:
QUANTIFYING NITROARENE GENOTOXICITY IN COMPLEX MIXTURES
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批准号:3252785
-
项目类别:
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资助金额:$9.69万
-
财政年份:1988
-
负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL BIOLOGY
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批准号:3536086
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项目类别:
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资助金额:$10.29万
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财政年份:1978
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3820992
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3939067
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3812824
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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:HERBERT S ROSENKRANZ
-
依托单位:
ENVIRONMENTAL CARCINOGENESIS
-
批准号:3817018
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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:HERBERT S ROSENKRANZ
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依托单位:
海外基金