关键词： AGD BMDL DBP Dibutyl phthalate GD IRIS Integrated Risk Information System LOAEL LOEL MOA NOAEL NOEL NRC NTP National Research Council National Toxicology Program OECD Organisation of Economic Co-operation and Development PND POD RACB RT-PCR RfD Risk assessment T Toxicogenomic U.S. EPA U.S. Environmental Protection Agency WOE anogenital distance benchmark dose lower confidence limit dibutyl phthalate gestation day lowest-observed-adverse-effect level lowest-observed-effect level mode of action no-observed-adverse-effect level no-observed-effect level point of departure postnatal day reference dose reproductive assessment by continuous breeding reverse transcriptase polymerase chain reaction testosterone weight of evidence

Mesh ： Animals Dibutyl Phthalate / toxicity Environmental Pollutants / toxicity Genitalia, Male / drug effects growth & development pathology Genomics Male Plasticizers / toxicity Rats Reproduction / drug effects Risk Assessment

来  源：   DOI：10.1016/j.taap.2010.09.006   PDF(Sci-hub)

Abstract：
A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data.
摘要：
进行了一个案例研究，使用邻苯二甲酸二丁酯（DBP），探索一种在风险评估中使用毒物基因组数据的方法。与DBP相关的男性生殖发育结果相关的毒性和毒性基因组数据集被共同考虑，以获取有关作用模式和机制的信息。在这份手稿中,我们描述了DBP毒理学数据库的案例研究评估，重点识别男性生殖发育的全谱效应。对数据进行了评估，以1）评估低剂量和低发生率的发现，以及2）在没有完善的作用方式（MOA）的情况下确定男性生殖毒性终点。这些努力导致了在风险评估背景下对毒性和毒性基因组学研究的数据空白和研究需求的表征。Further,在毒性数据集中识别具有无法解释的MOA的终点对于随后评估毒性基因组数据集评估可以提供的机制信息很有用.在MOA背景下对毒理学数据集的广泛分析为DBP提供了信息资源，以尝试假设MOA（对于没有完善的MOA的终点），并将毒理学基因组和其他机理数据表型锚定到毒性终点和可用的毒理学数据。本案例研究是为风险评估开发毒理学数据源所采取的步骤的一个例子。无论是在一般情况下，特别是包括毒物基因组数据的风险评估。
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