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二噁英类化合物哺乳动物相对效力估计值的精确数据库的开发。

Development of a refined database of mammalian relative potency estimates for dioxin-like compounds.

作者信息

Haws Laurie C, Su Steave H, Harris Mark, Devito Michael J, Walker Nigel J, Farland William H, Finley Brent, Birnbaum Linda S

机构信息

ChemRisk, 8024 Mesa Dr., #126, Austin, Texas 78731, USA.

出版信息

Toxicol Sci. 2006 Jan;89(1):4-30. doi: 10.1093/toxsci/kfi294. Epub 2005 Aug 24.

Abstract

The toxic equivalency factor (TEF) approach has been widely accepted as the most feasible method available at present for evaluating potential health risks associated with exposure to mixtures of dioxin-like compounds (DLCs). The current mammalian TEFs for the DLCs were established by the World Health Organization (WHO) following the meeting of an international expert panel in June of 1997. The TEFs recommended by WHO were determined based on a consensus of scientific judgment and were presented as point estimates. However, the relative potency estimates (REPs) underlying the TEFs were derived from a heterogeneous data set and often span several orders of magnitude. In this article, we present a refined database of mammalian REPs that we believe will facilitate better characterization of the variability and uncertainty inherent in the data. The initial step involved reviewing the REP database used by the WHO panel during its review in 1997. A set of criteria was developed to identify REPs that were determined to be the most representative measure of a biological response and of adequate quality for use in quantitative analyses. REPs were determined to be inappropriate for use in quantitative analyses if any of the established exclusion criteria were met. Comparison of data records to the established exclusion criteria resulted in the identification of a substantial number of REPs believed to be inappropriate for use in quantitative analyses. Next, studies published after 1997 were added to the database. The availability of such a refined database will improve risk assessment for this class of compounds by including additional information from new studies and facilitating the use of quantitative approaches in the further development of TEFs.

摘要

毒性当量因子(TEF)方法已被广泛接受,作为目前评估与接触二噁英类化合物(DLCs)混合物相关潜在健康风险的最可行方法。目前用于DLCs的哺乳动物TEFs是世界卫生组织(WHO)在1997年6月召开的国际专家小组会议之后确定的。WHO推荐的TEFs是基于科学判断的共识确定的,并以点估计值呈现。然而,TEFs背后的相对效力估计值(REPs)来自一个异质数据集,通常跨越几个数量级。在本文中,我们提供了一个经过完善的哺乳动物REPs数据库,我们认为这将有助于更好地表征数据中固有的变异性和不确定性。第一步是回顾WHO专家小组在1997年评审期间使用的REP数据库。制定了一套标准,以识别那些被确定为生物反应最具代表性的测量指标且质量足以用于定量分析的REPs。如果符合任何既定的排除标准,则确定该REP不适用于定量分析。将数据记录与既定的排除标准进行比较,结果发现大量REPs被认为不适用于定量分析。接下来,将1997年之后发表的研究添加到数据库中。这样一个经过完善的数据库的可用性将通过纳入新研究的更多信息并促进在TEFs的进一步发展中使用定量方法,来改进对此类化合物的风险评估。

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