Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.
Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.
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DOI：
10.1002/em.21870
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发表时间：
2014-10
影响因子：
2.8
通讯作者：
White PA
中科院分区：
文献类型：
--
作者：
Johnson GE;Soeteman-Hernández LG;Gollapudi BB;Bodger OG;Dearfield KL;Heflich RH;Hixon JG;Lovell DP;MacGregor JT;Pottenger LH;Thompson CM;Abraham L;Thybaud V;Tanir JY;Zeiger E;van Benthem J;White PA
遗传毒理学数据传统上用于定性而不是定量的危害评估。作为我们分析甲磺酸乙酯（EMS）和甲磺酸甲酯（MMS）剂量反应数据的早期报告的延续（Gollapudi等人，2013年），在这里，我们提出了1-乙基-1-亚硝基脲（ENU）和1-甲基-1-亚硝基脲（MNU）剂量反应数据的分析，以及用于确定遗传毒性出发点（PoD）指标的其他方法。我们之前描述了确定遗传毒性终点的无明显遗传毒性效应水平（NOGEL）、折点剂量（BPD;之前称为Td）和基准剂量（BMD 10）的方法。在本研究中，我们采用这些方法，沿着一种新方法，以确定非线性斜率转换剂量（STD），并采用替代方法确定BPD和BMD，以分析一系列体外和体内终点的9个ENU和22个MNU数据集。对于大多数基因突变和染色体损伤研究，可以轻松计算NOGEL、BMDL 10和BMDL 1 SD PoD指标;但是，由于数据限制和基础统计方法的约束，无法始终推导出BPD和STD。BMDL 10值通常低于其他PoD，BMDL 10值的分布产生最低的PoD中位数。我们的观察结果表明，在本研究中研究的方法中，BMD方法是定量描述遗传毒理学数据的首选PoD。一旦通过这种方法计算出遗传毒理学PoD，它们就可以用来推导出参考剂量和暴露值的范围，这些值可能对评估人类风险和监管决策有用。Environ.摩尔变异体55：609-623，2014.© 2014作者。环境和分子诱变出版的威利期刊，公司。
Genetic toxicology data have traditionally been employed for qualitative, rather than quantitative evaluations of hazard. As a continuation of our earlier report that analyzed ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS) dose–response data (Gollapudi et al., 2013), here we present analyses of 1‐ethyl‐1‐nitrosourea (ENU) and 1‐methyl‐1‐nitrosourea (MNU) dose–response data and additional approaches for the determination of genetic toxicity point‐of‐departure (PoD) metrics. We previously described methods to determine the no‐observed‐genotoxic‐effect‐level (NOGEL), the breakpoint‐dose (BPD; previously named Td), and the benchmark dose (BMD10) for genetic toxicity endpoints. In this study we employed those methods, along with a new approach, to determine the non‐linear slope‐transition‐dose (STD), and alternative methods to determine the BPD and BMD, for the analyses of nine ENU and 22 MNU datasets across a range of in vitro and in vivo endpoints. The NOGEL, BMDL10 and BMDL1SD PoD metrics could be readily calculated for most gene mutation and chromosomal damage studies; however, BPDs and STDs could not always be derived due to data limitations and constraints of the underlying statistical methods. The BMDL10 values were often lower than the other PoDs, and the distribution of BMDL10 values produced the lowest median PoD. Our observations indicate that, among the methods investigated in this study, the BMD approach is the preferred PoD for quantitatively describing genetic toxicology data. Once genetic toxicology PoDs are calculated via this approach, they can be used to derive reference doses and margin of exposure values that may be useful for evaluating human risk and regulatory decision making. Environ. Mol. Mutagen. 55:609–623, 2014. © 2014 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.
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影响因子：
3.3
作者：
通讯作者：
--
DOI：
10.1016/0027-5107(90)90173-2
发表时间：
1990-07-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
BERANEK, DT
通讯作者：
BERANEK, DT
影响因子：
3.8
作者：
CRUMP, KS
通讯作者：
CRUMP, KS
影响因子：
2.8
作者：
Johnson GE;Soeteman-Hernández LG;Gollapudi BB;Bodger OG;Dearfield KL;Heflich RH;Hixon JG;Lovell DP;MacGregor JT;Pottenger LH;Thompson CM;Abraham L;Thybaud V;Tanir JY;Zeiger E;van Benthem J;White PA
通讯作者：
White PA
影响因子：
3.5
作者：
Gocke, Elmar;Wall, Michael
通讯作者：
Wall, Michael