Climate Change Data Portal
DOI | 10.3109/10408444.2013.853726 |
Shape and steepness of toxicological dose-response relationships of continuous endpoints | |
Slob, Wout1; Setzer, R. Woodrow2 | |
发表日期 | 2014-03-01 |
ISSN | 1040-8444 |
卷号 | 44期号:3页码:270-297 |
英文摘要 | A re-analysis of a large number of historical dose-response data for continuous endpoints indicates that an exponential or a Hill model with four parameters adequately describes toxicological dose-responses. No exceptions were found for the datasets considered, which related to a wide variety of endpoints and to both in vivo and in vitro studies of various types. For a given endpoint/study type dose-response shapes were found to be homogenous among chemicals in the in vitro studies considered, while a mild among-chemical variation in the steepness parameter seemed to be present in the in vivo studies. Our findings have various practical consequences. For continuous endpoints, model selection in the BMD approach is not a crucial issue. The often applied approach of using constraints on the model parameters to prevent "infinite" slopes at dose zero in fitting a model is not in line with our findings, and appears to be unjustified. Instead, more realistic ranges of parameter values could be derived from re-analyses of large numbers of historical dose-response datasets in the same endpoint and study type, which could be used as parameter constraints in future individual datasets. This approach will be particularly useful for weak datasets (e.g. few doses, much scatter). In addition, this approach may open the way to use fewer animals in future studies. In the discussion, we argue that distinctions between linear, sub/supralinear or thresholded dose-response shapes, based on visual inspection of plots, are not biologically meaningful nor useful for risk assessment. |
英文关键词 | BMD;dose-response shape;historical data;linearity;model uncertainty;parameter constraints;sublinearity;threshold |
语种 | 英语 |
WOS记录号 | WOS:000331848100003 |
来源期刊 | CRITICAL REVIEWS IN TOXICOLOGY
![]() |
来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/58531 |
作者单位 | 1.Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands; 2.US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA |
推荐引用方式 GB/T 7714 | Slob, Wout,Setzer, R. Woodrow. Shape and steepness of toxicological dose-response relationships of continuous endpoints[J]. 美国环保署,2014,44(3):270-297. |
APA | Slob, Wout,&Setzer, R. Woodrow.(2014).Shape and steepness of toxicological dose-response relationships of continuous endpoints.CRITICAL REVIEWS IN TOXICOLOGY,44(3),270-297. |
MLA | Slob, Wout,et al."Shape and steepness of toxicological dose-response relationships of continuous endpoints".CRITICAL REVIEWS IN TOXICOLOGY 44.3(2014):270-297. |
条目包含的文件 | 条目无相关文件。 |
个性服务 |
推荐该条目 |
保存到收藏夹 |
导出为Endnote文件 |
谷歌学术 |
谷歌学术中相似的文章 |
[Slob, Wout]的文章 |
[Setzer, R. Woodrow]的文章 |
百度学术 |
百度学术中相似的文章 |
[Slob, Wout]的文章 |
[Setzer, R. Woodrow]的文章 |
必应学术 |
必应学术中相似的文章 |
[Slob, Wout]的文章 |
[Setzer, R. Woodrow]的文章 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。