کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5857510 1132011 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An empirical comparison of low-dose extrapolation from points of departure (PoD) compared to extrapolations based upon methods that account for model uncertainty
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
An empirical comparison of low-dose extrapolation from points of departure (PoD) compared to extrapolations based upon methods that account for model uncertainty
چکیده انگلیسی
Experiments with relatively high doses are often used to predict risks at appreciably lower doses. A point of departure (PoD) can be calculated as the dose associated with a specified moderate response level that is often in the range of experimental doses considered. A linear extrapolation to lower doses often follows. An alternative to the PoD method is to develop a model that accounts for the model uncertainty in the dose-response relationship and to use this model to estimate the risk at low doses. Two such approaches that account for model uncertainty are model averaging (MA) and semi-parametric methods. We use these methods, along with the PoD approach in the context of a large animal (40,000+ animal) bioassay that exhibited sub-linearity. When models are fit to high dose data and risks at low doses are predicted, the methods that account for model uncertainty produce dose estimates associated with an excess risk that are closer to the observed risk than the PoD linearization. This comparison provides empirical support to accompany previous simulation studies that suggest methods that incorporate model uncertainty provide viable, and arguably preferred, alternatives to linear extrapolation from a PoD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 67, Issue 1, October 2013, Pages 75-82
نویسندگان
, ,