Role of the standard deviation in the estimation of benchmark doses with continuous data
Role of the standard deviation in the estimation of benchmark doses with continuous data
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DOI：
10.1111/j.0272-4332.2004.559_1.x
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发表时间：
2004-12-01
期刊：
影响因子：
3.8
通讯作者：
Slikker, W
中科院分区：
文献类型：
--
作者：
Gaylor, DW;Slikker, W
对于连续数据，风险在这里定义为值高于大百分位数（例如第 99 个百分位数或低于第 1 个百分位数）的动物比例，用于对照动物之间的值分布。众所周知，通过改进的实验技术减少测量的标准偏差将导致基准剂量的置信下限的不太严格（更高）的剂量，估计会产生生物效应异常水平的动物的特定风险。因此，获得稍大（不太严格）的置信下限，可用作低剂量风险评估的出发点。本文表明，除了动物内部测量误差的标准偏差 s(m) 之外，基准剂量主要基于动物之间的标准偏差 s(a) 也很重要。如果基准剂量不正确地基于动物平均值之间的总体标准偏差（包括测量误差变化），则基准剂量将被高估，风险将被低估。偏差随着 s(m) 的增加而增加，相对于 s(a) 的增加。如果 s(m) 小于 s(a) 的三分之一（这是大多数实验设计中实现的条件），则偏差相对较小。
For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m), increases relative to s(a). The bias is relatively small if s(m), is less than one-third of s(a), a condition achieved in most experimental designs.