Characterizing dose-response I: Critical assessment of the benchmark dose concept
Characterizing dose-response I: Critical assessment of the benchmark dose concept
复制标题
DOI：
10.1111/j.1539-6924.1998.tb00911.x
复制
发表时间：
1998-02-01
期刊：
影响因子：
3.8
通讯作者：
Morris, RW
中科院分区：
文献类型：
--
作者：
Murrell, JA;Portier, CJ;Morris, RW
我们对Crump（(1)）提出的基准剂量（BMD）方法进行了关键评估，该方法可作为设定毒性风险评估的特征剂量水平的替代方法。未观察到不良反应水平（NOAEL）方法一直受到批评，因为它没有使用所有的数据，因为获得的特征剂量水平取决于剂量水平和研究设计的统计精度（样本量）。根据点估计的置信度界来定义骨密度，得到的特征剂量也随统计精度而变化，仍然取决于研究剂量水平。(2)不加选择地选择基准反应水平可能导致BMD几乎不能反映使用所有数据可获得的剂量-反应行为。另一个值得关注的问题是，定量响应情况下的BMD定义与连续响应情况不同。具体来说，使用增加效应除以背景响应的比率来定义连续数据的骨密度，会导致对所研究终点的自然背景的任意依赖，从而使终点之间的比较变得没有意义，标准变得更加任意。我们将修正基准剂量定义为使用增加效应的比率除以整个不良反应范围的点估计，这使得基准反应水平的放置一致，并提供BMD与剂量-反应曲线形状的关系更加一致。
We present a critical assessment of the benchmark dose (BMD) method introduced by Crump((1)) as an alternative method for setting a characteristic dose level for toxicant risk assessment. The no-observed-adverse-effect-level (NOAEL) method has been criticized because it does not use all of the data and because the characteristic dose level obtained depends on the dose levels and the statistical precision (sample sizes) of the study design. Defining the BMD in terms of a confidence bound on a point estimate results in a characteristic dose that also varies with the statistical precision and still depends on the study dose levels.((2)), Indiscriminate choice of benchmark response level may result in a BMD that reflects little about the dose-response behavior available from using all of the data. Another concern is that the definition of the BMD for the quantal response case is different for the continuous response case. Specifically, defining the BMD for continuous data using a ratio of increased effect divided by the background response results in an arbitrary dependence on the natural background for the endpoint being studied, making comparison among endpoints less meaningful and standards more arbitrary. We define a modified benchmark dose as a point estimate using the ratio of increased effect divided by the full adverse response range which enables consistent placement of the benchmark response level and provides a BMD with a more consistent relationship to the dose-response curve shape.