Benchmark dose calculation from epidemiological data
Benchmark dose calculation from epidemiological data
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DOI：
10.1111/j.0006-341x.2001.00698.x
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发表时间：
2001-09-01
期刊：
影响因子：
1.9
通讯作者：
Grandjean, P
中科院分区：
文献类型：
--
作者：
Budtz-Jorgensen, E;Keiding, N;Grandjean, P
剂量依赖性毒性的阈值对于标准制定至关重要，但可能无法从经验研究中具体说明。相反，Crump（1984）建议计算基准剂量的统计置信下限，他将基准剂量定义为导致小的超额风险的剂量。这一概念有几个优点，并已被监管机构采用，以确定汞等有毒物质的安全接触限值。我们已经研究了这种方法的有效性，适用于与汞暴露相关的连续响应数据的流行病学研究。对于参数线性的模型，我们推导出基准剂量置信下限的近似表达式。我们发现，基准计算是高度依赖于剂量效应函数的选择和基准剂量的定义。因此，我们建议使用几组生物学相关的默认设置来说明对基准结果的影响，并刺激研究，指导先验选择适当的默认设置。
A threshold for dose-dependent toxicity is crucial for standards setting but may not be possible to specify from empirical studies. Crump (1984) instead proposed calculating the lower statistical confidence bound of the benchmark dose, which he defined as the dose that causes a small excess risk. This concept has several advantages and has been adopted by regulatory agencies for establishing safe exposure limits for toxic substances such as mercury. We have examined the validity of this method as applied to an epidemiological study of continuous response data associated with mercury exposure. For models that are linear in the parameters, we derived an approximative expression for the lower confidence bound of the benchmark dose. We find that the benchmark calculations are highly dependent on the choice of the dose effect function and the definition of the benchmark dose. We therefore recommend that several sets of biologically relevant default settings be used to illustrate the effect on the benchmark results and to stimulate research that will guide an a priori choice of proper default settings.