Identification of a critical dose level for risk assessment: Developments in benchmark dose analysis of continuous endpoints
Identification of a critical dose level for risk assessment: Developments in benchmark dose analysis of continuous endpoints
复制标题
DOI：
10.1093/toxsci/kfj057
复制
发表时间：
2006-03-01
影响因子：
3.8
通讯作者：
Filipsson, AF
中科院分区：
文献类型：
--
作者：
Sand, S;von Rosen, D;Filipsson, AF
在化学物质的健康风险评价中，推荐用基准剂量（BMD）法代替无明显不良作用水平（NOAEL）法。在这篇文章中，发展BMD分析从连续的实验数据提出。建议的方法将BMD定义为S形剂量-反应关系的斜率在低剂量区变化最大的剂量。该剂量位于对化学品暴露的敏感性可能开始发生显著变化的区域。它示出的响应（定义为相对于响应的幅度或大小的百分比变化）对应于剂量的斜率变化最大的剂量依赖于剂量-响应曲线的几何形状;响应变得更低，因为曲线变得更不对称和阈值样在低剂量区域。在对称情况下，通过Hill函数描述，与临界剂量水平相关的响应变为21%（定义为相对于响应幅度或大小的百分比变化）。根据Gompertz曲线所反映的不对称性和阈值样特征的极限情况，对应于感兴趣剂量的响应变得低至7.3%（定义为相对于响应幅度或大小的百分比变化）。当保守估计BMD时，使用5-10%范围内的响应值可解释与拟定策略相关的不确定性，并且从风险评估的角度来看可能是适当的。本研究还表明，根据建议的程序定义的BMD可以更精确地估计相对于连续数据的其他方法下定义的BMD。
The benchmark dose (BMD) method has been recommended to replace the no-observed-adverse-effect-level (NOAEL) approach in health risk assessment of chemical substances. In the present article, developments in BMD analysis from continuous experimental data are proposed. The suggested approach defines the BMD as the dose at which the slope of the S-shaped dose-response relationship changes the most in the low-dose region. This dose resides in a region where the sensitivity to chemical exposure may start to change noticeably. It is shown that the response (defined as a percent change relative to the magnitude, or size, of response) corresponding to the dose where the slope changes the most depends on the geometrical shape of the dose-response curve; the response becomes lower as the curve becomes more asymmetrical and threshold-like in the low-dose region. Given a symmetrical case, described by the Hill function, the response associated with the critical dose level becomes 21% (defined as a percent change relative to the magnitude, or size, of response). According to a limiting case of asymmetry and threshold-like characteristics, reflected by a Gompertz curve, the response corresponding to the dose of interest becomes as low as 7.3% (defined as a percent change relative to the magnitude, or size, of response). Use of a response in the range of 5-10% when estimating the BMD conservatively accounts for uncertainties associated with the proposed strategy, and may be appropriate in a risk assessment point of view. The present investigation also indicated that a BMD defined according to the suggested procedure may be estimated more precisely relative to BMDs defined under other approaches for continuous data.