U.S. Environmental Protection Agency, National Center for Environmental Assessment, Research Triangle Park, NC 27711, USA.
Toxicol Appl Pharmacol. 2011 Jul 15;254(2):181-91. doi: 10.1016/j.taap.2010.10.016. Epub 2010 Oct 27.
Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose-response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addresses many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose-response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user-friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance.
传统上，无观察到不良效应水平 (NOAEL) 方法已被用于确定从动物毒理学数据出发的临界点 (POD)，以便用于人类健康风险评估。然而，这种方法存在许多已被明确定义的局限性，例如严格依赖于研究中确定关键效应的剂量选择、剂量间隔和样本量。此外，NOAEL 方法未能考虑剂量反应曲线的形状和其他相关信息。基准剂量 (BMD) 方法最初是在 20 世纪 80 年代作为 NOAEL 方法的替代方法提出的，它解决了 NOAEL 方法的许多局限性。它对剂量选择和间隔的依赖性较小，并考虑了剂量反应曲线的形状。此外，估计 BMD 的 95%下限置信限 (BMDL) 会导致 POD 适当考虑研究质量（即样本量）。随着最近用户友好的 BMD 软件程序的出现，包括美国环境保护署 (U.S. EPA) 的基准剂量软件 (BMDS)，BMD 已成为全球许多健康组织的首选方法。本文讨论了美国环境保护署 (U.S. EPA) 开发的 BMD 方法和相应的软件（即 BMDS 版本 2.1.1），并与最近发布的欧洲食品安全局 (EFSA) BMD 指南进行了比较。
