Leisenring W, Ryan L
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
Regul Toxicol Pharmacol. 1992 Apr;15(2 Pt 1):161-71. doi: 10.1016/0273-2300(92)90047-d.
The use of the no observed adverse effect level (NOAEL) in setting allowable exposure levels for noncancer endpoints is a source of controversy. Based on computer simulations and empirical studies, several authors have criticized the use of the NOAEL in terms of its sensitivity to sample size and its high sampling variability from experiment to experiment. The purpose of this paper is to derive the statistical distribution of the NOAEL. Using Weibull models, we investigate the impact of the shape of the underlying dose-response curve on the distribution of the NOAEL. The results confirm previous criticisms of the NOAEL and show that average risk levels associated with the NOAEL may be substantial. These results provide additional motivation for developing alternative approaches to risk assessment.
在设定非癌症终点的可允许暴露水平时使用未观察到有害作用水平（NOAEL）存在争议。基于计算机模拟和实证研究，一些作者批评了NOAEL在对样本量的敏感性以及不同实验之间高抽样变异性方面的应用。本文的目的是推导NOAEL的统计分布。使用威布尔模型，我们研究了潜在剂量反应曲线的形状对NOAEL分布的影响。结果证实了之前对NOAEL的批评，并表明与NOAEL相关的平均风险水平可能相当大。这些结果为开发替代风险评估方法提供了额外的动力。
