Allen B, Gentry R, Shipp A, Van Landingham C
The K. S. Crump Group, Inc., ICF Kaiser, 602 East Georgia, Ruston, Louisiana 71270, USA.
Regul Toxicol Pharmacol. 1998 Aug;28(1):38-44. doi: 10.1006/rtph.1998.1226.
Reproductive, including developmental, toxicity risk assessment has typically relied on estimation of toxicity criteria values derived from no-observed-adverse-effect levels (NOAELs). The benchmark dose (BMD) approach has been proposed as an alternative that avoids problems with NOAELs. In this analysis of the reproductive and developmental toxicity observed in a multigeneration study of rats exposed to isopropanol, the BMD approach has been applied to all effects exhibiting significant dose-response relationships. The BMD estimates were very consistent across models and across end points; they were within the range of doses (100 to 500 mg/kg/day) that has been suggested as being the NOAEL. The use of the BMD approach for analysis of isopropanol reproductive toxicity is shown to avoid the experiment-specific argument of whether a particular treatment has induced statistically significant differences, compared to controls, in favor of the estimation of experiment-independent doses corresponding to risk levels of interest. The consistency of the BMD estimates, with values of about 420 mg/kg/day, suggests that, for isopropanol, the available multigeneration study data may provide a suitable basis for considering safe exposure.
生殖毒性（包括发育毒性）风险评估通常依赖于从未观察到不良反应水平（NOAEL）得出的毒性标准值估计。基准剂量（BMD）方法已被提议作为一种避免NOAEL相关问题的替代方法。在对暴露于异丙醇的大鼠进行的多代研究中观察到的生殖和发育毒性分析中，BMD方法已应用于所有呈现显著剂量反应关系的效应。BMD估计值在不同模型和不同终点之间非常一致；它们处于被认为是NOAEL的剂量范围内（100至500毫克/千克/天）。与对照组相比，使用BMD方法分析异丙醇生殖毒性可避免关于特定处理是否诱导了统计学上显著差异的特定实验争议，而倾向于估计与感兴趣的风险水平相对应的与实验无关的剂量。BMD估计值约为420毫克/千克/天，其一致性表明，对于异丙醇而言，现有的多代研究数据可能为考虑安全暴露提供合适的基础。
