Kimmel C A, Gaylor D W
Reproductive Effects Assessment Group, U.S. Environmental Protection Agency, Washington, DC 20460.
Risk Anal. 1988 Mar;8(1):15-20. doi: 10.1111/j.1539-6924.1988.tb01149.x.
The qualitative and quantitative evaluation of risk in developmental toxicology has been discussed in several recent publications. A number of issues still are to be resolved in this area. The qualitative evaluation and interpretation of end points in developmental toxicology depends on an understanding of the biological events leading to the end points observed, the relationships among end points, and their relationship to dose and to maternal toxicity. The interpretation of these end points is also affected by the statistical power of the experiments used for detecting the various end points observed. The quantitative risk assessment attempts to estimate human risk for developmental toxicity as a function of dose. The current approach is to apply safety (uncertainty) factors to the no observed effect level (NOEL). An alternative presented and discussed here is to model the experimental data and apply a safety factor to an estimated risk level to achieve an "acceptable" level of risk. In cases where the dose-response curves upward, this approach provides a conservative estimate of risk. This procedure does not preclude the existence of a threshold dose. More research is needed to develop appropriate dose-response models that can provide better estimates for low-dose extrapolation of developmental effects.
发育毒理学中风险的定性和定量评估在最近的几篇出版物中已有讨论。该领域仍有一些问题有待解决。发育毒理学终点的定性评估和解释取决于对导致所观察到终点的生物学事件、终点之间的关系以及它们与剂量和母体毒性的关系的理解。这些终点的解释还受到用于检测所观察到的各种终点的实验的统计效力的影响。定量风险评估试图根据剂量来估计发育毒性对人类的风险。目前的方法是将安全（不确定）系数应用于未观察到效应水平（NOEL）。这里提出并讨论的另一种方法是对实验数据进行建模，并将安全系数应用于估计的风险水平，以达到“可接受”的风险水平。在剂量反应曲线上升的情况下，这种方法提供了保守的风险估计。该程序并不排除阈剂量的存在。需要开展更多研究来开发合适的剂量反应模型，以便能更好地估计发育效应的低剂量外推情况。
