Crump K S
ICF Kaiser Engineers, Ruston, Louisiana 71270.
Risk Anal. 1994 Dec;14(6):1033-8. doi: 10.1111/j.1539-6924.1994.tb00073.x.
The utility of mechanistic models of cancer for predicting cancer risks at low doses is examined. Based upon a general approximation to the dose-response that is valid at low doses, it is shown that at low doses the dose-response predicted by a mechanistic model is a linear combination of the dose-responses for each of the physiological parameters in the model that are affected by exposure. This demonstrates that, unless the mechanistic model provides a theoretical basis for determining the dose-responses for these parameters, the extrapolation of risks to low doses using a mechanistic model is basically "curve fitting," just as is the case when extrapolating using statistical models. This suggests that experiments to generate data for use in mechanistic models should emphasize measuring the dose-response for dose-related parameters as accurately as possible and at the lowest feasible doses.
研究了癌症机制模型在预测低剂量癌症风险方面的效用。基于在低剂量下有效的剂量反应一般近似值，结果表明，在低剂量时，机制模型预测的剂量反应是模型中受暴露影响的每个生理参数的剂量反应的线性组合。这表明，除非机制模型为确定这些参数的剂量反应提供理论基础，否则使用机制模型将风险外推至低剂量基本上就是“曲线拟合”，这与使用统计模型进行外推的情况相同。这表明，为生成用于机制模型的数据而进行的实验应强调尽可能准确地在最低可行剂量下测量与剂量相关参数的剂量反应。
