Kimmel C A
Reproductive and Developmental Toxicology Branch, U.S. Environmental Protection Agency, Washington, DC 20460.
Neurotoxicology. 1990 Summer;11(2):189-98.
The estimation of risk for health effects due to chemical exposure is important to the development of standards for regulating the manufacture, use and release of chemicals into the environment. The quantitative data used to develop risk estimates usually come from laboratory animal studies employing relatively high dose levels. Thus, both interpolation from high to low dose levels and extrapolation from laboratory animals to humans are required. The approach most widely used for noncancer end points is to determine the no-observed-adverse-effect level (NOAEL) for the critical effect and then apply uncertainty factors (UFs) to account for scientific uncertainties in the total data base, such as response variability within and between species, the lack of chronic exposure data, the lack of a NOAEL, etc. The resulting value is a reference dose (RfD), i.e., the dose at or below which there is unlikely to be any excess risk. One difficulty with the NOAEL/UF approach is that it does not provide a basis for estimating risk at doses above the RfD; thus, if the exposure assessment indicates that human exposure is above the RfD, there is no way to judge the risk of that exposure. Alternative quantitative approaches for risk estimation of noncancer end points have been proposed and include both statistical and biologically-based dose-response modeling. Research is currently underway to further develop and explore the application of such approaches.
评估化学物质暴露对健康造成影响的风险，对于制定规范化学物质生产、使用及向环境中释放的标准而言至关重要。用于制定风险评估的定量数据通常来自采用相对高剂量水平的实验动物研究。因此，需要从高剂量水平向低剂量水平进行内插，以及从实验动物向人类进行外推。对于非癌症终点，最广泛使用的方法是确定关键效应的未观察到有害作用水平（NOAEL），然后应用不确定系数（UFs）来考虑整个数据库中的科学不确定性，例如物种内部和物种之间的反应变异性、缺乏慢性暴露数据、缺乏NOAEL等。所得值为参考剂量（RfD），即低于该剂量时不太可能存在任何额外风险。NOAEL/UF方法的一个难点在于，它没有为估计高于RfD的剂量下的风险提供依据；因此，如果暴露评估表明人类暴露高于RfD，则无法判断该暴露的风险。已提出了用于非癌症终点风险评估的替代定量方法，包括基于统计和基于生物学的剂量反应建模。目前正在开展研究以进一步开发和探索此类方法的应用。
