Miller F J, Graham J A
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Toxicol Lett. 1988 Dec;44(3):231-46. doi: 10.1016/0378-4274(88)90162-2.
Knowledge of the quantitative relationship between exposure concentration and delivered dose (i.e., dosimetry) is a fundamental starting point in the evaluation of the toxicity of chemicals, not only for intra- and interspecies comparisons but also for designing experiments that elucidate mechanisms of action and that identify issues or research areas for further study. To these ends a mathematical, lower respiratory tract dosimetry model for gases has been developed which, when linked to experimentally determined upper respiratory tract removal of a gas, can be used for dosimetric extrapolations between one test condition to a theoretical condition (e.g., animal-to-man, child-to-adult, high-to-low dose). This paper, using the ozone (O3) dosimetry model as an example, describes (1) the results of sensitivity analyses that have identified variables that can significantly influence the precision of model predicted doses, (2) research progress in improving the precision of those highly sensitive variables, and (3) approaches being used to validate the model. Results from studies of upper respiratory tract removal of O3 in animals and human are used as inputs into the mathematical model of the lower respiratory tract to illustrate applications of dosimetric extrapolations.
了解暴露浓度与输送剂量之间的定量关系（即剂量测定法）是评估化学物质毒性的基本出发点，这不仅适用于种内和种间比较，还适用于设计阐明作用机制以及确定进一步研究的问题或研究领域的实验。为此，已经开发了一种用于气体的数学下呼吸道剂量测定模型，该模型与通过实验确定的气体在上呼吸道的清除率相关联时，可用于在一种测试条件与理论条件（例如，动物到人、儿童到成人、高剂量到低剂量）之间进行剂量测定推断。本文以臭氧（O₃）剂量测定模型为例，描述了：（1）敏感性分析的结果，这些分析确定了可能显著影响模型预测剂量精度的变量；（2）在提高那些高度敏感变量精度方面的研究进展；（3）用于验证该模型的方法。将动物和人类上呼吸道对O₃清除率的研究结果用作下呼吸道数学模型的输入，以说明剂量测定推断的应用。
