Research needs and advances in inhalation dosimetry identified through the use of mathematical dosimetry models of ozone.

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.