The Influence of Exposure Variability on Dose-Response Relationships

Abstract

A conceptual model is presented which ties together the distributions of exposure, dose, damage, and risk of disease from airborne toxic agents. The input to the model is a series of daily exposures described by a lognormal distribution function. The output is the distribution of risks to a discrete population of uniformly-exposed workers. Two points are made with reference to the influence of exposure variability on the model. First, it is important to differentiate between the variability of air levels associated with a particular job and that associated with individual work practices. Analysis of variance techniques can be used in this context. Second, the importance of exposure variability as a determinant of hazard can be inferred from the particular linkages between the distributions of exposure, dose, and damage for a particular toxicant. When the chemical is slowly eliminated from the target organ, for example, the dose becomes very great relative to the daily input and fluctuations in exposure from day to day are dampened at the site of damage. Both of these points are illustrated for inorganic lead with published exposure data and a toxicokinetic model.