"INTRODUCTION From the time of Orfila (who first established a relationship between dose and effect)@ acute effects of toxins have been related to the dose administered by ingestion@ by injection@ and more recently@ by skin absorption. With the advent of inhalation experiments@ however@ the concept of ""dose"" (or the amount of material in the body- the body burden) became nebulus as there was no simple relationship between dose and exposure parameters. Consequently@ effects of experimental inhalation exposures have been related to concentration and to exposure duration instead of to body burden or dose. If quantitative information is available on excretion of the material administered (or on one of metabolites)@ that data can often be described by an empirical equation which can then be used to calculate a value proportional to the total body burden.(1@2@3). The main difficulty with this or any other empirical approach is that while the results may be useful for interpolation@ they will not be useful for extrapolation to conditions other than those of the experiment. Nevertheless@ the empirical treatment of excretion data to estimate body burden is an extremely important-first step toward true exposure integration."