ABSTRACT
Pharmacokinetics involves the study of the rate and extent of absorption, distribution, metabolism and excretion of chemicals in biota (Wagner 1975). Inhalation pharmacokinetics relates to the characterization of the time-course of concentration in tissues, blood or excreta of inhaled chemicals and their metabolites. The pharmacokinetics or the processes of pulmonary uptake, tissue distribution, metabolism, urinary and fecal excretion as well as exhalation together determine the amount of inhaled chemicals available for interaction in the tissues. The adverse response in biota is more closely related to internal dose (e.g., concentration of the toxic chemical in the target tissue) rather than inhalation exposure concentration. In fact, dose-response relationships that often appear complex at the exposure dose level become simpler when expressed on the basis of internal dose of the chemical (Gehring et al. 1978, Andersen et al. 1987, Clewell et al. 2002). Figure 19.1 shows an example of refi nement of the dose-response relationship for a volatile organic chemical (VOC) resulting from the use of internal dose. Panel A depicts the relationship between the exposure concentration and the observed cancer response for a VOC, which is neither clearly linear nor nonlinear. However, once the exposure concentration is related to the internal dose (e.g., area under the parent chemical concentration vs time in target tissue), the non-linearity due to pharmacokinetics is clearly evident (Panel B). Consequently, the relationship between the internal dose measures and adverse responses can be established more confi dently (Panel C). One of the major advantages of constructing dose-response relationships on the basis of internal
FIGURE 19.1 Relationship between the exposure concentration and adverse response for a hypothetical volatile organic chemical (Panel A). Panels B and C represent the relationship between exposure concentration and internal dose (area under the parent chemical concentration vs time curve in target tissue) as well as between internal dose and response.
