Dose-response relationship basic concepts

The explanation of the pharmacokinetics or toxicokinetics involved in absorption, distribution, and elimination processes is a highly specialized branch of toxicology, and is beyond the scope of this chapter. However, here we introduce a few basic concepts that are related to the several transport rate processes that we described earlier in this chapter. Toxicokinetics is an extension of pharmacokinetics in that these studies are conducted at higher doses than pharmacokinetic studies and the principles of pharmacokinetics are applied to xenobiotics. In addition these studies are essential to provide information on the fate of the xenobiotic following exposure by a define route. This information is essential if one is to adequately interpret the dose-response relationship in the risk assessment process. In recent years these toxicokinetic data from laboratory animals have started to be utilized in physiologically based pharmacokinetic (PBPK) models to help extrapolations to low-dose exposures in humans. The ultimate aim in all of these analyses is to provide an estimate of tissue concentrations at the target site associated with the toxicity. 

The hormetic dose-response relationship is not only the most fundamental dose-response relationship, but also a basic biological concept with extremely broad evolutionary, biomedical, and toxicological implications. The introduction of this concept into the central core of pharmacology and toxicology educational practices is both long overdue and essential for the development of these respective fields. 

So far, we have discussed the basic concept of a dose-response relationship, how toxic effects are measured, and the types of toxic effects that can occur in a variety of organisms. This chapter introdnces mcmy of the core concepts of toxicology. We have seen that toxicity Ccm differ bcised on differences cunong species. The factors that result in these differences are farther discussed here. The majority of these factors affect toxicity across species in predictable ways. Children cmd the elderly are often considered most susceptible to toxic effects of chemicals the concepts presented here illustrate why this is so. 

This entry presents a discussion of the principles of respiratory toxicology including (1) an historical perspective, (2) approaches used to evaluate respiratory responses to inhaled chemicals, (3) classification of airborne chemicals, (4) concepts of dose-time relationships, (5) factors influencing toxicity of airborne substances, (6) the basic biology of the respiratory system with emphasis on those structures and functions that are involved in toxicological responses, (7) biomarkers of pulmonary effects, (8) toxicological response associated with inhaled chemicals, and (9) assessing the human risk of airborne chemicals. 

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