Dose-response relationships characteristics

There are some basic differences between toxic and allergic reactions. The most important differences are (1) an allergic reaction always requires a prior exposure to the compound, and this reaction only occurs in sensitized individuals and (2) a dose-response relationship is characteristic to a toxic reaction, whereas such a relationship is much less clear for an allergic reaction. Even minute doses can elicit an allergic reaction in a sensitized individual (see Fig. 5.42). ... 

Nutrients enter into biological processes that are not characterized by a well-defined dose-response relationship. Therefore, in many cases, the dietary supplement itself is not expected to exhibit a characteristic dose-response curve. 

As has been emphasized so many times in the preceding chapters, these various manifestations of toxicity all display dose-response characteristics, where by response we refer to the incidence or severity of specific adverse health effects. As we demonstrated in earlier chapters, toxic responses increase in incidence, in severity, and sometimes in both, as dose increases. Moreover, just below the range of doses over which adverse effects can be observed, there is usually evidence for a threshold dose, what we have called the no-observed adverse effect level (NOAEL). The threshold dose must be exceeded before adverse effects become observable (Chapter 3). Deriving from the literature on toxic hazards, descriptions of the dose-response relationships for those hazards comprise the dose-response assessment step of the four-step process. 

The accumulation of human data on a wider scale, and in quantitative form, has enabled radiation epidemiology to advance from an essentially descriptive stage to an analytic one in which numerical, dose-spedfic, risk estimates have begun to be treated statistically in order to identify determinants of risk. As presently conceived, these determinants include characteristics of the radiation exposure, underlying dose-response relationships, host factors, other environmental factors, differential tissue sensitivity, time after exposure, and natural levels of incidence. 

Two types of responses from exposure to hazardous substances, called stochastic or deterministic,5 are of concern in risk assessment. The two types of responses are distinguished by the characteristic features of the dose-response relationship, i.e., the relationship between the dose of a hazardous substance and the probability (or frequency) of a response. 

Analysis of Adverse Effect Dose-Response Information. An integrated analysis of all data from animal and human studies that affect the dose-response and blood level-response relationships of adverse events, the method of dose selection, the choice of dose interval, and dosing recommendations in the package insert should be performed. The effect of demographics and other patient characteristics on the dose-response relationships should be explored. 

Physiologically based pharmacokinetic (PBPK) models are a special type of PK model that attempts to provide more definition to the model analysis by incorporating physiological factors into the model design, like tissue volumes, blood flow rates, and species-specific enzyme characteristics that can more accurately differentiate the dose-response relationship for a chemical or drug in one species from that of another species. The power of this approach is to be able to perform laboratory studies, both in vitro and in vivo, in common experimental species... 

Since data on general dose-response relationships are not available in many cases, biological activity is often represented by a single quantitative or even qualitative characteristic. Therefore, many training sets are created with activity... 

Although the targets will be different and the types of effects will vary, the toxic effects of all chemicals are characterized by what the toxicologist calls a dose-response relationship. Increasing dose will increase the severity of the effect targets may also change as dose increases. This phenomenon, which is so important that a whole chapter is devoted to it, is characteristic not only of acute exposures, but of all others as well. 

Pharmacokinetic models involving nonlinear kinetics of the Michaelis-Menten form have the important extrapolation characteristic of being linear at low dose levels. This low dose linearity contrasts with the low dose nonlinearity of the multihit and Weibull models. Each model, pharmacokinetic, multihit, and Ifeibull, has the desirable ability to describe either convex (upward curvature) or concave (downward curvature) dose-response relationships. Other models, stich as the log normal or multistage, are not consistent with concave relationships. However, the pharmacokinetic model differs from the multihit and Heibull in that it does not assume the nonlinear behavior observed at high dose levels will necessarily correspond to the sane nonlinear behavior at low dose levels. 

There are certain characteristics of immune reactions (a) there may be no clear dose-response relationship (b) repeated exposure is normally required (c) the nature of the reaction does not... 

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