Dose-response assessment, description

Hazard characterization (or dose-response assessment) is the qualitative and, as far as possible, quantitative description of the inherent properties of an agent or situation having the potential to cause adverse effects. This step should include a dose-response assessment that describes the severity of adverse effects (the responses) related to the amount and condition of exposure to an agent (the dose). 

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. 

Risk characterization provides for both qualitative and quantitative descriptions of risk. The step involves integrating the results of the hazard identification, dose-response assessment, and exposure assessment to characterize risk. Often, a direct comparison between exposure criteria developed in the first two steps and the results of the exposure assessment (concentration in the environmental media or the estimated dose, as appropriate) provide a basis for determining whether risks are acceptable. Typically, if criteria are exceeded, the risk is not acceptable. What is defined as acceptable, as well as the way risk is expressed, is often a... 

The NRC document calls for hazard identification, dose-response assessment, exposure assessment, and risk characterization. In an effort to place descriptive experimental toxicity results in a clearer perspective and place more emphasis on evaluation, this outline deviates slightly from the NRC document and calls for hazard evaluation, hazard extrapolation, exposure assessment and risk characterization. In addition, a few comments on risk acceptability are given. Exposure assessments have been adequately discussed elsewhere in this symposium and will be discussed here only as they relate to hazard identification, evaluation, extrapolation and risk characterization. 

Although testing of the whole mixture as such seems to be the proper way to approach the risk assessment of exposure to that mixture, it will not provide data on combined actions and/or interactions between the individual components of the mixture. Even if the effect of the mixture is compared with the effects of each individual component at comparable concentrations, this will not allow a description of potential synergism, potentiation, or antagonism, and it is even doubtful that deviations from additivity can be concluded. This can only be achieved if dose-response curves are obtained for each of the single compounds. 

Biomarkers are used at several stages in the risk assessment process. Biomarkers of exposure are important in risk assessment, as an indication of the internal dose is necessary for the proper description of the dose-response relationship. Similarly, biomarkers of response are necessary for determination of the no observed adverse effect level (NOAEL) and the dose-response relationship (see below). Biomarkers of susceptibility may be important for identifying especially sensitive groups to estimate an uncertainty factor. 

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