From the discussion given thus far, it is clear that risk assessment (RA) even as a quantitative process is inadequate without some consideration of how the uncertainty (or safety) factors are determined. Their impact is apparent, in that they were said (in previous slides) to be incorporated into the risk calculation.

It is also intuitive that the uncertainties can be broadly categorized under the two key RA components with which they are actually associated: (1) Toxicity Assessment; and (2) Human Exposure Assessment. Despite such simplicity, a fair account of these uncertainties would require volumes of discussion, for which this series as well as this lecture is certainly not the place.

In the slides that follow, only the uncertainties with some major impact or issues are discussed. It is largey due to the very difficult, lengthy process of resolving many of these uncertainties that a complete risk assessment for any one chemical could take months or years to complete.

Before launching a brief discussion to highlight these major uncertainties, it is important to distinguish here the two confusing terms uncertainty and variability. As pointed out by the National Research Council (1994), "The realms of uncertainty and variability have fundamentally different ramifications for science and judgment: uncertainty forces decision-makers to judge how probable it is that risks will be overestimated or underestimated for every member of the exposed population, whereas variability forces them to cope with the certainty that different individuals will be subjected to risks both above and below any reference point one chooses."