The major issues to be addressed, which are also the most significant in highlighting the differences between chemical and microbial assessments, concern the many scientific uncertainties that arise in the evidence, and in the need to extrapolate from the populations and conditions under which evidence has been collected to those conditions and populations of interest for risk assessment . Included are those that arise because of the need in most cases to rely upon animal studies for hazard and dose- risk information, those related to the need to extrapolate from high dose findings to relatively low dose human exposures, and the uncertainties associated with variabilities in response within and across human populations. These uncertainties require the use of incompletely verified assumptions in virtually all risk assessments. Standardized assumptions are often used, but can be replaced in specific cases in which scientific studies have identified approaches having reduced uncertainty. Key differences between microbial and chemical risk assessments will be summarized.