The original tolerable upper intake level (UL) method greatly improved the application of risk assessment to the evaluation of nutrient safety for humans, but a UL is only set where the data establish a hazard resulting from high intakes. Absence of a UL for those nutrients with no established hazard has been misinterpreted by regulators and resulted in overly restrictive policies. To prevent such misinterpretation, the observed safe level (OSL) was developed and defined as "the highest intake with convincing evidence of safety, even if there are no established adverse effects at any level." More recently, a FAO/WHO report gave a similar definition for the highest observed intake (HOI). Another disadvantage of the UL method is the application of arbitrary uncertainty factors (UF). An alternative to the traditional adjustment for uncertainty involves arranging the data in decreasing order of daily intake, followed by evaluation of each trial for quantity and quality of data. Studies are selected downward until no adverse effects are observed in a trial of sufficient quality to justify no further correction for uncertainty (i.e. selection of data that qualify for UF = 1). Thus, the no observed adverse effect level or OSL selected requires no further adjustment for uncertainty. For supplemental intakes of some vitamins, many bioactive substances, and most amino acids, no adverse effects that are clearly related to high intakes have been established, but where the dataset is sufficiently robust, application of the OSL-HOI technique can provide risk assessment values.