Perspectives and progress on upper levels of intake in the United States.

In the US, recognition of the appropriateness of including an upper level of intake estimate among reference values for nutrient substances was made in 1994 when the Food and Nutrition Board of the Institute of Medicine (IOM) specified the inclusion of an "upper safe" level among its proposed reference points for intake of nutrients and food components. By 1998, a group convened by the IOM had established a risk assessment model for establishing upper intake levels for nutrients, eventually termed the tolerable upper intake levels (UL). A risk assessment framework (i.e., a scientific undertaking intended to characterize the nature and likelihood of harm resulting from human exposure to agents in the environment), as developed in other fields of study, was a logical fit for application to nutrients. But importantly, whereas risk assessment requires that information be organized in specific ways, it does not require specific scientific evaluation methods. Rather, it makes transparent and documents the decision-making that occurs given the available data and the related uncertainties. During the 1990s and beyond, the various IOM committees charged with developing UL for a range of nutrients utilized the risk assessment framework, making modifications and adjustments as dictated by the data. This experience informed the general organizational process for establishing UL but also underscored the dearth of data. For many reasons, undertaking scientific research and obtaining data about the effects of excessive intake have been challenging. It is time to consider creative and focused strategies for modeling, simulating, and otherwise studying the effects of excessive intake of nutrient substances.