The application of non-default uncertainty factors in the U.S. EPA's Integrated Risk Information System (IRIS). Part I: UF(L), UF(S), and "other uncertainty factors".

The United States Environmental Protection Agency's Integrated Risk Information System (IRIS) includes hazard identification and dose-response assessment values developed by Agency scientists. Uncertainty factors (UFs) are used in the development of IRIS values to address the lack of information in five main areas. The standard UFs account for interspecies uncertainty (UF(A)) and intraspecies variability (UF(H)). The UF(A) addresses uncertainty related to the extrapolation of data from animals to humans, whereas the UF(H) addresses variability amongst individuals (i.e., intrahuman). Additional UFs have been employed to account for database incompleteness, extrapolations from a lowest-observed-adverse-effect level in the absence of a no-observed-adverse-effect level (UF(L)), and subchronic-to-chronic extrapolation (UF(S)). A sixth UF designated as "other uncertainty factors" (UF(O)) has also been applied in place of the UF(L) to account for uncertainty with the adversity of points of departure obtained using benchmark dose modeling. This review will discuss how UF(L), UF(S), and UF(O) have been applied in IRIS assessments, along with the rationale used to describe the choice of UF values that deviate from the standard default of 10.