Utilizing uncertainty factors in minimal risk levels derivation

The Agency for Toxic Substances and Disease Registry (ATSDR) utilizes chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. During MRL derivation, uncertainty factors (UF) are used. Under current ATSDR methodology, default UFs of 10 are applied to extrapolate from a lowest-observed-adverse-effect level (LOAEL) to a no-observed-adverse-effect level (NOAEL), for interspecies extrapolation and for intraspecies variability. However, chemical-specific toxicity information has sometimes made it necessary and appropriate to deviate from using the standard UF of 10. Since its inception in January 1993 until December 1994, ATSDR's Inter-agency MRL Workgroup has derived 46 inhalation and 67 oral MRLs. When the substance-specific data permitted, the workgroup departed from the default UFs of 10 in 30 specific cases. Specific examples and rationales are presented in this paper.