Comparative Review of Human Health Reference Values of the United States

Human health-based reference values (HHRVs) developed by United States (U.S.) governmental agencies and professional organizations are derived for specific purposes related to their organizational or statutory mandates, and for individual chemicals or substance groups (e.g., manganese compounds). Choosing an appropriate chemical-specific value should be based on the risk assessment need and the specific exposure context, along with a basic understanding of the various types and the intended purposes of each available HHRV. In this overview, HHRVs have been broadly organized into three main categories: Values for the general public; occupational exposure limits; and emergency response values. The goal of this overview is to equip the reader with a greater understanding of HHRVs, how they are meant to be applied, and key aspects to consider in selecting the most appropriate value. These key aspects include target population (e.g., general public of all ages vs. working-age adults), duration and frequency of exposure, health effect severity, confidence in the data set, use of well-documented and contemporary derivation methods, transparency and documentation of the value derivation, and the thoroughness of the review process. Chemical- and exposure scenario-specific needs should determine which HHRV is most appropriate; however, a most appropriate HHRV may not be available for every chemical and situation. Therefore, we present both considerations and limitations to guide selection of an alternate HHRV based on suitability for the assessment scenario from among the available chemical-specific values.