Citation:

Woodall, G., S. Kobylewski-Saucier, R. Shaffer, A. Luke, AND L. Carlson. Comparative Review of Human Health Reference Values of the United States. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 207(1):1-19, (2025). https://doi.org/10.1093/toxsci/kfaf092

Impact/Purpose:

This overview provides a much needed introduction to the full spectrum of reference values available for human health risk assessment. In many situations, especially in the immediate aftermath of a catastrophic release of toxic chemicals, there is a need to be selective in which of the available reference values (health benchmarks, toxicity values, etc.) are to be used to inform the most appropriate action for the evolving needs of an unfolding event; moving from immediate response, thorough remediation, to final return to normalcy. Similarly, this overview supports Program of Regional offices when addressing a risk management (e.g., regulatory) decision by selection of the reference value best suited to inform the decision. The overview breaks out the available values into three major categories: those designed for use with the general public (e.g., noncancer reference dose - RfD and reference concentration - RfC values, and cancer inhalation unit risk - IUR and oral cancer slope factor - CSF values); occupational exposure limits (e.g., OSHA Permissible exposure limits and NIOSH IDLH values); and emergency response values (e.g., acute exposure guideline levels - AEGLs). 

Description:

Human health reference values (HHRVs) developed by US 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 3 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 the selection of an alternate HHRV based on suitability for the assessment scenario from among the available chemical-specific values.

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