Evolution of science‐based uncertainty factors in noncancer risk assessment

Abstract

“Safe”; doses estimated with standard methods by agencies around the world, whether ADIs, ECNCs, MRLs, TDCs, TCs, TIs, RfCs, or RfDs, should be considered as accurate—but imprecise—estimations of doses or concentrations believed to be without risk to populations of humans (including sensitive subgroups). Restated, these “safe”; doses are thought to be below population thresholds for adverse effect, but the degree to which they underestimate the population threshold is generally not known. Part of this imprecision comes from the use of 10‐fold default uncertainty factors. We show research and case studies drawn from a large sample of U.S. EPA and Health Canada risk values where uncertainty factors other than a default value of 10‐fold were used in the estimation of a RfD, RfC, TDI or TC. Percentages for the use of these “data‐derived”; factors vary between 3.6% and 47%. In five case studies, we explicitly review the types of data that have been used to support a change in the default value, why the data support a different UF, and what assumptions have been satisfied, replaced, or how the uncertainty was reduced.

Key words:

• undertainty factors
• risk assessment
• reference dose (RfD)
• non‐cancer
• ADI
• subthreshold dose

Notes

Toxicology Excellence for Risk Assessment (TERA). 4303 Hamilton Ave., Cincinnati, OH 45223; Tel: [phone]; Fax: [phone]; email: [email protected].

International Life Sciences Institute (ILSI), 1126 Sixteenth St., N.W., Washington, DC 200036; Tel: [phone]; Fax: [phone].

This presentation is taken from a text entitled “Evolution of science‐based uncertainty factors in noncancer risk assessment.”; The text was developed by Toxicology Excellence for Risk Assessment (TERA) supported (in part) from the International Life Sciences Institute, Health and Environmental Sciences Institute (HESI). The text has recently been published in Regulatory Toxicology and Pharmacology (Dourson et al., 1996).