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 "dataderived" 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.

Iodine-deficient vegetarians: A hypothetical perchlorate-susceptible population?

“…For example, EPA has made judgments that reduced the default value of 10-fold for intraspecies (i.e., within human) variability for about 3.6% of the RfDs and RfCs listed in the IRIS database (Dourson et al, 1996;US Environmental Protection Agency, 2002) and a similar default reduction has been recommended for perchlorate (Strawson et al, 2004). Examples of RfDs for which uncertainty factor for within human variability was reduced in light of human data on susceptible populations are shown in Table 3.…”

Human pharmaceuticals in US surface waters: A human health risk assessment

“…Uncertainty factors (UFs) are applied, as shown in Eq. 1, to reduce the point of departure dose to a dose where there is reasonable certainty that no eVect will occur (ATSDR, 1996;Dourson et al, 1996;IPCS, 1994) (1)…”

Sicherheitsfaktoren in der Risikobewertung von Chemikalien

“…Die Wahl von arbiträren Faktoren in der Grö-ßenordnung von 100 ist nach Bigwood [3] durch JECFA (Joint Food and Agriculture Organization-World Health Organization Expert Committee on Food Additives) in den 50er-Jahren für den ADI-Wert und durch das WHO Expert Committee for Pesticides Residues durch Lu [4] eingeführt worden. Diese Sicherheitsfaktoren werden verwendet, um in einer quantitativen Risikoabschätzung statistische Unsicherheiten und Modellunsicherheiten zu berücksichtigen.Sie dienen auch dazu, von tierexperimentellen Daten auf die Situation beim Menschen zu extrapolieren sowie die Situation von Mitgliedern besonderer Untergruppen, für die eine besondere Empfindlichkeit angenommen wird, zu berücksichtigen [5,6,7]. Ferner werden von manchen regulatorischen Institutionen weitere "Sicherheitsfaktoren" in die quantitative Risikoabschätzung eingeführt,um Gewichtungen vorzunehmen [8].…”