title: The Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits.
abstract: The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive occupational exposure limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in exposure from those at the boundary for the onset of adverse effects will yield a safe exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all occupational exposure limit-setting organizations. Five key uncertainties that are often examined include interspecies variability in response when extrapolating from animal studies to humans, response variability in humans, uncertainty in estimating a no-effect level from a dose where effects were observed, extrapolation from shorter duration studies to a full life-time exposure, and other insufficiencies in the overall health effects database indicating that the most sensitive adverse effect may not have been evaluated. In addition, a modifying factor is used by some organizations to account for other remaining uncertainties-typically related to exposure scenarios or accounting for the interplay among the five areas noted above. Consideration of uncertainties in occupational exposure limit derivation is a systematic process whereby the factors applied are not arbitrary, although they are mathematically imprecise. As the scientific basis for uncertainty factor application has improved, default uncertainty factors are now used only in the absence of chemical-specific data, and the trend is to replace them with chemical-specific adjustment factors whenever possible. The increased application of scientific data in the development of uncertainty factors for individual chemicals also has the benefit of increasing the transparency of occupational exposure limit derivation. Improved characterization of the scientific basis for uncertainty factors has led to increasing rigor and transparency in their application as part of the overall occupational exposure limit derivation process.
authors.affiliation: a Education and Information Division, Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health (NIOSH) , Cincinnati , Ohio.
authors.forename: D A
authors.initials: DA
authors.lastname: Dankovic
authors.affiliation: b Global Safety and the Environment, Merck & Co., Inc., Whitehouse Station , New Jersey.
authors.forename: B D
authors.initials: BD
authors.lastname: Naumann
authors.affiliation: c University of Cincinnati , College of Medicine, Department of Environmental Health, Cincinnati , Ohio.
authors.forename: A
authors.initials: A
authors.lastname: Maier
authors.affiliation: d The Toxicology Excellence for Risk Assessment Center of the University of Cincinnati, College of Medicine, Department of Environmental Health, Toxicology Excellence for Risk Assessment , Cincinnati , Ohio.
authors.forename: M L
authors.initials: ML
authors.lastname: Dourson
authors.affiliation: e Institute for Environment, Health, Risks and Futures, Cranfield University, Cranfield, Bedfordshire.
authors.forename: L S
authors.initials: LS
authors.lastname: Levy
mesh_terms: D000818:Animals; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure / Q000592:standards*; D018570:Risk Assessment; D013045:Species Specificity; D014116:Toxicology / Q000379:methods*; D035501:Uncertainty
keywords: adjustment factor; occupational exposure; risk assessment; uncertainty factor