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4 Uncertainty and Variability: The Recurring and Recalcitrant Elements of Risk Assessment
Pages 93-126

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From page 93...
... . Other topics identified in the committee's charge whose improvement requires new consideration of the best approaches for addressing uncertainty and variability include the cumulative exposures to contaminant mixtures involving multiple sources, exposure pathways, and routes; biologically relevant modes of action for estimating dose-response relationships; models of environmental transport and fate, exposure, physiologically based pharmacokinetics, and dose-response relationships; and linking of ecologic risk-analysis methods to human health risk analysis.
From page 94...
... , it is evident that risk assessors must establish procedures that build confidence in the risk assessment and its results. EPA builds confidence in its risk assessments by ensuring that the assessment process handles uncertainty and variability in ways that are predictable, scientifically defensible, consistent with the agency's statutory mission, and responsive to the needs of decision-makers (NRC 1994)
From page 95...
... The committee notes that elements of exposure assessment are not addressed extensively
From page 96...
... . in further chapters, as compared with other steps in the risk-assessment process, given our judgment that previous reports had sufficiently addressed many key elements of exposure assessment and that the exposure-assessment methods that EPA has developed and used in recent risk assessments generally reflect good technical practice, other than the overarching issues related to uncertainty and variability analysis and decisions about the appropriate analytic scope for the decision context.
From page 97...
... Uncertainty: Lack or incompleteness of information. Quantitative uncertainty analysis attempts to analyze and describe the degree to which a calculated value may differ from the true value; it some times uses probability distributions.
From page 98...
... It is the risk assessor's job to communicate not only the nature and likelihood of possible harm but the uncertainty in the assessment. One of the more significant types of uncertainties in EPA risk assessments can be characterized as "unknown unknowns" -- factors that the assessor is not aware of.
From page 99...
... The Environmental Protection Agency's Use of Available Methods for Addressing Uncertainty EPA's treatment of uncertainty is evident both in its guidance documents and from a review of important risk assessments that it has conducted (EPA 1986, 1989a,b, 1997a,b,c, 2001, 2004a, 2005b)
From page 100...
... , both uncertainty and variability in different components of the assessment (emissions, transport, exposure, pharmacokinetics, and dose-response relationship) are combined by using an uncertainty-propagation method, such as Monte Carlo simulation, with two-stage Monte Carlo analysis utilized to separate uncertainty and variability to the extent possible.
From page 101...
... However, it is important to recognize that there are some uncertainties in environmental and health risk assessments that defy quantification (even by expert elicitation)
From page 102...
... For example, in its regulatory impact analysis of the National Ambient Air Quality Standard for PM2.5 (particulate matter no larger than 2.5 μm in aerodynamic diameter) , EPA did not use the outputs of the expert elicitation to determine the confidence interval for the concentration-response function for uncertainty propagation but instead calculated alternative risk estimates corresponding to each individual expert's judgment with no weighting or combining of judgments (EPA 2006b)
From page 103...
... has proposed four tiers for addressing uncertainty and variability in exposure assessment, from the use of default assumptions to sophisticated QUA. The IPCS tiers are shown in Box 4-4.
From page 104...
... Lower-tier uncertainty analysis methods can be used in a screening step to determine whether the information is adequate to make decisions and to identify situations in which more intensive quantitative methods would be necessary. Special Concerns about Uncertainty Analysis for Risk or Cost-Benefit Tradeoffs In making risk comparisons or cost-benefit determinations, consistency in addressing uncertainty in the risks, costs, and benefits being compared is particularly important, and fuller descriptions of uncertainty than provided by an upper confidence limit are also important.
From page 105...
... A third option is to address uncertainty with default parameters and a "default model such that there is no explicit quantification of model uncertainty." The first option has the problem of demanding detailed probabilistic analyses among one or more models that include potentially large numbers of parameters whose uncertainties must be estimated, often with little information. Such problems are compounded when models are linked into a highly complex system.
From page 106...
... 106 SCIENCE AND DECISIONS: ADVANCING RISK ASSESSMENT BOX 4-5 Examples of Uncertainties for Comparisons of Discrete and Continuous Possibilities Example 1: Discrete Consider two quantities, A and B -- they could be two disparate risks being compared, a "target" risk and an "offsetting" risk, or a benefit estimate (A) and the corresponding cost estimate (B)
From page 107...
... When done in a manner that makes effective use of existing science and that is understandable to stakeholders and the public, models can be very effective for assessing and choosing amongst environmental regulatory activities and communicating with decision-makers and the public." The present committee agrees. Committee Observations Regarding the Treatment of Uncertainty Although EPA has developed methods for addressing parameter uncertainty, particularly for exposure assessment, the remaining challenge is to address uncertainties that are difficult to capture with probability distributions and to provide guidance for the level of detail needed to capture and communicate key uncertainties.
From page 108...
... For example, probabilistic approaches, such as Monte Carlo methods, can be used to propagate variability throughout all components of a risk assessment, expert elicitation can be used to characterize various percentiles in a distribution, and the level of analytic sophistication should be matched to the problem at hand. But the key difference between uncertainty analysis and variability analysis is that variability can only be better characterized, not reduced, so it often must be addressed with strategies different from those used to address uncertainty.
From page 109...
... Stochastic 100:1 Estimated with two-stage clonal model. Increased Heidenreich 2005 liver-cancer risk due to stochastic effects (in 0.1% of population compared with median)
From page 110...
... 110 SCIENCE AND DECISIONS: ADVANCING RISK ASSESSMENT sensitivity that have been reported in the literature. The factors are similar to effect modifiers in epidemiology, in that they modify the effect of another factor on a disease.
From page 111...
... . Guidance in addressing the generalizability of risk estimates derived from occupational studies to the general population is not provided.
From page 112...
... The committee encourages EPA to quantify more explicitly variations in exposure and in dose-response relationships. The tiered approach to variability assessment discussed in the 2005 guidelines, with multiple risk descriptions for different susceptible subgroups, is a step in the right direction but falls short of what is needed.
From page 113...
... Because hazard assessment typically involves a statement or classification regarding the potential for harm, the uncertainty in hazard is not captured well by probability distributions. A formal analysis of hazard uncertainty often requires expert elicitation and discrete probability to communicate uncertainty.
From page 114...
... Many risk assessments in EPA use emission models other than those found in AP-42, but most emission estimates suffer from similar issues related to limitations of validation and unacknowledged uncertainty and variability. For example, traffic emissions are characterized with models, such as MOBILE6, in which the estimates are derived from traffic-flow data and calibrated with dynamometer studies on specific vehicles.
From page 115...
... . For risk assessments, exposure assessment should characterize the sources, routes, pathways, and the attendant uncertainties linking source to dose.
From page 116...
... Through the 1990s, there was increasing emphasis on an explicit and quantitative characterization of the distinction between interindividual variability and uncertainty in exposure assessments. There was also growing interest in and use of probabilistic simulation methods, such as those based on Monte Carlo or closely related methods, as the basis of estimation of differences in exposure among individuals or, in some cases, of the uncertainty associated with any particular exposure estimate.
From page 117...
... Many of the above conclusions for exposure assessment are applicable to dose assessment, but with the recognition that there will be greater variability in doses than exposures across the population as well as greater uncertainty in characterizing those doses. For monitoring, there have been limited but important efforts in recent years to develop comprehensive databases of tissue burdens of chemicals in representative samples of the human population (for example, the National Health and Nutrition Examination Survey [NHANES]
From page 118...
... For carcinogens, it has generally been assumed that there is no threshold of effect, and risk assessments have focused on quantifying their potency, which is the low-dose slope of the dose-response relationship. For noncancer risk assessment, the prevailing assumption has been that homeostatic and other repair mechanisms in the body result in a population threshold or low-dose nonlinearity that leads to inconsequential risk at low doses, and risk assessments have focused on defining the reference dose or concentration that is sufficiently below the threshold or threshold-like dose to be deemed safe ("likely to be without an appreciable risk of deleterious effects")
From page 119...
... To confront the issue, EPA should develop guidance for conducting and establishing the level of detail in uncertainty and variability analyses that is required for various risk assessments. To foster optimal treatment of variability in its assessments, the agency could develop general guidelines or further supplemental guidance to its health-effects
From page 120...
... . In developing guidance for uncertainty analysis, EPA first should develop guidelines that "screen out" risk assessments that focus on risks that do not warrant the use of substantial analytic resources.
From page 121...
... In particular, this process should encourage risk assessments to characterize and communicate uncertainty and variability in all key
From page 122...
... 1999. The Use of Probabilistic Techniques in Exposure Assessment: A Handbook for Dealing with Variability and Uncertainty in Models and Inputs.
From page 123...
... 1992. Guidelines for Exposure Assessment.
From page 124...
... 2005c. Regulatory Impact Analysis for the Final Clean Air Interstate Rule.
From page 125...
... 2004. IPCS Risk Assessment Terminology Part 1: IPCS/OECD Key Generic Terms used in Chemical Hazard/Risk Assessment and Part 2: IPCS Glossary of Key Exposure Assessment Terminology.
From page 126...
... 2006b. Health Risks from Exposures to Low Levels of Ionizing Radiation BEIR VII.


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