Health risk analysis uncertainties

Our assignment for EPA was to apply quantitative risk analysis methods to the determination of risk for a particular chemical. The health risks for perchloroethylene turned out to be highly uncertain, but by using decision analysis concepts we were able to display this uncertainty in terms of alternative assumptions about the dose response relationship. Similar methods might be used to characterize uncertainties about human exposure to a chemical agent or about the costs to producers and consumers of a restriction on chemical use. 

Paustenbach DJ, Meyer DM, Sheehan PJ, et al. 1991. An assessment and quantitative uncertainty analysis of the health risks to workers exposed to chromium contaminated soils. Toxicol Ind Health 7(3) 159-196. 

Johnson BB, Slovic P (1995) Presenting uncertainty in health risk assessment Initial studies of its effects on risk perception and trust. Risk Analysis, 15(4) 485-494. 

Probabilistic analysis Calculations and expression of health risks using multiple-risk descriptors to provide the likelihood of various risk levels. Probabilistic risk results approximate a full range of possible ontcomes and the likelihood of each, which is often presented as a freqnency distribntion graph, thns allowing uncertainty or variability to be expressed quantitatively (USEPA, 1999). 

Interspecies and intraspecies UFs have been used in the development of safe or threshold exposure levels for chronic, noncancer toxicity by health organizations throughout the world. Examples include the acceptable daily intake (ADI) (Lu 1988 Truhaut 1991 Lu and Sielken 1991), the tolerable daily intake (TDI) or tolerable concentration (TC) (Meek et al. 1994 IPCS 1994), the minimal risk level (MRL) (Pohl and Abadin 1995), the reference dose (RfD) (Barnes and Dourson 1988 Dourson 1996), and the reference concentration (RfC) (EPA 1994 Jarabek et al. 1990). The importance of using distribution-based analyses to assess the degree of variability and uncertainty in risk assessments has been emphasized in recent trends in risk analysis. This will enable risk managers to make more informed decisions and... 

See also Delaney Clause Food, Drug, and Cosmetic Act, US Food Quality Protection Act, US Good Laboratory Practices (GLP) Levels of Effect In Toxicological Assessment Pesticides Pharmacokinetics/Toxicokinetics Risk Assessment, Ecological Risk Assessment, Human Health Risk Characterization Toxicity Testing, Alternatives Uncertainty Analysis. 

Thompson KM, Burmaster DE, and Crouch EAC (1992) Monte Carlo techniques for quantitative uncertainty analysis in public health risk assessments. Risk Analysis 12 53-63. 

See also Risk Assessment, Ecological Risk Assessment, Human Health Risk Characterization Risk Communication Sensitivity Analysis Uncertainty Analysis. 

Monte Carlo analysis is a specific probabilistic assessment method that can be used to characterize health risks and their likelihood of occurrence based on a wide range of parameters (Shade and Jayjock 1997). The U.S. EPA s Stochastic Human Exposure and Dose Simulation (SHEDS) model allows for the quantification of exposures based on a probabilistic assessment of multiple exposure pathways and multiple routes of exposure (Mokhtari et al. 2006 US EPA 2003b). Additional applications of probabilistic techniques wiU be discussed in the section below on conducting an uncertainty analysis of reconstructed exposure values. 

Uncertainty assessments in a semi-quantitative risk analysis, with application to health care... 

In this section we present an approach for how to assess the uncertainties related to the assumptions made in the risk analysis. We use an application from health care to hlustrate ideas a model-based risk analysis of a complex operation. 

Kumar A, Xagoraraki I. Human health risk assessment of pharmaceuticals in water an uncertainty analysis for meprobamate, carbamazepine, and phenytoin. Regul Toxicol Pharmacol 2010 57(2-3) 146-56. 

The output of the analysis phase of an ecological risk assessment consists of an exposure profile and a stressor-response profile (Eigure 9.1). The profiles include estimates of uncertainty, which, as in human health risk assessments, are a constant and essential ingredient of ecological risk assessments. The exposure and effect profiles, together with their associated uncertainty estimates, set the stage for the final phase of the risk-assessment process. 

The concept and reality of risk has been around for some time. There are many different types of risk, such as safety risk, hazard risk, mishap risk, schedule risk, cost risk, investment risk, product risk, and sports risk. Risk also involves many contending factors, such as perceived risk, real risk, individual risk, group risk, societal risk, high risk takers, low risk takers, and risk aversion. On the surface, risk appears to be a very simple concept however, risk can easily become very complex due to all the types, factors, possibilities, and considerations involved. Risk and risk management are not just safety concepts. Risk analysis and risk management are used in many different fields, such as finance, project management, and health care, just to name a few. Risk is not about the present, it is about the future. Risk deals with uncertainty and outcomes. 

The uncertainty of risk analysis—the fact that the data do not provide unique answers—allows for a range of perceptions about the nature of chemical hazards and their effects on worker health.. . . Some place concerns about risk within a calculus of economic viednlity others see risk from the point of view of those exposed to hazards. Each view has implications for responsibility and control. ... 

Decision Analysis. An alternative to making assumptions that select single estimates and suppress uncertainties is to use decision analysis methods, which make the uncertainties explicit in risk assessment and risk evaluation. Judgmental probabilities can be used to characterize uncertainties in the dose response relationship, the extent of human exposure, and the economic costs associated with control policies. Decision analysis provides a conceptual framework to separate the questions of information, what will happen as a consequence of control policy choice, from value judgments on how much conservatism is appropriate in decisions involving human health. 

Is the risk of cancer posed by perchloroethylene "unreasonable" under the language of TSCA No clear answer emerges from the illustrative analysis. Whether a risk is unreasonable is not a matter to be determined from scientific evidence on toxicity and exposure, but rather a determination that will hinge on judgment. We concluded from our calculations that the uncertainty in projected annual cancer incidence from PCE was nearly five orders of magnitude, and such large uncertanties in health impacts may be typical for many chemical agents. 

Cox LA Jr. 1996. Reassessing benzene risks using internal doses and Monte-Carlo uncertainty analysis. Environ Health Perspect 104 (Suppl 6) 1413-1429. 

The general equation for risk assessment is the product of exposure and toxic potential. The above discussion, focused on human health exposure assessment, is clearly applicable to the analysis of uncertainty in the determinants and predictions of toxic effect per unit exposure. Indeed the complete assessment of risk and its uncertainty comes from the integrated evaluation of uncertainty associated with both toxicity and exposure. It is simply an extension of the technique demonstrated above with the addition of algorithms for toxic effect yielding a forecasted distribution of predicted risk. 

See also Benchmark Dose Chemical-Specific Adjustment Factor (CSAF) Environmental Protection Agency, US International Programme on Chemical Safety Risk Assessment, Human Health Uncertainty Analysis. 

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