Quantitative Risk Determination

FIGt 26-58 Nomograph to determine the downwind distance affected hy a release. Adapted from Guidelines for Chemical Process Quantitative Risk Analysis, 1989, p. 90. Used hy permission of the American Institute of Chemical Engineers.)... 

Quantitative risk assessment is now used extensively for determination of chemical and microbial risks in food. This concept helps to systematically and scientifically judge whether certain hazardous compounds may reach unacceptable risk levels when ingested. Quantitative risk assessment can support both quality design and quality assurance but, we discuss it from the assurance perspective. In the past decade, much attention has been paid to assessment of microbial risks due to then-typical differences as compared to chemical risks ... 

The terminology used varies considerably. Hazard identification and risk assessment are sometimes combined into a general category called hazard evaluation. Risk assessment is sometimes called hazard analysis. A risk assessment procedure that determines probabilities is frequently called probabilistic risk assessment (PRA), whereas a procedure that determines probability and consequences is called quantitative risk analysis (QRA). 

Risk is the product of the probability of a release, thepjpbability of exposure, and the consequences of the exposure. Risk is usually described graphically, as shown in Figure 11-15. All companies decide their levels of acceptable risk and unacceptable risk. The actual risk of a process or plant is usually determined using quantitative risk analysis (QRA) or a layer of protection analysis (LOPA). Other methods are sometimes used however, ORA and LOPA are the methods that are most commonly used. In both methods the frequency of the release is determined using a combination of event trees, fault trees, or an appropriate adaptation. 

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. 

The fundamental question of risk assessment for potential human carcinogens requires definition of substances that exceed an evidentiary threshold. Once the scientific evidence establishes a substantial basis for conclusion of known or potential human cancer, it is then in order to determine a procedure for risk quantification. Quantitative risk assessments must always be read with the qualitative evidence of the likelihood of carcinogenicity. 

In order to achieve uniform, transparent, and reliable allergy information on the label, quantitative risk assessment can be applied to set concentration levels for each major allergen and for different product categories that determine whether a product should be labeled precautionary or not. 

This example shows that (1) the mechanistic PK/PD model developed based on literature data of rHu-EPO and predinical information of a new ERA is suitable to provide a better quantification and prediction of the drug disposition and the time course of hemoglobin in adult healthy subjects, and (2) this model can be used to optimize the design of the Phase I studies of new ERAs, with respect to key design features (number of dose levels, selection of dose levels, number of subjects per dose level, PK/PD sampling times). In this way, a quantitative risk-benefit assessment can be obtained by determining the probability of success of a Phase I study with new ERA, conditional on a certain experimental design. 

Because the literature describes several limitations in the use of NOAELs (Gaylor 1983 Crump 1984 Kimmel and Gaylor 1988), the evaluative process considers other methods for expressing quantitative dose-response evaluations. In particular, the BMD approach originally proposed by Crump (1984) is used to model data in the observed range. That approach was recently endorsed for use in quantitative risk assessment for developmental toxicity and other noncancer health effects (Barnes et al. 1995). The BMD can be useful for interpreting dose-response relationships because it accounts for all the data and, unlike the determination of the NOAEL or LOAEL, is not limited to the doses used in the experiment. The BMD approach is especially helpful when a NOAEL is not available because it makes the use of a default uncertainty factor for LOAEL to NOAEL extrapolation unnecessary. 

When an agent is classified as a human or probable human carcinogen, it is then subjected to a quantitative risk assessment. For those designated as possible human carcinogen, the risk assessor can determine on a case-by-case basis whether a quantitative risk assessment is warranted. 

A primary directive of CERCLA is the protection of public health. Because the hazards that exist at Superfund sites tend to be quite variable, it has not been possible to establish specific cleanup criteria for the hazardous substances regulated under CERCLA potential human health effects must be evaluated by quantitative risk assessment on a site-by-site basis. Each Superfund site is assessed individually to determine how clean is clean. The rationale is that the hazard of a contaminant is a function of its potential to reach a receptor (e.g., groundwater, population) and the potential harm to the exposed receptor. The ability of a contaminant to migrate, its potential to degrade, and its distance to a receptor of concern (i.e., the risk), all are site-specific. Only on the basis of such individualized risk assessment is it possible to achieve efficient and cost-effective cleanup of the thousands of hazardous waste sites throughout the US. 

The LLNA also conferred an additional benefit in that the protocol contained an element of dose response and this information could be used to provide an indication of the relative potency of an identified sensitization [27-29], Simply put, the LLNA dose response information is employed to determine the concentration that will generate a threshold positive response and is termed the EC3 value [30], This strength of the LLNA has proven to be of great benefit in terms of improved risk assessment for skin sensitization [31, 32], In particular, it has allowed the establishment of a quantitative risk assessment process (QRA) which establishes safe... 

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