Risk assessment assumptions

Assumptions used in analyzing the output of the method and how final probability v.ilucs tor ose in tlie overall risk assessment were determined, mid... 

Core damage and containment performance was assessed for accident sequences, component failure, human error, and containment failure modes relative to the design and operational characteristics of the various reactor and containment types. The IPEs were compared to standards for quality probabilistic risk assessment. Methods, data, boundary conditions, and assumptions are considered to understand the differences and similarities observed. 

The Pickering A Risk Assessment (PARA) (Ontario Hydro, 1995) is also a level 3 PSA for 1 of the 4 units at Pickering. A difference between PARA and DPSE is that sequences beyond the design basis were modeled using the MAAP-CANDU codes with best estimate assumptions. Other parts of the analysis used licensing-type conservative assumptions. 

Most human or environmental healtli hazards can be evaluated by dissecting tlie analysis into four parts liazard identification, dose-response assessment or hazard assessment, exposure assessment, and risk characterization. For some perceived healtli liazards, tlie risk assessment might stop with tlie first step, liazard identification, if no adverse effect is identified or if an agency elects to take regulatory action witliout furtlier analysis. Regarding liazard identification, a hazard is defined as a toxic agent or a set of conditions that luis the potential to cause adverse effects to hmnan health or tlie environment. Healtli hazard identification involves an evaluation of various forms of information in order to identify the different liaz.ards. Dose-response or toxicity assessment is required in an overall assessment responses/cffects can vary widely since all chemicals and contaminants vary in their capacity to cause adverse effects. This step frequently requires that assumptions be made to relate... 

Much of the attention focused on e.xposure assessment has come recently. This is because many of the risk assessments done in tlie past used too many conseix ative assumptions, wliich caused an ovcrcstimation of the actual exposure. Without exposures there are no risks. To experience adverse effects, one must first come into contact with the toxic agent(s). Exposures to chemicals can be via inlialation of air (brcatliing), ingestion of water and food (eating and drinking), or absorption Uu ough the skin. These arc all pathways to the human body. 

Certain assumptions are usually made about an "average" person s attributes for risk assessments applied to large groups of individuals. List the standard values usually assigned to represent the "average" values for the following. 

More attention lias been recently focused on exposure assessment. Tliis is because many of the risk assessments performed in tlie past used too many and overly conservative assumptions. This in turn, caused an overestimation of the actual exposure. 

If there are specific data germane to the assumption of dose-additivity (e g., if two compounds arc present at the same site and it is known that the combination is five times more toxic than the sum of the toxicitics for the two compounds), then tire development of the hazard index should be modified accordingly. The reader can refer to the EPA (1986b) mi.xiure guidelines for discussion of a hazjird index equation that incorporates quantitative interaction data. If data on chemical interactions are available, but arc not adequate to support a quantitative assessment, note the information in the assumptions being documented for the risk assessment. 

The degree of confidence in the final estimation of risk depends on variability, uncertainty, and assumptions identified in all previous steps. The nature of the information available for risk characterization and the associated uncertainties can vary widely, and no single approach is suitable for all hazard and exposure scenarios. In cases in which risk characterization is concluded before human exposure occurs, for example, with food additives that require prior approval, both hazard identification and hazard characterization are largely dependent on animal experiments. And exposure is a theoretical estimate based on predicted uses or residue levels. In contrast, in cases of prior human exposure, hazard identification and hazard characterization may be based on studies in humans and exposure assessment can be based on real-life, actual intake measurements. The influence of estimates and assumptions can be evaluated by using sensitivity and uncertainty analyses. - Risk assessment procedures differ in a range of possible options from relatively unso-... 

Today, when a pesticide with no detectable residues is registered for use, a Tolerance or maximum residue limit (MRL) is established at the lowest concentration level at which the method was validated. However, for risk assessment purposes it would be wrong to use this number in calculating the risk posed to humans by exposure to the pesticide from the consumption of the food product. This would be assuming that the amount of the pesticide present in all food products treated with the pesticide and for which no detectable residues were found is just less than the lowest level of method validation (LLMV). The assumption is wrong, but there is no better way of performing a risk assessment calculation unless the limit of detection (LOD) and limit of quantification (LOQ) of the method were clearly defined in a uniformly acceptable manner. 

It is advisable, then, in a tiered approach to concentrate first on crops and activities (scenarios) that are considered to be relevant with respect to the expected level of exposure and to exclude those not relevant. Second, whether or not the toxicological properties of the product may lead to general restrictions on re-entry should be investigated. If both the likelihood of reentry and the hazard due to the toxicity of the compound cannot generally be neglected, a risk assessment over several steps should be carried out. The assessment may be based on surrogate data and "worst-case" assumptions at first and then refined, if necessary. One possible approach to a tiered evaluation procedure is presented in Figure 1. 

The Log-Probit Model. The log-probit model has been utilized widely in the risk assessment literature, although it has no physiological justification. It was first proposed by Mantel and Bryan, and has been found to provide a good fit with a considerable amount of empirical data (10). The model rests on the assumption that the susceptibility of a population or organisms to a carcinogen has a lognormal distribution with respect to dose, i.e., the logarithm of the dose will produce a positive response if normally distributed. The functional form of the model is ... 

On the other hand, if the really relevant phenomena are overlooked, then this could lead to incorrect interpretation of the fitted parameters, and, consequently, invalid predictions, e.g. if they form the basis of a risk assessment. As illustrative examples, consider two cases that highlight the range of convenience of a refinement (1) most transient effects cannot be seen for microorganisms with very small radii, but the influence of the transient regime can be relevant in the description of accumulation data and (2) if there is transport limitation (i.e. the FIAM assumption does not hold), the lability of the com-plexation becomes very relevant for both the flux and the depletion of the medium. A decision about which phenomena to keep and which to neglect for the specific biological system under consideration and the specific measured quantity can only be made on the basis of a close interaction between theoretical and experimental studies. 

Mr. Don Clay, Director of the Office of Toxic Substances, discussed the premanufacture review procedures and experience with PMNs to date at a meeting of the Organization for Economic Cooperation on Development (OECD) Chemicals Forum in December, (10). He noted that EPA s chemistry, toxicology, and exposure assessment teams normally complete their preliminary evaluation within a week of receipt of a PMN, and, that preliminary assessment eliminates about 50 percent of the substances as chemicals of low concern. They then proceed to structure activity analysis and reasonable worst case assumptions to assess unreasonable risk or the need for more data. 

In animal experiments exposures can be carefully controlled, and dose-response curves can be formally estimated. Extrapolating such information to the human situation is often done for regulatory purposes. There are several models for estimating a lifetime cancer risk in humans based on extrapolation from animal data. These models, however, are premised on empirically unverified assumptions that limit their usefulness for quantitative purposes. While quantitative cancer risk assessment is widely used, it is by no means universally accepted. Using different models, one can arrive at estimates of potential cancer incidence in humans that vary by several orders of magnitude for a given level of exposure. Such variations make it rather difficult to place confidence intervals around benefits estimations for regulatory purposes. Furthermore, low dose risk estimation methods have not been developed for chronic health effects other than cancer. The... 

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. 

Table III. Summary of CAG Assumptions (Present Exposure) PCE Risk Assessment CAG Assumptions (Full Controls) All Alternative Assumptions (Present Exposure)...

The FDA and EPA believe that the tolerance process is protective of human health because it is based on extensive testing and on a combination of conservative assumptions and risk assessment practices developed using current scientific knowledge. 

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