Risk assessment variability

Subsequently, the UK Treasury Department (2004) recommended a risk classification that includes hazard characteristics, the traditional risk assessment variables such as probability and extent of harm, indicators on public perception, and the assessment of social concerns. In addition to the aforementioned eight criteria, the Department made an extra effort to define criteria for measuring concern. The list of concerns includes ... 

Hazard analysis and risk assessment systems have been used for many years by certain heavy equipment manufacturers (HEM) in their design processes to achieve inherently safer products. Keep in mind that their principle concern in using the risk assessment method described here is product safety and the avoidance of injury to users of their equipment, or to bystanders. There are variations in the terms used in the several versions of this industry s Hazard Analysis System. In one version, these are the Risk Assessment Variables ... 

An appropriate sampling program is critical in the conduct of a hcaltli risk assessment. This topic could arguably be part of the exposure assessment, but it has been placed within hazard identification because, if the degree of contamination is small, no further work may be necessary. Not only is it important that samples be collected in a random or representative manner, but the number of samples must be sufficient to conduct a statistically valid analysis. The number needed to insure statistical validity will be dictated by the variability between the results. The larger the variance, tlic greater the number of samples needed to define tire problem, ... 

The risk assessment steps and the risk characterization are influenced by uncertainty and variability. Variability arise from heterogeneity such as dose-response differences within a population, or differences in contaminant levels in tlie environment. Uncertainty on tlie other lumd, represents lack of knowledge about factors such as adverse effects or contaminant levels. 

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-... 

From the results of this study, the conclusion can be drawn that the dislodgeable results tend to be variable from site to site and that the mean of the Cenvir term will be dependent on the method of dislodging used on the turf. What is important is the magnitude of the final calculated transfer coefficient, which is also very dependent on the task that was done when generating the Dpot results. The differences produced by the different techniques for collecting the exposure data will affect the risk assessments performed using the data. 

Additionally, the integration of geographic information system (GIS) with analytical data is an effective procedure in addressing the problem of spatial and temporal variability of the different parameters involved in the environmental fate of chemicals. Based on accurate local estimations, GIS-based models would then also allow deriving realistic and representative spatially averaged regional PECs. Table 4 shows some studies that have used GIS-based methodologies to perform a site-specific risk assessment of PECs in different exposed ecosystems. 

Furthermore, knowledge on the variability and uncertainty associated with each component of the model should be addressed, and described. For any risk assessment process, the uncertainty of the component is fundamental. 

While participating in the European Union programme on risk assessment of existing chemicals, Euro Chlor (representing all major European chlorine producers), recognised the need to carry out a detailed risk evaluation on chemicals linked to the production of chlorine. In view of concerns about specific risks of organohalogen compounds to the marine environment as a sink for all watercourses, Euro Chlor focused on this environmental compartment, with emphasis on the North Sea. This sea area has been extensively studied and is controlled by the Oslo and Paris Convention for the Prevention of Marine Pollution (OSPARCOM). For a series of chemicals on lists of concern adopted by the North Sea Conference (1990), risk assessments are being carried out to demonstrate their variable environmental profiles. 

Ecosystem characterization Long-term monitoring should continue in order to enable estimation of natural variability, as well as to establish a baseline against which to evaluate the effects of disturbances. Standard environmental risk assessment approaches may not be useful if the components of the ecosystem in question have not been determined. Further research on... 

The risk assessment comprises an effect assessment (hazard identification and hazard characterization) and an exposure assessment. The principles for the effect assessment of the active substances are in principle similar to those for existing and new chemicals and are addressed in detail in Chapter 4. Based on the outcome of the effect assessment, an Acceptable Daily Intake (ADI) and an Acceptable Operator Exposure Level (AOEL) are derived, usually from the NOAEL by applying an overall assessment factor addressing differences between experimental effect assessment data (usually from animal studies) and the real human exposure situation, taking into account variability and uncertainty for further details the reader is referred to Chapter 5. As a part of the effect assessment, classification and labeling of the active substance according to the criteria laid down in Directive 67/548/EEC (EEC 1967) is also addressed (Section 2.4.1.8). 

As mentioned previously, the assessment of hazard and risk to humans from exposure to chemical substances is generally based on the extrapolation from data obtained in smdies with experimental animals. In the absence of comparative data in humans, a basic assumption for toxicological risk assessment is that effects observed in laboratory animals are relevant for humans, i.e., would also be expressed in humans. In assessing the risk to humans, an assessment factor is applied to take account of uncertainties in the differences in sensitivity to the test substance between the species, i.e., to account for interspecies variability (Section 5.3). If data are available from more than one species or strain, the hazard and risk assessment is generally based on the most susceptible of these except where data strongly indicate that a particular species is more similar to man than the others with respect to toxicokinetics and/or toxicodynamics. Two main aspects of toxicity, toxicokinetics and toxicodynamics, account for the namre and extent of differences between species in their sensitivity to xenobiotics this is addressed in detail in Chapter 5. 

Probabilistic methods can be applied in dose-response assessment when there is an understanding of the important parameters and their relationships, such as identification of the key determinants of human variation (e.g., metabolic polymorphisms, hormone levels, and cell replication rates), observation of the distributions of these variables, and valid models for combining these variables. With appropriate data and expert judgment, formal approaches to probabilistic risk assessment can be applied to provide insight into the overall extent and dominant sources of human variation and uncertainty. 

Chapter 5 of the document reviews the UFs used by UK Government departments, agencies, and their advisory committees in human health risk assessment. Default values for UFs are provided in Table 3 in the UK document with the factors separated into four classes (1) animal-to-human factor, (2) human variability factor, (3) quality or quantity of data factor, and (4) severity of effect factor. The following chemical sectors are addressed food additives and contaminants, pesticides and biocides, air pollutants, drinking water contaminants, soil contaminants, consumer products and cosmetics, veterinary products, human medicines, medical devices, and industrial chemicals. 

A WHO/IPCS (2005) Harmonization Project Document has proposed using chemical-specific toxicological data instead of default assessment factors, when possible. The concept of Chemical-Specific Adjustment Factors (CS AFs) has been introduced to provide a method for the incorporation of quantitative data on interspecies differences or human variability in either toxicokinetics or toxicodynamics into the risk assessment procedure, by modifying the relevant default UF of 10. Incorporation of toxicokinetic or toxicodynamic data becomes possible if each factor of 10 is divided into appropriately weighted sub-factors as suggested by Renwick (1991, 1993) and adopted by WHO/IPCS (1994), see Section 5.2.1.3. 

Gronlund (1992) has investigated methods used for quantitative risk assessment of non-genotoxic substances, with special regard to the selection of assessment factors. Gronlund found that humans, in most cases, seem to be more sensitive to the toxic effects of chemicals than experimental animals, and that the traditional 10-fold factor for interspecies differences apparently is too small in order to cover the real variation. It was also noted that a general interspecies factor to cover all types of chemicals and all types of experimental animals cannot be expected. It was concluded that a 10-fold factor for interspecies variability probably protects a majority, but not all of the population, provided that the dose correction for differences in body size between experimental animals and humans is performed by the body surface area approach (Section 5.3.2.2). If the dose correction is based on the body weight approach (Section 5.3.2.1), the 10-fold factor was considered to be too small in most cases. 

Gronlund (1992) has investigated methods used for quantitative risk assessment of non-genotoxic substances, with special regard to the selection of assessment factors. Gronlund found that the 10-fold factor suggested for interindividual variability probably protects a majority but not all of the population. 

Burin, G.J. and D.R. Saunders. 1999. Addressing human variability in risk assessment - The robustness of the intraspecies uncertainty factor. Regul. Toxicol. Pharmacol. 30 209-216. 

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