Risk assessment endpoints

Ecotoxicological data based on Organization for Economic Cooperation and Development (OECD) guidelines are also required, and the endpoints for aquatic organisms, such as fish, daphnia, algae and aquatic plants, are needed for utilization as part of the risk assessment process. 

The third criterion is that the model should target an endpoint relevant for REACH. Only models that address the endpoints of interest for REACH are appropriate within this purpose. We notice that REACH mentions different purposes for the QSAR models classification and labeling, is one possible target of the model, and risk assessment in another. In the first case models are classifiers in the second case a regression more is more suitable. Indeed, in the first case the... 

For similar reasons, chronic toxicity tests are probably less relevant for use in environmental risk assessment because of the significant discrepancy between the duration of exposure in the laboratory (many days to weeks) and field (usually 1 day or less - see Sect. 5). Sensitivity profiles for chronic toxicity are similar to acute toxicity, although, as would be expected, chronic endpoints are lower than the acute endpoints. Chronic toxicity endpoints for SPs are summarized in Table 3. 

At present, the calculation and mapping of critical loads for heavy metals is only at the beginning and in Europe there are only a few examples of application of methods described in Section 3.2. We will refer to case studies from Germany and Russia as the most characteristic research in this direction. The typical endpoints in these calculations refer to critical concentrations of different heavy metals in the ecosystems. The determination of the given critical concentrations is still uncertain and the relevant risk assessment calculated as an exceedance of critical loads should be based on selecting values of critical concentrations (see 3.2.2). 

Table 4. Percentage of various endpoints contribution to total environmental risk assessment of ecosystem sensitivity to acid deposition in Northern Asia (Bashkin, 1998).

There are no occupational exposure limits for many hazardous substances which may require control of inhalation exposures. The necessary data and other resources required for setting such limits is restricted and unlikely to match the potential demand. A hazard categorisation scheme was, therefore, developed for application within the chemical industry. The scheme used readily-available information on toxicological endpoints to place hazardous substances into a limited range of hazard categories, expressed as Occupational Exposure Bands. These Bands could be used as a basis for risk assessment and the selection of appropriate control regimes. 10 refs. EUROPEAN COMMUNITY EUROPEAN UNION UK WESTERN EUROPE... 

Environmental risk assessment of substances is nowadays based on an evaluation of exposure pathways and concentrations on the one hand and identification and selection of sensitive endpoints on the other. The concept is operationalised by comparing real or estimated (predicted) exposure concentrations (PEC) with calculated no-effect concentrations (NEC or PNEC, predicted NEC). The comparison can be made by calculating the quotient of exposure and no-effect concentration. If the quotient is less than one, then the substance poses no significant risk to the environment. If the quotient is greater than one, the substance may pose a risk, and further action is required, e.g. a more thorough analysis of probability and magnitude of effects will be carried out. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer endpoints (if derived) and the endpoints from which they were derived are indicated and discussed. 

According to USEPA, the key aspect of the ERA is the problem formulation phase. This phase is characterized by USEPA as the identification of ecosystem components at risk and specification of the endpoints used to assess and measure that risk [13]. Assessment endpoints are an expression of the valued resources to be considered in an ERA, whereas measurement endpoints are the actual measures of data used to evaluate the assessment endpoint. 

For every endpoint investigated, the risk assessment for new substances assigns one of four available conclusions (i) the substance is of no immediate concern and need not be considered again until further information is made available in accordance with the requirements of Directive 67/548/EEC, (ii) the substance is of concern and the Competent Authority wiU define information required to refine the assessment and request that it is supplied when the quantity of the substance placed on the market reaches the next supply threshold, (iii) the substance is of concern and the Competent Authority wiU request that defined information is supplied without further delay, and (iv) the substance is of concern and the Competent Authority will immediately make recommendations for risk reduction. 

Gaylor, D.W., R.L. Kodell, J.J. Chen, and D. Krewski. 1999. A unified approach to risk assessment for cancer and noncancer endpoints based on benchmark doses and uncertainty/safety factors. Regul. Toxicol. Pharmacol. 29 151-157. 

US-EPA guidelines for endpoint-specific risk assessments contain guidance on exposure issues of relevance for the particular endpoint. For example, in the US-EPA Guidelines for Reproductive Toxicity Risk Assessment (US-EPA 1996) exposure issues important to reproductive toxicity risk assessment are addressed, and a number of unique considerations regarding the exposure assessment for reproductive toxicity are discussed. 

The first step in risk assessment is to gather health-related information associated with an exposure. Ideally, hazard identification starts before there is significant use of the agent. The structure of the compound is compared with that of compounds with known toxicity profiles. Cell-based studies are often performed to screen for toxicity. Finally, animal bioassays and human studies are performed to characterize and develop a toxicity profile. Multiple health-related endpoints are evaluated to determine if the compound is associated with adverse effects. Advantages of animal studies include experimental control and accurate knowledge of the dose. 

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

Early risk evaluation often just looked at death as the main endpoint, asking if a particular action or exposure led to increases in death or reduced number of working years. Advances in the biological sciences have required that more complex risk analysis be undertaken to evaluate quality of life issues and not just death as an endpoint. The challenge for both risk assessment and risk management will be to take into consideration quality of life and individual values into the decisionmaking process. 

The assessment endpoint should be not only measurable (at least potentially) but also modelable. Defining a modelable endpoint is likely to require close discussion between an assessor (who knows what they can model) and a risk manager (who knows what they want to protect). Sometimes the assessment endpoint is only indirectly related to the management goal, for example, if the assessment endpoint is a risk to individuals, but the aim is to protect population sustainability. In such cases, qualitative inference will be required to interpret the assessment result. This inference will need to be done jointly by the risk assessor and risk manager. It is likely to involve substantial uncertainty, which will have to be taken into account qualitatively when producing a narrative description of the assessment outcome. This step should be identified as part of the conceptual model. 

If the assessment is to be probabilistic, the risk assessor and risk manager should consider together how this influences the definition of the assessment endpoint. Suter (1998) suggests 5 questions for the risk assessor to ask the risk manager to help define the assessment endpoint ... 

Should any assessment endpoints be expressed as probabilities Suter (1998) points out that it can be confusing to use the term probability in defining assessment endpoints because it is unclear whether it relates to variability or uncertainty, so it will be helpful to distinguish these in the discussion with the risk manager. 

Questions 2 and 3 imply a choice between expressing effects in terms of magnitude, frequency, and certainty. In practice, the assessment endpoint may often need to be dehned in terms of 2 or 3 of these dimensions. For example, it may be desirable to estimate the proportion of species (frequency) that will experience different levels of mortality (magnitude), and to provide confidence limits (certainty). Indeed, the risk manager s questions may imply an assessment endpoint with more than 3 dimensions, for example, if it is desired to express frequency in terms of space (e.g., number of hectares) and time (proportion of years). The dimensionality of the assessment endpoint will have major implications for all aspects of the analysis and for communication of results, so it is essential to discuss it carefully with the risk manager at the outset to ensure it meets their needs. 

It is essential to define the assessment scenario within which the assessment endpoint will be assessed. The assessment scenario should specify the spatial, temporal, and ecological boundaries within which the endpoint is assessed, since these have substantial implications for the structure of the assessment model and the scope of the input data. The assessment scenario should also describe those aspects of the ecosystem that are relevant to the assessment, that is, those aspects that have an influence on the mechanisms of exposure and effects that will be assessed. This step is important in all ecological risk assessments it places the assessment activity into the real context of an ecosystem, helps to prevent construction of inappropriate models, and helps with interpretation and communication of results. 

The choice of assessment scenario, like the assessment endpoint, is likely to be implied by the management goal and should be made in close consultation with the risk manager, to ensure it meets their needs. 

For pesticide risk assessments, it may often be necessary to assess impacts of the same pesticide used in different crops, in different seasons, in different geographic regions, and on different species and ecosystems. This will require the use of multiple scenarios and possibly multiple assessment endpoints. 

A set of risk hypotheses that describe predicted relationships among stressor, exposure, and assessment endpoint response, along with the rationale for their selection... 

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