Risk exposure ratio

Risk exposure ratio (RER) The ratio of the risk exposure to the project cost, the RER is calculated by dividing the TRE by the total project budget or projected cost. Assuming a uniform budget and unit cost based on total cost divided by total number of units, the RER can also be calculated by dividing the ARE by the annual project budget or cost or by dividing the URE by the unit cost. 

The risk characterization procedure will result in a quantitative comparison per substance of the outcome of the exposure assessment and of the effects assessment. This comparison is made through the ratio PEC/PNEC. The generic name for PEC/ PNEC in EUSES is risk characterization ratio (RCR). Other ratios are used in EUSES for the risk characterization such as the margin of safety (MOS) or the ratio of the estimated no-effect or effect level parameter to the estimated exposure level for human subpopulations and the acceptable operator exposure level (AOEL). 

Pharmaceuticals are intended to have human exposure. Furthermore, pharmaceuticals are intended to have biological effects on the people that receive them. Frequently, the interpretation of results and the formulation of decisions about the continued development and eventual use of a drug are based on an understanding of both the potential adverse effects of the agent and its likely benefits, as well as the dose separation between these two. This makes a clear understanding of dose-response relationship critical, so that the actual risk/benefit ratio can be identified. It... 

The toxicity exposure ratio approach, rather than a more rigid standard setting approach (Section 8.2.2), allows greater room for expert judgment because the size of an overall assessment factor is not fixed. Furthermore, this approach can be readily applied to substances for which limited data are available. The risk assessor can decide how wide the MOS should be in the light of the data available. 

Safety or uncertainty factors are often applied at the end of an assessment, for example, as a level of concern to which a risk quotient or toxicity-exposure ratio is compared. 

Guidance to date supports the risk assessment principles for general chemical substances already published by the Commission (1996). Consequently, the risk characterisation simply involves a quantitative comparison of the outcome of the hazard/effects assessment with the exposure assessment. For human risk this involves the calculation of the TER (Toxicity Exposure Ratio) and comparing it with the MOS (Margin Of Safety). For environmental risk the PEC/PNEC ratio (Predicted Environmental Concentration versus the Predicted No-Effect Concentration) for the various environmental compartments. 

Finally, if the registrant can prove that all risks are under control and the substance can be safely manufactured and used, the corresponding initial exposure scenario is defined as the final exposure scenario. In the end, the final exposure scenario is communicated within the framework of extended safety data sheets in order to ensure the safe use of the substance down the supply chain (Caveat The legal text of REACH usually refers to the term exposure scenario while in reality speaking of the final exposure scenario.) By contrast, if the registrant fails to lower the risk characterization ratio below 1, despite the aforementioned refinements and modifications, he must prevent the use of the substance under circumstances where the risks are not controlled. 

The use of chronic inhaled corticosteroid therapy has been of interest for the past decade. Inhaled corticosteroids have an improved risk-benefit ratio compared with systemic corticosteroid therapy. Using the model for asthma, it was hoped that the inhalation of potent corticosteroid would result in high local efficacy and limited systemic exposure and toxicity. 

The outcome of the risk assessment is expressed in real-world effects instead of a toxicity exposure ratio (TER) number, for which it is unclear how protective it is in terms of effects in the field. 

As shown in the risk assessment figure, the decision making takes place at the risk characterisation step, where the results of the environmental distribution, the calculated concentration, and the ecotoxicological data, the effect concentration, come together. The most common way is to divide the predicted environmental concentration by the effect concentration in the acute or chronic situation, called the PEC-PNEC-ratio. In the European Union the toxicological concentration is divided by the predicted environmental concentration revealing the TER the toxicity-exposure-ratio. 

In accordance with the requirements of Annex VI of 91/414/EEC [7], where the basic principles for decision-making are laid down, Toxicity/Exposure Ratios (TER) are to be calculated. Uncertainty factors of 10 (chronic risk) and 100 (acute risk) must be applied for aquatic organisms. For terrestrial organisms, imcertainty factors of 5 and 10 are to be used, respectively. Different approaches exist for the in-crop area and non-target arthropods and bees in general. Uncertainty arises mainly from the fact that only for a few representative species toxicity data are available. If these trigger values are not breached, a listing of an active substance on Annex I or an authorization of a formulated product respectively are possible. 

Birds and mammals may be exposed to toxic effects of active substances following the field use of plant protection products. In current ecotoxicological risk assessments for pesticide registration endpoints, of toxicity tests are compared with estimations of the expected exposure of wildlife species in the field. From the data on toxicity and exposure, a risk quotient (e.g., TER Toxicity Exposure Ratio) is calculated and compared to safety factors (e.g., 10 for acute risk). If the quotient is larger than the safety factor, the risk is considered to be acceptable. On the other hand, if the quotient is below the safety factor, a possible risk is indicated and further refinement of the input parameters is necessary to show that no risk for wildlife species will exist when the substance is applied under practical field conditions. 

A risk characterization comprises a series of evaluations, each pertaining to a specific population, route of exposure, and frequency and duration of exposure. (ECHA refers to this combination of factors as the "exposure pattern") Assessors characterize the risk to human health by comparing the estimated exposure level for a given exposure pattern with the lowest DNEL/DMEL value for that exposure pattern. If the exposure could exceed the DNEL/DMEL, resulting in a risk characterization ratio (RCR) above 1, then the risk could be significant. 

The CSR indicates that the risk characterization ratio is not far below 1 (for human and/or environmental exposure)... 

The exposure assessment (left hand side of Figure 1) and the effects assessment (right hand side of Figure 1) taken together lead to a risk assessment that determines the likelihood and severity of adverse effects in the exposed population (human, animal or the environment). This is conducted by comparing the Risk Characterisation Ratios (RCR) such as Predicted Environmental Concentration (PEC)/Predicted No Effect Concentration (PNEC) - PEC/PNEC for the various ecosystems to be protected or the margin of safety (MOS) for exposed human populations. 

In the case-control design, a group with a disease (cases) is compared with a selected group of nondiscased (control) individuals with respect to exposure. The relative risk in control studies can only be estimated as the incidence rate among exposed individuals and cannot be calculated. The estimator used is the odds ratio, which is the ratio of the odds of exposure among the cases to that among the controls. 

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