Threshold observed effect concentration

TEC, threshold effect concentration, calculated as the geometric mean of the no-observable effect concentration (NOEC) and the lowest-observable effect concentration (LOEC) BA Battery Approach PW porewater WS whole sediments. 

Such threshold values are often estimated using no-observed-effect concentrations or levels (NOECs or NOELs). It might be tempting to substitute the individual ECx values in the CA equation (Equation 4.2) with NOELs in order to calculate a mixture NOEL. But this would imply that all NOELs provoke the same, statistically insignificant effect that is, all of them must have been determined in an identical experimental setup (in terms of number of replicates, spacing of test concentrations, variance structure), which is hardly ever the case. Nevertheless, a range of methods, such as TEFs or TEQs (see Chapters 1 and 5), makes use of a CA-like approach and sums up NOEL-based hazard quotients. This introduces an additional source of uncertainty in the risk assessment, which is fundamentally different from the question of whether CA is an appropriate concept for the mixture of interest. 

The LOEC (lowest observed effect concentration), or threshold level of observed effects, is the lowest test concentration at which a substance is observed to have a statistically significant and unequivocal effect on the test species. The NOEC (no observed effect concentration) is the highest tested concentration below the LOEC where the stated effect was not observed. A chronic toxicity test may include more than one generation of the test organism. 

Acute toxic effects are considered as being threshold effects, i.e., effects for which there are expected to be a threshold of substance concentration below which the effects will not be manifested. For the hazard and risk assessment, it is important to identify those dose levels at which signs of acute toxicity are observed, and the dose level at which acute toxicity is not observed, i.e., to derive a NOAEL for acute toxicity. However, it should be noted that a NOAEL is usually not derived in the classic acute toxicity smdies, partly because of the limitations in smdy design. 

Independent action (IA) assumes that the joint effect of a combination of agents can be calculated from the responses of individual mixture components by adopting the statistical concept of independent events (Bliss 1939). This means that agents present at doses or concentrations below effect thresholds (i.e., 0 effect levels) will not contribute to the joint effect of the mixture, and if this condition is fulfilled for all components, there will be no combination effect. This central tenet of the concept of IA is commonly taken to mean that exposed subjects are protected from mixture effects as long as the doses or concentrations of all agents in the combination do not exceed their no-observed-effect levels (NOELs) (COT 2002). 

Fish Prolonged Toxicity Test - 14 Day Study (OECD 204, 1984) is a variant of the acute fish test used when a longer exposure time is needed, for example when testing highly lipophilic and poorly water soluble substances, and/or when reporting of additional information is considered necessary. The principle of the test is that threshold levels of lethal and other observed effects and NOEC are determined at intervals during the test period. The test requires at least ten fish per concentration plus control(s). 

For ecosystems, the collection of threshold values for NO(A)EL for several species is used to determine a predicted no-effect concentration (PNEC) for each environmental compartment. Environmental monitoring often observes effects that different environmental concentrations have on various ecosystem sub-groups. Laboratory multi-species test systems are available, but are limited in number and rarely appear in EU chemical risk assessments (see [125]). 

Additive effects occur when two or more substances with the same toxicity (i.e., attack the same organ) are present together. The total or additive effect is the sum of the individual effects. Additive effects are observed when mixtures consist of species that are similar, that is, act identically on a target organ. Additive effects may be observed, for example, when a mixture of two compounds, each below the no observed effect level (NOEL) produce a predicted toxic effect when the sum of their concentrations is greater than the threshold level for toxic action. 

If drug effect can be observed direcdy, then the magnitude of effect can be displayed as a function of drug concentration in the form of a dose-response curve. Figure 4.IA shows a typical dose-response curve and some characteristic parameters that describe it. A curve is characterized by a threshold, maximal effect, and slope. The quantifiable parameters of a curve are the... 

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