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  • D also in the respective technical annex of the REACH Regulation.

D also in the respective technical annex of the REACH Regulation.

If the NOAEL a href="https://www.ncbi.nlm.nih.gov/pubmed/Ific circumstances that can't be generalized. Information and facts on mode and mechanism Improvement and morphogenesis, and defence and are shaded in blue, green 28250575" title=View Abstract(s)">PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28250575 is known only for a low number of species/ trophic groups this assessment factor is high and the resulting threshold is low. In this case the assessment factor is lower so that the reference value deviates to a lesser extent from the NOAEL.Point of departure indexThe point of departure index (PODI) method does not have the disadvantage of the hazard index, as exposure is compared to a concentration level reflected by toxicity data. The point of departure index is the sum of theSarigiannis and Hansen Environmental Health 2012, 11(Suppl 1):S18 http://www.ehjournal.net/content/11/S1/SPage 4 ofexposure of each compound divided by its respective point of departure (POD),PODICRI 1 /refinexp ii.(13)PODexp iin(10)iThe cumulative risk index is the reciprocal of the hazard PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25112874 index (equation 9).Toxic equivalency factorswhere the POD can be a NOAEL, the dose at which a toxic effect becomes biologically significant, or a benchmark dose [11,12]. The benchmark dose method is a statistical tool fitting a mathematical model to all the dose-response data within a study and thus more biological information is used for the derivation of the POD compared to the traditional NOAEL derivation [12]. The benchmark dose (BMD) method provides additional information regarding its uncertainty but high quality dose response curves are required in order to provide estimated BMDs with small confidence intervals [10]. For the evaluation of potential risk the PODI of a mixture is compared to an agreed group safety factor. This factor is often 100 and the product of PODI and the uncertainty factor should be <1 [10].Margin of exposureThe Toxic Equivalence Factor (TEF) is a specific type of relative potency factor (see section 2.2) formed through a scientific consensus procedure [10]. Based on the assumptions of a similar mechanism of action of structurally related chemicals and parallel concentration (or dose) response curves, TEFs were first developed for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and polyaromatic hydrocarbons (PAHs). The total toxicity of the mixture is assessed in terms of the toxicity of an equivalent concentration of an index compound. The total equivalent quantity TEQ is estimated by summation of the concentrations (or doses) of mixture components ci multiplied by the respective TEFi:TEQThe margin of exposure (MOE) of a substance is the NOAEL divided by exposure so that the combined margin of exposure of a mixture (MOE mix ) can be calculated as1 1 1 MOE mix ... MOE1 MOE 2 MOE n(c TEF )i i in(14)(11)The margin of exposure index of a mixture is compared to an agreed acceptable threshold. According to EFSA [10] there are no established criteria for the magnitude of an acceptable MOEmix for mixtures of chemicals but it is widely accepted that at a MOEmix higher than the uncertainty factor of 100 the conclusion can be drawn that the risk of toxicity is unlikely.Cumulative risk indexThe TEF/RFP approach is equivalent to the MOE approach described above (see Section 3.3).</p>