Mixture extrapolation approaches general

For the derivation of the PNEC several approaches have been proposed. Generally these can be categorised into three distinct assessments a conservative, a distributional, and a mixture toxicity approach. In conservative approaches, usually the most (realistic) sensitive endpoint such as LC50 or the known no observed effect concentration (NOEC) is taken and divided by an uncertainty factor (10-100). The selected uncertainty factor value depends on the type of endpoint and the number of available data, and is applied to account for laboratory to field extrapolations, species differences in sensitivities, and similar uncertainties. In distributional approaches, a series of, or all available, literature data are taken and a selected cut-off value is applied to the distribution of these data. The cut-off value may be, e.g., the concentration value that will protect 95% of the species (tested). In general, again an uncertainty factor (usually of 10) is then applied to take into account species differences. In the mixture toxicity approach, a similar mode of action is assumed for the assessment of the combined (additive) effect of the mixture. All relevant mixture components are scaled relative to the most potent one. This results in relative potencies for each component. The total effect of the mixture is then evaluated by... 

Mixture extrapolation can be complex due to the variety of model approaches, the optional tiers, and the different extrapolation targets. Therefore, apart from the technical mixture extrapolation protocols sensu stricto, a general stepwise protocol should be followed. Here, we propose a protocol of 5 steps. 

There are many extrapolation methods, of different complexities, and with different purposes and suitabilities for prospective and retrospective risk assessments. A compilation of the methods is insufficient to guide the choice of procedures to use when assessors need to conduct risk assessments. Therefore, a practical and pragmatic guide to extrapolations and their everyday use is provided in the last chapter. It defines a general stepwise approach to identifying the types of extrapolation (matrix and media, (Q)SARs, mixtures, etc.) that are most relevant for an assessment problem, and it defines an overall approach to the assignment of tiers. 

Another group of theoretical approaches is based on a comparison with the adsorption of gas mixtures. In principle, one may consider adsorption from a binary fluid mixture as an extrapolation of the adsorption from a binary gas mixture to saturation of the two components. This extrapolation covers the least accessible part of the Isotherms, because non-ideality in adsorbate and adsorptive and adsorbate-bulk phase interaction have to be accounted for. General rules are not readily derived, other than those that are so formal as to be of little use in practice. For more simple systems useful limiting laws can be derived. We refer to the literature l. It may be noted that Myers and Sircar developed a consistency test by establishing a relation between surface pressures for the two gases and for the fluid mixture. For some binary mixtures of benzene, cyclohexane, n-heptane and 1,2 dlchloroethane on silica gel they found this relation to apply. 

For processes that involve phase transformation, the general approach is to use the ideal-solution equation for the enthalpy of the liquid and treat the vapor phase as an ideal-gas mixture. This reduces the problem to a calculation of the enthalpies of pure liquid and pure vapor components. If the calculation involves states near the phase boundary, hypothetical states maybe involved, whose properties must be calculated by extrapolation from known real states. As an example, consider the constant-pressure heating of a solution that contains 30% acetonitrile in nitromethane, at 1 bar. This is shown by the line LVon the Txy graph in Figure 11-1. The enthalpy change for this process is... 

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