Similar mixture approach

The Similar Mixture Approach On a case by case basis a candidate mixture or groups of mixtures could act similarly [1,11], Analogies are used when adequate information is not available for the mixture of concern, and this approach is often applied to complex mixtures that have been extensively investigated, such as coke oven emissions, diesel exhaust, and woodstove emissions. However, information should be available to ascertain that a mixture is sufficiently similar to the mixture of concern. There are no quantitative criteria to decide when a mixture is sufficiently similar, though it is recognized that some key components should be represented in similar proportions [1]. As in the previous approach, the mixture must be treated as an individual chemical because the whole mixture has to be experimentally tested to some extent. 

Identifying the most suitable separation conditions is the main objective of separation scientists. It is easier for skilled chromatographers, but this is a complicated subject for beginners. One approach is to find a chromatogram that exhibits the separation of a similar mixture. However, similar mixtures may have been separated under very different conditions either the separation... 

Nitrene insertion provides a useful approach to fused pyrroles, e.g. Scheme 50 (74JCS(P1)583>. A mixture of a- (11 47%) and y- (158 23%) carbolines results from decomposition of the azide (157 R = N3) in decalin at 170-180 °C. A similar mixture results when (157 R = NQ2) is treated with triethyl phosphite (63JCS42). 4-o-Nitrophenylpyridine... 

Whole mixture approach for common mixtures. This is an option if dealing with a common, and often complex, mixture with more or less constant concentration ratios between the mixture components, for example, coke oven emissions. A reference value (e.g., PNEC) or dose-response relationship can be established for the mixture as if it were 1 (complex) compound, and a safe level can be determined like for single compounds based on toxicity data on the mixture itself or a sufficiently similar mixture. The effect data can subsequently be used in future assessments of mixtures that are identical (e.g., originating from the same source) or sufficiently similar. 

Figure 5.3 Three alternative options to assess the risk of mixtures 1) mixtures can be tested in the field or the laboratory, particularly completely unknown mixtures 2) if toxicity data on (sufficient) similar mixtures are available, the mixture can be evaluated using a reference value, for example, in a PEC/PNEC ratio and 3) mixtures of which the components are known can be evaluated using component-based approaches (mixture algorithms). PEC = Predicted Environmental Concentration, PNEC = Predicted No Effect Concentration.

Sufficiently similar mixtures. Another approach is to use surrogate data on one whole mixture to conduct the risk assessment of another. This applies the concept of sufficient similarity, defined as 2 mixtures close in chemical composition where there are small differences in their components and in the proportions of their components. Key issues for similar mixtures include assessing the similarity of analytical chemistry and toxicological data for mixtures. In this case, an RfD, RfC, or slope factor could be calculated for the mixture of concern using data on a sufficiently similar mixture. This concept is also used in specific applications to groups of similar mixtures that are produced by similar processes, for example, the comparative potency method as applied to diesel exhaust emissions (Lewtas 1985,1988 Nesnow 1990). 

Common Whole Mixtures There are few systematic studies of mixtures that are strictly based on the approach of the mixture of concern or similar mixtures as defined under human risk assessment of mixtures. Most ecological effect studies have more characteristics in common with a component-based or unique whole mixture approach than with the common mixture approach. A rare example of the common whole mixture approach in ecological risk assessment is the hydrocarbon block method. In this case, mixture effects are predicted on the basis of partial characterization of hydrocarbon mixtures. The hydrocarbon block method is used to determine the risks of a total hydrocarbon mixture on the basis of discriminating different chain length fractions of hydrocarbons, for each of which toxicities are known (King et al. 1996). 

Fundamental for both the component-based and whole mixture approaches are 2 concepts of mixture toxicity the concept of CA and the concept of IA or RA. CA assumes similar action of the chemicals in the mixture, while IA takes dissimilar action as the starting point. In practice, this means that CA is used as the reference when testing chemicals with the same or similar modes of action, while IA is the preferred reference in cases of chemicals with different modes of action. 

Background and principles Thin-layer chromatography is the other most commonly used form of planar chromatography and uses a very similar experimental approach to paper chromatography. The principal difference is that this technique relies on the separation of biomolecules from a mixture on the basis of partition and/or adsorption. There is a distinct difference between the process of adsorption and a/isorption, and they are not interchangeable terms Whereas molecules that are a/isorbed are taken up into , those that are adsorbed stick to a surface. So, in thin-layer chromatography, the mobile phase is adsorbed (sticks to) and subsequently moves along the stationary phase. The stationary phase consists of an adsorbent (sticky) layer on a flat plate or sheet. The most commonly encountered adsorbent layers comprise silica gel, alumina (not aluminium) or cellulose, while popular solvents include hexane, acetone and alcohol. 

Early reports of hydroboration reactions often recommended in situ generation of diborane from sodium tetrahydroborate (borohydride) and trifluoroborane etherate or some similar mixture. Indeed, it is still reasonable to use this method for simple hydroborations, provided that nothing more complicated than oxidation of the resultant organoborane is intended. Otherwise, the approach should be avoided, particularly since borane is now commercially available in the form of several Lewis base complexes. 

EPA recommends three approaches (1) if the toxicity data on mixture of concern are available, the quantitative risk assessment is done directly form these preferred data (2) when toxicity data are not available for the mixture of concern, data of a sufficiently similar mixture can be used to derive quantitative risk assessment for mixture of concern and (3) if the data are not available for both mixture of concern and the similar mixture, mixture effects can be evaluated from the toxicity data of components. According to EPA, the dose-additive models reasonably predict the systemic toxicity of mixtures composed of similar (dose addition) and dissimilar (response addition) compounds. Therefore, the potential health risk of a mixture can be estimated using a hazard index (HI) derived by summation of the ratios of the actual human exposure level to estimated maximum acceptable level of each toxicant. A HI near to unity is suggestive of concern for public health. This approach will hold true for the mixtures that do not deviate from additivity and do not consider the mode of action of chemicals. Modifications of the standard HI approach are being developed to take account of the data on interactions. 

With the treatment of gases as individual groups, some binary (or multicomponent) gas-liquid mixtures are reduced to mixtures of only two groups. For example, the carbon dioxide and methanol mixture considered at the conclusion of this section is actually a molecular mixture because both molecules are treated as groups by the UNIFAC approach, Similarly, mixtures of carbon dioxide with benzene or with paraffinic hydrocarbon liquids contain only two groups. The results for such systems are remarkably successful, as will be discussed in this section. The description of mixtures with more than two groups is possible for some of the present models, and the results look promising (Apostolou et al. 1995). 

A solution is ideal if it satisfies the ideal-solution law. No real solution is rigorously ideal, but solutions of similar substances approach ideal-solution behavior as the similarity increases. Solutions of xylene isomers, for example, deviate from ideal-solution law by about 1% at the maximiun. Close members of the same homologous series are often assumed to be ideal. It is not unusual to calculate mixtures of paraffin hydrocarbons with the ideal-solution equation. Ideal-solution law is the basis for ideal K values often used in industry. However, ideal-solution law is of great value in another way, and that is to provide a basis for introducing a correction factor, known as the activity coefficient. 

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