Critical pathway analysis

Fig. 3.2. Critical pathway analysis (example) to estimate the impact of arsenic (50 ug/1) and mercury (500 ug/kg ) WHO recommended values...

When the environmentally most critical components within a complete project cycle are identified (e.g. by their property or total amount), the pathway(s) should be analyzed by which these substances may reach critical concentrations in both man and associated foodwebs. This type of risk estimation, known as critical pathway analysis, is primarily based on the evaluation of existing speciation data, as exemplified in Fig. 3.2 for arsenic and mercury (Preston and Portmann 1981). The differentiation of the most toxic forms of both metals unveils rather early the really critical forms and pathways which these metals may take to reach sensitive targets. To focus on total concentrations alone would fail to understand and predict their true nature or to find out the really relevant routes of exposure. 

Teo ED, Brandon NP, Vos E, Kramer GJ (2005) A critical pathway energy efficiency analysis of the thermochemical UT-3 cycle, Int J Hydrogen Energy 30 559-564... 

Gordon et al. (48) recently performed a pathway-based pharmacogenomic study on rectal cancer treated with chemoradiation in which they evaluated 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (drug metabolism, tumor microenvironment, cell cycle control, and DNA repair). They applied the CART analysis and found that a classification tree with four genes (lL-8, lCAM-1, TGF-, and... 

From the somewhat limited discussion presented in this chapter on net energy analysis, the value of conducting NBAs for energy- and synfuel-producing systems is apparent. The effort needed to complete detailed NBAs is a time-consuming task, but can provide the basic information needed to select the critical pathway to higher efficiency systems, and to help determine whether the desired results can be achieved. Without the perspective provided by an NBA, the effort to perfect a biomass energy system can easily be misdirected. 

However, the direct dynamics calculations are computationally expensive, and cannot employ particularly high levels of electron correlation or large basis sets. If certain regions of the potential cannot be treated to within the required accuracy using a computationally affordable level of theory, the results may have unacceptably large errors. Nevertheless, direct dynamics calculations have played and will play a critical role in the discovery and analysis of competing pathways in chemical reactions. 

An informative set of calculations was carried out by Brandt et al, coupled to experimental studies that demonstrated first-order dependence of the turnover rate on both catalyst and H2, and zero-order dependence on alkene (a-methyl-(E)-stilbene) concentration [71]. The incentive for this investigation was the absence of any characterized advanced intermediates on the catalytic pathway. As a result of the computation, a catalytic cycle (for ethene) was proposed in which H2 addition to iridium was followed by alkene coordination and migratory insertion. The critical difference in this study was the proposal that a second molecule of H2 is involved that facilitates formation of the Ir alkylhydride intermediate. In addition, the reductive elimination of R-H and re-addition of H2 are concerted. This postulate was subsequently challenged. For hydrogenation of styrene by the standard Pfaltz catalyst, ES-MS analysis of the intermediates formed at different stages in the catalytic cycle revealed only Ir(I) and Ir(III) species, supporting a cycle (at least under low-pressure conditions in the gas... 

Knowledge of exposure pathways is a critical part of the analysis needed to piece together the human exposure pattern. 

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