Multiple pathway modeling

Lee AJ, King JR, Rogers TG (1996) A multiple-pathway model for the diffusion of drugs in skin. IMA J Math Appl Med Biol 13 127-150. 

Single or Multiple Pathways Modeling A single microbial model (one culture) may exhibit the entire complex of divergent routes of mammalian metabolism seen with a particular substrate in numerous mammalian species. For example, Cunninghamella bainieri was shown to produce several known oxidative mammalian metabolites of N-n-propylamphetamine. Alternatively, one culture may exhibit a single route of metabolism in lieu of all others. This is particularly useful if the pathway is minor and/or quantitatively masked by other routes of metabolism in mammals, and thus hard to study. In this case, the ultimate "microbial model" may be a composite of cultures, each exhibiting the individual reactions. 

Its capability to conduct full-chain risk assessment on a common system, which allows for linking the simulation of chemical fate in the environmental media, multiple pathways of exposure and the detailed analysis for multiple effects in different target tissues in human body (by PBPK models). 

Exposure Uptake Biokinetic (IEUBK) model stochastic with probabilistic output sensitivity analysis lead exposure for children (6 months to 7 years old) across multiple pathways, routes, and environmental media, estimates blood lead concentrations (2005e)... 

Exposure assessments generally focus on a single chemical and a single route of exposure. However, there have been recent efforts to examine multiple pathways of exposure. The current approach is to add the single point estimates for each exposure source to arrive at a sum. Research continues on developing new data and exposure models for estimating multiple-pathway exposures. 

Both Models 107 for benzene and 108 for multiple chemicals are based on the Benzene Exposure Assessment Model (BEAM) (Behar et al 1993) to generate benzene or chemical inhalation exposure profiles for different human subgroups. For an estimation of dermal dose, Model 109 is a simple film-thickness -based model like DERMAL (Versar, Inc., 1995). Model 110 estimates multiple pathways exposure (i.e. inhalation and dermal doses) to multiple chemicals from the use of consumer products. 

In particular, this chapter wiU stress the need to look beyond the classic radical chain reaction. Lipid oxidation mechanisms have been proposed based on kinetics, usually of oxygen consumption or appearance of specific products (e.g., LOOK) or carbonyls (e.g., malonaldehyde), assuming standard radical chain reaction sequences. However, when side reactions are ignored or reactions proceed by a pathway different from that being measured, erroneous conclusions can easily be drawn. The same argument holds for catalytic mechanisms, as will be shown in the discussion about metals. In the past, separation and analysis of products was laborious, but contemporary methods allow much more sensitive detection and identification of a broad mix of products. Thus, multiple pathways and reaction tracks need to be evaluated simultaneously to develop an accurate picture of lipid oxidation in model systems, foods, and biological tissues. 

Using this semantic relation, the user may investigate alternative pathways by specifying a different characterization. Consistency is maintained by the multiple-context modeling utility of LCR. 

McKone TE and MacEeod M (2004) Tracking multiple pathways of human exposure to persistent multimedia pollutants Regional, continental, and global scale models. Annual Reviews of Environment and Resources 28 463-492. 

Abkevich, V. I., Gutin, A. M., and Shakhnovich, E. I., Free energy landscape for protein folding kinetics Intermediates, traps, and multiple pathways in theory and lattice model simulations. J. Chem. Phys. 101, 6052 (1994). 

If the field is to move toward more complicated models that include multiple pathways and cell stimuli, a number of hurdles must be overcome. First and... 

Despite detailed and repeated measurements by various techniques, almost no evidence can be found for the formation of (LFe=0) in the cyclidene systems, despite the fact that peroxo complexes form readily and by one route that constitutes the reverse of the reaction of equation 6. The results reported here also stand in contrast to recent studies based on non-heme oxygenase model systems that indicate the possibility of multiple pathways, implying that (hydroperoxo)iron(III) species might have catalytic activity e.g., a) Y.-D. Wu, K. N. Houk, J. S. Valentine, and W. Nam, Inorg, Chem, 31 718 (1992) b) W. Nam, R. Ho, and J. S. Valentine, J, Am,... 

---