Passive diffusion factors affecting

Poorly absorbed compounds have been identified as those with a PSA>140Af Considering more compounds, considerable more scatter was found around the sigmoidal curve observed for a smaller set of compounds [74]. This is partly due to the fact that many compounds do not show simple passive diffusion only, but are affected by active carriers, efflux mechanisms involving P-glycoprotein (P-gp) and other transporter proteins, and gut wall metabohsm. These factors also con-... 

Studies conducted in vivo in humans and in vitro using human skin indicate that benzene can be absorbed dermally. The data show that dermal absorption is not as substantial as absorption following inhalation exposure to benzene vapor or oral exposure. The movement of a substance through the skin to the blood occurs by passive diffusion and has been described mathematically by Fick s law. However, this is an oversimplification of the process of skin absorption various factors (e.g., interaction of benzene with molecules within the skin) affect the transport of the solvent through the skin (Loden 1986). 

The lipid-aqueous partition coefficient of a drug molecule affects its absorption by passive diffusion. In general, octanol/pH 7.4 buffer partition coefficients in the 1-2 pH range are sufficient for absorption across lipoidal membranes. However, the absence of a strict relationship between the partition coefficient of a molecule and its ability to be absorbed is due to the complex nature of the absorption process. Absorption across membranes can be affected by several diverse factors that may include the ionic and/or polar characteristics of the drug and/or membrane as well as the site and capacity of carrier-mediated absorption or efflux systems. 

Thus, the nature of these membranes and the chemical and physical properties of the toxicant in question are important factors affecting uptake. The mechanisms by which chemical agents pass through the membranes include (1) filtration through spaces or pores in membranes (2) passive diffusion through the spaces or pores, or by dissolving in the lipid material of the membrane and (3) facilitated transport, whereby specialized transport systems carry water-soluble substances across the membrane by a lipid soluble "carrier" molecule, which complexes with the chemical. It can be seen then that, as far as the chemical properties are concerned, lipophilicity is the most important factor affecting absorption. 

Another factor which may affect excretion is binding to plasma proteins. This may reduce excretion via passive diffusion, especially if binding is tight and extensive, as only the free portion will be filtered or will passively diffuse into the tubule. Protein binding does not affect active transport however and a compound such as /7-aminohippuric acid (figure 3.18), which is 90% bound to plasma proteins, is cleared in the first pass of blood through the kidney. 

The uptake of lipids across the brush border plasma membrane into the enterocyte is considered to be a transport process that requires no energy [8], The route of transfer of lipids thus has to take place via a process of passive diffusion. A theoretical model for passive lipid solute transfer that takes into account the different factors that affect the rate of transport has been worked out by Dietschy and collaborators [8,68] (cf. Chapter 5). 

Elimination can be accomplished by passive diffusion when external concentrations are lower than internal concentrations favoring outward flux and by enzymatic pathways that convert hydrophobic parent compounds to more polar metabolites that can be more readily excreted by those taxa that possess a kidney or kidney-like organ (vertebrates and invertebrates such as annelids, molluscs, and arthropods). Conversion of the hydrophobic PAH to a more polar metabolite will decrease its ability to diffuse through the gill membrane, thus favoring the excretory route. The rate of elimination may be affected by environmental factors such as temperature and salinity, and by physiological factors, including reproductive state, age, sex, stress, and enzyme induction, in addition to such factors as route of uptake, chemical hydrophobicity, and exposure history. 

There is also the effect of the structure of the porous material. For a nonequilibrium measurement of diffusion, one can consider that there is no straight path for solutes to travel in the direction of the flux. In an equilibrium measurement of intradiffusion, this represents the fact that solutes are not longer subject to a purely random walk. When a solute is near a pore surface, the probabilities for moving in each direction are no longer uniform certain directions are prohibited by the pore wall. For technical precision, then, one should differentiate between a structure factor and a tortuosity. A tortuosity, t, quantitatively describes experimental results in which multiple interactions affect the diffusion. A structure factor, q, quantitatively describes only the effect of pore space geometry and topology on diffusion. Note that for limited conditions—when studying diffusion of small molecules and a passive pore surface—this allows for x cj. 

Atmospheric—Atmospheric corrosion is responsible for a large fraction of the total corrosion in the world. Factors that affect the atmospheric corrosion of materials in a marine environment are the time of wetness, temperature, material, atmospheric contaminants and pollutants, solar radiation, composition of the corrosion products, wind velocity, and biological species [fO]. Atmospheric corrosion of a passive alloy tends to be localized. For electrochemical processes related to corrosion to occur, an electrolyte must be present to allow current to pass via diffusion and electrochemical migration of cations and anions. Seawater is a very conductive electrolyte. The severity of corrosion in an atmospheric environment is related to the time of wetness during which electrochemical processes and corrosion take place. There is also a direct relationship between atmospheric salt content and measured corrosion rates [/O]. 

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