Metabolic transformations rates

Although there is considerable information about metabolic transformation rates of a variety of organic substances in aquatic organisms, it is often difficult to predict metabolic transformation rates in organisms under field conditions. 

Kow, Koc d-1 metabolic transformation rate constant chemical partition coefficient between octanol and water (Kow), and organic carbon and water (K(x )... 

Lm d-1 metabolic transformation rate constant from fish... 

Metabolic transformation rate constant for 2,3,7,8-TCDD in fish (1/day) 0.001... 

Metabolic transformation rate constant for all chemicals in benthic detritovore (1 /day) 0... 

Despite formal differences between various methodologies, any QSAR method is based on a QSAR table, which can be generalized, as shown in Fig. 2.2. To initiate a QSAR study, this table must include some identifiers of chemical structures (e.g., company s ID numbers, first column of the table in Fig. 2.2), reliably measured values of biological activity [or any other target property of interest (e.g., solubility, metabolic transformation rate, etc. ... 

The rate of uptake from blood and by different organs varies widely, and so does the rate of elimination from different organs. Inorganic mercury is characterized by a markedly non-uniform distribution in the body. Compartmentali-zation of mercury within different parts of the organ or in subcellular structures, the binding of mercury to various chemical compounds within the cell, and the metabolic transformation of mercury, complicate the evaluation of distribution. 

As with absorption and distribution, the nature and rate of metabolic transformations vary among individuals and different animal species. Metabolism differences can be extreme, and may be the most important factor accounting for differences in response to chemical toxicity among animal species and individuals within a species. The more understanding toxicologists acquire of metabolism, the more they shall understand the range of responses exhibited by different species and individuals, and the better they shall be able to evaluate toxic risks to humans. 

Comparison of their rate of onset and recovery of a treated mucosa has been made [37]. Fatty acids have strong and fast reactivity and allow for a fast recovery of the barrier function. Bile salts and salicylates are moderate, fast-acting agents with fast barrier-function recovery. Strong surfactants and chelators have strong or moderate reactivity and a slow recovery of barrier function. Solvents like dimethylsulfoxide and ethanol have moderate reactivity and act primarily as agents to improve drug miscibility in an aqueous environment. The enhancers listed above are also effective in the small intestine [22]. Enhancers that are more colon specific include ethylaceto-acetate, which must be first metabolically transformed to enamine [38]. 

Biological. A bacterial culture isolated from the Oconee River in North Georgia degraded 3-nitroaniline to the intermediate 4-nitrocatechol (Paris and Wolfe, 1987). A Pseudomonasstrain P6, isolated from a Matapeake silt loam, did not grow on 3-nitroaniline as the sole source of carbon. However, in the presence of 4-nitroaniline, all of the applied 3-nitroaniline metabolized completely to carbon dioxide (Zeyer and Kearney, 1983). In the presence of suspended natural populations from unpolluted aquatic systems, the second-order microbial transformation rate constant determined in the laboratory was reported to be 4.6 + 0.1 x 10 L/organism-h (Steen, 1991). 

Often decreased first-pass metabolism decreased rate of bio transformation of many, but not aU drugs marked interindividual variation in rate of hepatic metabolism... 

Metabolic transformation to more water-soluble metabolites is necessary for clearance of sedative-hypnotics from the body. The microsomal drug-metabolizing enzyme systems of the liver are most important in this regard, so elimination half-life of these drugs depends mainly on the rate of their metabolic transformation. 

Oxidation. Although most of the common mammals used as experimental animals carry out oxidation reactions, there may be large variations in the extent to which some of these are carried out. The most common species differences are in the rate at which a particular compound is oxidized rather than the particular pathway through which it is metabolized. Most species are able to hydroxylate aromatic compounds, but there is no apparent species pattern in the ability to carry out this metabolic transformation. 

If the rate constant for metabolic transformation (km) in Equation (15) is significant relative to the rate of chemical elimination to water (k2), the steady-state bioconcentration factor will be k, /(k2 + km) and hence lower than k2 /k2, which reflects the situation where the chemical substance is chemically partitioning between the organism and the water. 

Once a chemical enters the body of an animal (based on the route of entry), the chemical is subjected to metabolism by a variety of mechanisms. The toxicity of many chemicals is dependent on the metabolic rate and pattern of the system. Many tissues are capable of metabolizing substances. However, the maximum activities have been found to occur in the liver, followed by the lung, the intestine, the skin, and the kidneys. The nature of the chemical interactions, biochemical interactions, and metabolic transformations help to determine the toxicity of the chemical. A number of authors have written reviews about the biotransformation of many substances.19,25 28... 

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