Metabolism, Storage and Excretion

Deema P, Thompson E, Ware GW. 1966. Metabolism, storage and excretion of C- -endosulfan in the mouse. J Econ Entomol 59 546-550. 

From a toxicological point of view, the critical issue is how much of the toxic form of the chemical reaches the site of action. This will be determined by the interplay of the processes of uptake, distribution, metabolism, storage, and excretion. These processes will now be discussed in a little more detail. 

There are three types of defenses against toxic materials internal, antidotal, and external. Three things can happen once a chemical is taken into the body metabolism, storage, and excretion. Internal defenses are the ability of the body to get rid of a toxic material, sometimes referred to as metabohsm. The body normally excretes waste materials through the feces or urine. Additionally, women can also excrete through the ova and breast mUk. In these instances, the excretions from the mother represent exposure to the offspring. 

The term bioavailability is used to denote the ability of an element to undergo gastrointestinal absorption and then to take part in the normal biochemical processes of transport, metabolism, storage and excretion. 

Kinetic toxicology, also known as metabolic or pharmacologic toxicology, involves toxicants that are transported and metabolized in the body. Such substances are called systemic poisons and they are studied under the discipline of systemic toxicology. Systemic poisons may cross cell membranes (see Chapter 3) and act on receptors such as cell membranes, bodies in the cells, and specific enzyme systems. The effect is dose responsive, and it is terminated by processes that may include metabolic conversion of the toxicant to a metabolic product, chemical binding, storage, and excretion from the organism. 

Having examined the routes by which toxicants enter the body, it is now appropriate to consider what happens to them in the body and what their effects are. The action of a toxic substance can be divided into two major phases, as illustrated in Figure 6.10. The kinetic phase involves absorption, metabolism, temporary storage, distribution, and, to a certain extent, excretion of the toxicant or its precursor compound, called the protoxicant. In the most favorable scenario for an organism, a toxicant is absorbed, detoxified by metabolic processes, and excreted with no harm resulting. In... 

Wilson, K. A., Cook, R.M. (1972) Metabolism of xenobiotics in remnants. IV. Storage and excretion of HEOD in Holstein cows../. Agric. Food Chem. 20, 391-394. 

The new introduced parameter CLir = VA/5 is called clearance, and it has dimensions of flow, volume Xtime-1. The clearance has a bidirectional use and indicates the volume of the solution that is cleared from drug per unit of time because of the drug movement across the plane. For an isotropic membrane, structural and functional characteristics are identical at both sides of the membrane, CLir = CLri. In practice, the term clearance is rarely used except for the irreversible removal of a material from a compartment by unidirectional pathways of metabolism, storage, or excretion. The other new parameter P = T>/8 characterizes the diffusing ability of a given solute for a given membrane, and it is called permeability. Permeability has dimensions of length xtime-1. 

Bioaccumulation can be estimated by a kinetic model. In kinetic models (sometimes called physiological models or physiologically based pharmacokinetic models), consideration is given to the dynamics of ingestion, internal transport, storage, metabolic transformation, and excretion processes that occur in each type of organism for each type of chemical. In kinetic models,... 

Distribution, Storage and Excretion. Hydrocarbons in each of the aliphatic and aromatic fractions are expected to be distributed throughout tissues and organs following absorption. Preferential distribution to fatty tissues occurs especially with aliphatic hydrocarbons. Ingested or inhaled volatile aliphatic and aromatic hydrocarbons in the HC5-EC8 and EC5-EC9 fractions can be eliminated in exhaled breath as unchanged parent compound. Metabolic elimination of aromatic hydrocarbons in each EC fraction predominately occurs via oxidative metabolic pathways involving... 

Although the word "metabolism (Gr. metabole, change) has a rather limited connotation, a "pesticide metabolism study is usually considered in a broad sense to encompass not only the metabolic alterations of the chemical in question but also the absorption, transport, storage, and excretion or elimination of the parent pesticide and its metabolites by the exposed organism. The schematic in Figure 6 shows that pesticide "metabolism" can be considered as more or less synonomous with the toxokinetic phase of a pesticide/organism interaction. Of course, any metabolic transformation that occurs in the gut prior to absorption of the pesticide would be considered, and is in fact, metabolism. 

Metabolism—The absorption, storage, and excretion of the bioflavonoids are very similar to vitamin C. They are readily absorbed into the bloodstream from the upper part of the small intestine. Excessive amounts are excreted primarily in the urine. 

Metabolism—Pertinent facts about the absorption, storage, and excretion of vitamin C follow ... 

Human populations are likely to be exposed to a pollutant through more than one exposure route at a time. Total exposure may combine intake through ingestion of different substances, dermal absorption from surface water and water supply, and inhalation at different locations in the study area (e.g., work, home, recreational areas, commuting routes). Calculation of total exposure requires that the pharmacokinetics (absorption, metabolism, storage, excretion) for different exposure routes are understood for the pollutant of concern. Otherwise, only exposures by route can be combined. 

As the human body is able to store many minerals, deviations from the daily ration are balanced out over a given period of time. Minerals stored in the body include water, which is distributed throughout the whole body calcium, stored in the form of apatite in the bones (see p. 340) iodine, stored as thyroglobulin in the thyroid and iron, stored in the form of ferritin and hemosiderin in the bone marrow, spleen, and liver (see p. 286). The storage site for many trace elements is the liver. In many cases, the metabolism of minerals is regulated by hormones—for example, the uptake and excretion of H2O, Na, ... 

Dehydrogenase Deficiency, Biotinidase Deficiency, and Adrenoleukodystrophy. Catabolism of essential amino acid skeletons is discussed in the chapters Phenylketonuria and HMG-CoA Lyase Deficiency. The chapters Inborn Errors of Urea Synthesis and Neonatal Hyperbilirubinemia discuss the detoxification and excretion of amino acid nitrogen and of heme. The chapter Gaucher Disease provides an illustration of the range of catabolic problems that result in lysosomal storage diseases. Several additional chapters deal with key aspects of intracellular transport of enzymes and metabolic intermediates the targeting of enzymes to lysosomes (I-Cell Disease), receptor-mediated endocytosis (Low-Density Lipoprotein Receptors and Familial Hypercholesterolemia) and the role of ABC transporters in export of cholesterol from the cell (Tangier disease). 

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