Urine, toxic materials excreted

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

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. 

Azathioprine is well absorbed from the gastrointestinal tract and is metabolized primarily to mercaptopurine. Xanthine oxidase splits much of the active material to 6-thiouric acid prior to excretion in the urine. After administration of azathioprine, small amounts of unchanged drug and mercaptopurine are also excreted by the kidney, and as much as a twofold increase in toxicity may occur in anephric or anuric patients. Since much of the drug s inactivation depends on xanthine oxidase, patients who are also receiving allopurinol (see Chapters 36 and 54) for control of hyperuricemia should have the dose of azathioprine reduced to one-fourth to one-third the usual amount to prevent excessive toxicity. 

To date, there is limited published material concerning the pharmacokinetics of vanadium compounds in humans. The concentration of vanadium in humans not dosed with the metal is extremely low and at the limits of detection of many of the analytical techniques used. It is not possible to ascertain if the large differences observed in different populations are the result of environmental exposure or experimental variability. Studies using blood have shown vanadium levels of 0.4 to 2.8 pg/L in normal people. The serum contains the largest amount of vanadium with concentration values ranging from 2 to 4 pg/L using atomic absorption spectroscopy [90], The upper limit of vanadium in the urine of normal people was reported to be 22 pg/L, with excretion values averaging below 8 pg/24 h. Vanadium is widely available in nutrition stores for athletes, who believe it to be a nonsteroidal compound that increases muscle mass at a dose of approximately 7 to 10 mg day, without any reports of toxicity [91]. 

As already stated, the source of biological material is also important either due to its accessibility (i.e., noninvasive nature) or due to the fact that the analytes to be measured are restricted to certain locations. Biomarkers can be detected in all biological entities (i.e., fluids, gases, and tissues), and depending on what is to be measured each biological source has a specific niche. For example the fact that alcohol is excreted in the lung, combined with the convenience of using exhaled air, has been exploited for many years in the breathalyzer test as an indirect measurement of blood alcohol levels [5 ]. Stool is commonly used for the detection of parasites and infections. Tears have been proposed to detect and treat ocular toxicity [6], Urine has also been used extensively to measure both renal and non-renal injuries. However, for the most part, blood (serum or plasma) and urine are the most utilized sources. 

Dogs, rats, and rabbits metabolize fluoroacetate compounds to nontoxic metabolites, and excrete fluoroacetate and fluorocitrate compounds peak rate of excretion occurs during the first day after dosing and drops shortly thereafter. Rats dosed with radiolabeled 1080 at 5.0 mg/kg BW had 7 different radioactive compounds in their urine. Monofluoroacetate comprised oifly 13% of the urinary radioactive material, fluorocitrate oifly 11%, and an unidentified toxic metabolite 3% 2 nontoxic metabolites accounted for almost 73% of the urinary radioactivity. Animal muscle usually contained nondetectable residues of any 1080 component within 1-5 days of treatment. Defluorination occurred in the liver by way of an enzymic glutathione-dependent mechanism which in the brush-tailed opossum resulted in the formation of 5 -carboxymethylcysteine and free fluoride ion. A rapid rate of defluorination together with a low reliance on aerobic respiration favored detoxification of fluoroacetate rather than its conversion into fluorocitrate, and may account for the resistance of reptiles to 1080 when compared to mammals. 

Kidney toxicity. The kidneys are the body s principal organ of excretion for water-soluble materials. They are structured in a very complex way to remove larger molecules from the blood by filtration and then to re-absorb most of the water and smaller molecules useful to the body, leaving an aqueous solution of unwanted molecules for excretion as urine. 

There are three major routes for the elimination of foreign compounds the urine, exhaled breath and the faeces. Compounds which enter the body and are then eliminated (in their original form or as their metabolites) are said to be excreted. Elimination also takes account of the voiding of materials which have been swallowed but not absorbed. For example, the faeces contain varying amounts of metals and their compounds which have been ingested but never absorbed—this represents the 90 per cent of the ingested dose which has not been taken up from the gut. The faecal concentration of some potentially toxic metals can therefore be used as an indication of the total amount in the... 

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