Exposure, xenobiotics, major

Phenols also constitute a major source of xenobiotic exposure to the body in the form of drugs and environmental pollutants. Oxidative metabolism of these compounds can lead to physiological damage, therefore the metabolism of these compounds is of great interest. LCEC has been a powerful tool for investigating the metabolism of aromatic compounds by the cytochrome P-450 system LCEC... 

The majority of early publications that can be reasonably identified as comprising immunotoxicology reported altered resistance to infection in animals exposed to various environmental or industrial chemicals. Authors logically concluded that xenobiotic exposure suppressed immune function since the immune system is ultimately responsible for this resistance to infection. Subsequent studies demonstrated that suppression of various cellular and functional endpoints accompanied or preceded increased sensitivity to infection, and that administration of known immunosuppressants likewise decreased host resistance. The human health implications of these studies, that chemical exposure reduced resistance to infection, drove the initial focus of many immunotoxicologists on functional suppression, and provided the theoretical and practical underpinnings of immunotoxicity testing. 

Although the emphasis is on drugs, the same principles apply to any xenobiotic agent. The major difference between drugs and other xenobiotics such as environmental toxins is the dose. The dose of common drugs is usually on the order of 100 mg/day and can be more than a gram a day in contrast, exposure to most other xenobiotics is typically much lower. 

Standardized techniques and equipment for such investigations are in widespread use. Unfortunately, the same cannot be said for metabolism investigations in aquatic animals. Most of the world s animals exclusive of the insects —over 200,000 known species -- live at least a part of their lives in water over 100 species have major economic importance and they form the populations most often at risk of exposure to a growing number of chemical pollutants, but science remains largely ignorant of the disposition of xenobiotics by intact, living specimens of even the most common of the aquatic animals. 

The major advantage of an in vitro system is that it represents a simplified system which allows the experimenter to address questions which cannot be tested in vivo. These systems can allow analysis of activation or metabolism at the single enzyme level. They can test proposed pathways of metabolism or activation. Such studies are not practical with in vivo systems. The major disadvantage is that in vitro systems are a simplified system and the results can be easily over-interpreted. In vitro systems cannot model the pharmacokinetics or toxicokinetics of xenobiotic exposure in vivo. In addition, there may be other, unappreciated enzymes or factors which influence metabolism/toxicity in vivo which are not present in the in vitro system. 

The pulmonary system and skin constitute the major routes of entry for xenobiotic materials into the body. The skin has a large surface area of up to two m2 for adults. This large area, along with skin s external exposure, means that it is a common site of contact with toxic substances, especially in the workplace. It has been estimated that about one third of all reported occupational exposures to toxic substances is through skin, and much larger numbers that produce relatively minor symptoms remain unreported.5 Skin maladies constitute a large fraction of occupational and consumer problems with industrial chemicals and consumer products. 

The two major considerations in determining exposure to xenobiotics are the type of sample and the type of analyte. Both of these are influenced by what happens to a xenobiotic material when it gets into the body. For some exposures, the entry site composes the sample. This is the case, for example, in exposure to asbestos fibers in the air, which is manifested by lesions to the lung. More commonly, the analyte may appear at some distance from the site of exposure, such as... 

The two major kinds of samples analyzed for xenobiotics exposure are blood and urine. Both of these sample types are analyzed for systemic xenobiotics, which are those that are transported in the body and metabolized in various tissues. Xenobiotic substances, their metabolites, and then-adducts are absorbed into the body and transported through it in the bloodstream. Therefore, blood is of unique importance as a sample for biological monitoring. Blood is not a simple sample to process, and subjects often object to the process of taking it. Upon collection, blood may be treated with an anticoagulant, usually a salt of ethylenediaminetetraacetic acid (EDTA), and processed for analysis as whole blood. It may also be allowed to clot and be centrifuged to remove solids the liquid remaining is blood serum. 

Smoking, drugs, industrial chemicals and foods, represent the major sources of exposure to xenobiotics for modern man. Because diet furnishes the most variable and continuous array of xenobiotic exposure, the emphasis of this symposium is the... 

The majority of xenobiotics that are absorbed by the body are lipophilic and can permeate through body membranes. The uptake of hydrophilic species by the body, however, be they solvents, pharmaceuticals, or other chemicals are facilitated by the presence of lipophilic species. Kow values predict which chemicals are hydrophiles and which are lipophiles. Exposures to chemical mixtures of lipophiles and hydrophiles will result in the absorption of greater quantities of hydrophiles than would be taken up if these species were present alone. 

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