Absorption of Xenobiotics
Factors influencing absorption of a chemical includes, its physico-chemical properties, its solubility, concentration, circulation, site of absorption, area of absorbing surface and the route of administration. The common routes of absorption for the entrance of xenobiotics into the body are gastrointestinal tract, skin and lungs. Some of the experimental routes for entrance of xenobiotics are intraperitoneal, subcutaneous and intravenous.
1. Gastrointestinal Tract (GIT)
The oral route marks an important route for the entry of xenobiotics in the body system which could be entered either directly or indirectly as environmental contaminants. The chemical properties of any xenobiotic determine whether it will be absorbed in the strongly acid stomach or in the nearly neutral intestine since the absorption takes place along the whole length of the enteric tract. The principles governing the absorption of chemicals from the gastro-intestinal tract are the same as for the passage of chemicals across the biological membranes anywhere else. Drugs, such as nitroglycerine are absorbed better from sublingual route of administration. Most of the chemicals are absorbed through gastro-intestinal tract by non-ionic diffusion across the lipid layer of gastro-intestinal epithelial membrane. Some organic and inorganic ions, sugars, amino-acids are transported by active process. Intestine having pH of about 5.3, absorbs bases more readily and acids are less readily absorbed than stomach. The presence of food can disrupt the absorption of chemicals. Therefore, prolonged fasting may diminish the absorption of various chemicals, that could be due to the deleterious effects upon the epithelium of intestinal wall. Absorption of gastro-intestinal tract may also be retarded if the chemical is unstable in gastro-intestinal fluid or if it becomes bound to food or other gastro-intestinal contents. Biotransformation of gastro-intestinal tract would also affect the absorption of chemicals.
It is the outer most tissue which comes in contact with many chemicals. However, skin retards the diffusion and evaporation of water except at the sweat glands. The epidermis largely limits absorption. The outer layer called as stratum corneum is densely packed with keratin which makes an effective barrier against penetration of water soluble substances. Some xenobiotics like Carbontetrachloride (CCl4) and other organic solvents penetrate the skin readily and causes serious toxic effects. Pesticides like malathion and parathion causes deaths in agricultural workers due to percutaneous absorption. Chloro-vinyl-arsene-dichloride, the mustard gas is readily absorbed through the skin.
Abrasion and removal of stratum corneum which is an effective barrier, causes abrupt increase in the permeability of epidermis for all kinds of molecules. Lipid/Water coefficients of chemicals determine their rate of absorption through the epidermis of skin. The difference in chemical composition of different species also impacts the rate of absorption. DDT is very little toxic to mammals but it is highly toxic to insects whose chitinous exoskeleton is permeable to DDT. Some chemicals are so hazardous that it breaks the barriers of cell and increase their permeability. For example, Dimethylsulfoxide can facilitate the penetration of toxicants through the skin.
Xenobiotics can also enter the body through inhalation of gases or aerosols and enter into the circulation by diffusing across the alveolar membranes. Particle size greatly influence the rate of absorption through the alveolar epithelium. For instance, particle size of uranium dioxide is larger than 3 µm and has no toxic effect when introduced into trachea of rat. Smaller sized particles are more likely to get absorbed in the circulation and damages kidney. Particles larger the 10 µm impact in the pharynx or nasal cavity thus hardly reaches the alveolar region. Particles between 1 and 5 µm often sediment within the bronchiolar region of lung and those which are less than 1 µm can diffuse within the alveoli.
Absorption and excretion of toxic gases and vapours depend primarily on their aqueous solubilities (blood/ partition coefficients). Diffusion of the toxic gas in tissues depends upon the solubility of that gas in the tissue in comparison to that in the blood. The particulates may be removed through the bronchi to GFI. Approximately 80% of the lung contents of a chemical is cleared in this way. Lymphatic route also removes the toxicants from the alveoli.
4. Parental Administration
In experimental studies, the chemicals are injected intravenously or intraperitoneally, subcutaneously or rarely intramuscularly. In intravenous injection, the chemical is put in circulation directly into bloodstream without minimum delay. Intraperitoneal route is also a method which results in the rapid absorption of toxicants due to rich blood supply in the peritoneal cavity due to its large surface area. Chemicals that are administered subcutaneously and intramuscularly have relatively slower rate of absorption.
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