INFLUENCE OF ROUTE OF EXPOSURE
The route of exposure is important parameter that affect the concentration of toxicants at any specific location in the blood or lymph of human body. The time exposure and path of toxicant affects the rate of biotransformation, storage and elimination of chemicals. For Example if a chemical first enters in the liver before moving to the other parts of body than it is biotransformed rapidly and the levels of toxicants downstream are eliminated. This affects the potential toxicity.
The toxicants that enter through Gastrointestinal tract are carried by blood via vascular system to the liver. The rare drugs given by intrapertinocal injection also enters through portal system to the liver. Blood from liver flows to the heart and then goes to lungs before moving to the other organs. The toxicants that enter through GI tract or peritonium are subject to biotransformation or excretion by the liver or elimination by lungs. This is known as first pass effect.
The toxicants enter through lungs or skin enter in blood and go directly to heart and systematic circulation. The toxicant then moves to other organs before going to other liver and it is not first pass effect. A toxicant that enter through the lymph of intestinal tract also don not go in liver first. Instead it is transported in systematic circulation.
The blood level of toxicant depends on site of absorption and rate of biotransformation and excretion.
DISPOSITION MODELS
The integration of all the processes such as distribution, biotransformation and elimination is known as Disposition. Disposition models are used to describe how a toxicant moves in the body with time. These models are also known as Kinetic Models. The types of disposition models are named for the areas of body (compartments) where chemical moves. Examples of compartments are blood, adipose tissue, liver, kidney, bones and brain.
1) ONE COMPARTMENT OPEN MODEL
It describes the disposition of a material rapidly and consistently in the body at a rate and amount that is proportional to the amount that is left in the body. It is known as first order rate and shown as logarithm of concentration of substance in blood as linear function of time.
The half life of the chemical is defined as time required for half of the chemical to be lost in the plasma. Few chemicals follow this one compartment open model.
2) TWO COMPARTMENT OPEN MODEL
In this model the chemical first enters in the first compartment which is blood than it enters into second compartment that is any organ from where it can be eliminated or it returns to the first compartment. As the concentration in first compartment decreases, the concentration in the other compartment increases. The concentration in second compartment decreases when the chemicals is excreted from the body.
The half life of chemical in two compartment open model is known as biological half life. this is the measure for kinetic behavior of a xenobiotic.
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