Xenobiotics:Foreign or exogenous chemicals from the surrounding environment which enters in our body & transported to their target

organs is known as Zenobiotics. They are of two types:- 1) Lipophilic & 2) Hydrophilic Liphophilic diffuse more readily than hydrophilic. This transport rate depends upon Partition Coefficient. Partition Coefficient = Solubility in Ocetenol / Solubility in Water Non ionized molecules are more lipophilic while ionized molecules are more hydrophilic. So absorption is more in non ionized particles. Zenobiotics pass from the cell membrane by 4 processes:1) Simple Diffusion by Concentration Gradient. This is most common & simple method & does not require any energy. Lipophilic & non ionized are absorbed by this process. 2) Filtration:- Water, Ionic & Hydrophilic molecules are absorbed through small pores of the cell of Diameter 0.4 nm. 3) Facilitated Diffusion:- This is a Carrier Mediated System & requires energy. 4) Active Transport:- This process allows the absorption of substances against concentration gradient & requires energy. 5) Phagocytosis:- Solids 6) Pinocytosis:- Solution Toxicokinetics:- Study of dynamics (Kinetics), Relationship between the concentration of the chemicals (Toxicons) in the body fluids & tissues and its biological effects. Toxic material is absorbed by 1) Inhalation 2) Ingestion & 3) Skin Absorption----- Goes to Body Fluid Goes to Liver Bio transformation in the liver Goes to target organs OR Lipophilic gets converted into Hydrophilic & eliminated through urine Aims of Toxicokinetics:- Toxicokinetic analysis produces a mathematical description of the dynamics of absorption, distribution & elimination. 1) Inhalation:- 0.5 to 5 micron size is respirable dust. Respiration fraction is 0.5 to 10 micron. Below 0.5 micron cannot settle down due to Downian movement. Absorbed material is phagocytised & through lymph channels goes to lymph nodes, causing lymphadenopathy. 2) Skin Absorption:1) Trans epidermal 2) Appendageal:- Absorption through root of hair follicles & mouth of sebaceous Glands. This is very important route, as most are absorbed by this Route. Biotransformation:- By 2 processes 1) Entoxification & 2) Detoxification Most are detoxified in liver. In few cases the end product of detoxification is toxic. This biotransformation in liver is done by series of enzymes. A group of relatively nonspecific enzymes mainly Cytochrome p45o is plenty in liver, & is a main organ of detoxification. Metabolism ( Biotransformation ) capabilities Organ 1) Liver 2) Adrenal Glands 3) Lungs 4) Kidneys 5) Testes 6) Skin 7) G.I.T. 8) Spleen 9) Throat Muscles 10) Skeletal Muscles % in relation to liver 100% 75% 30% 30% 20% 10% 10% 5% 3% 1%

Our motive is to convert these Lipophilic into Hydrophilic.

There are two Phases of Biotransformation:Phase I :- It involves Oxidation, Reduction or Hydrolysis of the parent compound. In Phase I a polar reactive group introduced into the molecule to increase water solubility, which makes the compound suitable for Phase II. Phase II :- The metabolites of Phase I is conjugated with Glucoronic Acid, Glutathione, Glycene, Sulphates or any other endogenous compound suitable for Phase II. Now they are completely water soluble. Biotransformation:- 1) Detoxification;- The toxicity of the substance is reduced e.g. phenobarbitone is detoxified in liver by hydroxylation to Para Hydroxy Phenobarbitone, which is less toxic. 2) Entoxification:- Here metabolites are Toxic. e.g. Parathions, Organo Phosphorous Compounds. Organo Phosphorous Compounds are relatively non toxic to man & animals. It is rapidly metabolized (activated) by sulphuration to Para Oxon which is very toxic to man & insects. This all is needed for Risk Assessment.