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 it’s 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 % in relation to liver

1) Liver 100%
2) Adrenal Glands 75%
3) Lungs 30%
4) Kidneys 30%
5) Testes 20%
6) Skin 10%
7) G.I.T. 10%
8) Spleen 5%
9) Throat Muscles 3%
10) Skeletal Muscles 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.