Fatma Lestari, PhD

OHS Department
Faculty of Public Health
University of Indonesia
 Definition and Concept
 Absorption
 Distribution
 Metabolism /Biotransformation
 Excretion
 Routes of contact/entry of chemicals into the
body
 How chemicals are biotransformed, including
some important biotransformation pathways
 The ways in which chemicals can be excreted
from the body
 The inter-relatedness of disposition and
biotransformation pathways
 What happens after the
chemicals enter the body?
 GASES VAPOURS DUSTS

LUNGS
(INHALATION)
FUMES

RELATIVE
HAZARD
LIQUIDS POTENTIAL
SKIN
(SKIN CONTACT)

GASTRO-
INTESTINAL
TRACT
(INGESTION) SOLIDS
 The rate and mechanism by which a
material is
◦ absorbed
◦ distributed around the body
◦ Biotransformed and
◦ excreted

ADBE / ADME
 BIOTRANSFORMATION
INCREASED
EXPOSURE ABSORPTION OR REDUCED
LIVER TOXIC EFFECT
LUNGS
BONE
BLOOD ACCUMULATION KIDNEY
STOMACH
EXCRETION LUNGS
LYMPH
ACTION
KIDNEYS
SKIN TRANSPORT TARGET
ORGANS
INCREASED
OR REDUCED
TOXIC EFFECT
LOCAL SYSTEMIC
 Entry and exit of chemicals to the body

 Disposition
The processes that determine the ultimate
fate of a chemical once it comes into contact
with the body
Absorption, Distribution, Biotransformation,
Excretion
 Absorption
 Distribution is the process whereby an
absorbed xenobiotic moves from the portal of
entry to other areas of the body.
 Biotransformation
Used to describe the processes by which a
chemical is subjected to chemical change by
living organism
 Excretion
 Disposition is often used in place of
toxicokinetics to describe the time-course of
movement of chemicals through the body
(that is, how does the body dispose of a
xenobiotic?).

 Toxicokinetics is the study of the kinetics of

all toxic substances
 Route of entry
Mucous
Gas, Vapour membranes of the eye
Particulate
Inhalasi

Tertelan
Cairan/
Padatan
Absorpsi kulit
 GASES VAPOURS DUSTS

LUNGS
(INHALATION)
FUMES

RELATIVE
HAZARD
LIQUIDS POTENTIAL
SKIN
(SKIN CONTACT)

GASTRO-
INTESTINAL
TRACT
(INGESTION) SOLIDS
 The rate and mechanism by which a
material is
◦ absorbed
◦ distributed around the body
◦ Biotransformed and
◦ excreted
 BIOTRANSFORMATION
INCREASED
EXPOSURE ABSORPTION OR REDUCED
LIVER TOXIC EFFECT
LUNGS
BONE
BLOOD ACCUMULATION KIDNEY
STOMACH
EXCRETION LUNGS
LYMPH
ACTION
KIDNEYS
SKIN TRANSPORT TARGET
ORGANS
INCREASED
OR REDUCED
TOXIC EFFECT
LOCAL SYSTEMIC
 Distribution is the process whereby an
absorbed xenobiotic moves from the portal
of entry to other areas of the body.
 The substance must again pass through cell
membranes.
 First it passes through the cells lining the
blood capillaries into the circulatory system
 Predominantly via the blood and lymphatic
system
 skin absorption
Skin Contact arteries
Skin veins

absorption by gut
in faeces
Ingestion Faecal Excretion
arteries GI Tract veins

Liver
hepatic artery Biliary Excretion
(Hepatic Metabolism)

absorption by lungs in air

Inhalation Airborne Excretion
pulmonary artery Lung pulmonary vein

aorta Heart vena cava

hair, sweat
arteries
Other Tissues veins Other Excretion saliva, milk

In urine

renal artery Kidney renal vein Renal Excretion

 Routes of absorption, distribution, and excretion of
toxicants in the body

Adopted from Rozman and Klaasen, Ch. 5. Disposition. In “The Basic Science of Poison
 Biotransformation
The body changes (transform) the substance
into a new chemicals (metabolites)
 Biotransformasi adalah proses dimana suatu bahan
kimia mengalami transformasi (perubahan) dari dari
suatu bahan menjadi bahan lainnya (metabolit)
melalui reaksi biokimia.

 Proses ini melibatkan detoksifikasi/bioaktivasi

sehingga bahan tersebut menjadi lebih mudah larut
dalam air untuk mempermudah eliminasi. Proses ini
sebagian besar terjadi pada hati.

 Detoksifikasi  menjadi kurang berbahaya

 Bioaktivasi  menjadi lebih berbahaya
 General Scheme of Xenobiotic
Biotransformation

Lipophilic Hydrophilic
(parent compound) (metabolite)
1) Decrease biological activity
Biotransformation 2) Increase excretability

Metabolites Metabolites
Phase I Phase II
size
Bioactivation polarity ionization
Detoxification
Detoxification functionality water solubility
Increase excretability
 It increases the potential of the foreign
compound to being more water
soluble;

 It adds or exposes functional groups

which
 Assist in more Phase I biotransformation
reactions, or
 Permits Phase II biotransformation
reactions.
Conjugation reaction include:
 Glucuronidation (Glucuronyltransferases);
 Sulphation (Sulphotransferases);

 Amino acid (mainly glycine, glutamine,

taurine) conjugation;
 Glutathione reactions (Glutathione S-
transferases);
 N-Acetylation (N-Acetyltransferases);

 O-Methylation (O-Methyltransferases).
Reaction Localization
 Excretion
The substance or its metabolites
leave the body
 Compounds (metabolised or not) ultimately are
eliminated. There are several routes
◦ Renal (via the kidneys).
◦ Biliary (via the liver, GIT & faeces).
◦ Pulmonary (exhaled).
◦ Secretory (in body fluids)
Lipophilic toxicants
cannot partition into
 Major routes: aquoes media
◦ kidney (urine) (PCB,
Aquoes media
◦ Digestive tract (feces) Organochlorine pesticide,
solvents)
 Minor routes: Bioaccumulation
◦ Respiratory tract
◦ sweat
1.Urin
2.Udara pernafasan yang dikeluarkan
kembali (Expired air)