BASE OF TOXICOLOGY

1. Preface :
Toxicology is study about the characteristic of
chemical toxin toward human being
and environment.
Xenobiotic (xeno = strange)
Chemical : - Drug
Directorate of drug and
food
- food
supervision
(POM) Health Dept.
Another chemicals :
Arranged by Foundation of Environmental
Protection Agency in AS.

Xenobiotic research animal experiment

data

Extrapolation
animal human

Paracetamol liver failure fatal

chemical therapy effect doses

adequate farmakoterapeutik

Benefit of antidotum consist of:

-Norit
-Tanat acid
-Mg Oksida

Uncertain, beside that combination sometime

mutual antagonisme.
A part of norit activities disappeared by Mg
oksida.

Congenital defect def. Enzim G6PD INH,

primakuin, suksinilkolin Hemolysis

2. Toxicology Experimental
R/ hypertensi and contraception effect
Carsinogenik and teratogenic
2.1 Pharmacokinetic Test
Metakolin and karbakol need long capacity
was effective, also toxic
- Excretion : origin and metabolite
- Plasma capacity
- Half period
- Characteristic distribution
- Biotransformation and excretion product

2. 2 Pharmacodynamic test
2. 3 Evaluate the chemical safety
There are no effect Level (NEL)
NEL : Total concentration in chemical found or
observation, there are no defect, no change of
organ function, no change of growth.
Safety : 10 x 10 different with human

different with animal and man

10 x 10

ADI (Acceptable Daily Intake)

100

ADI = NEL
100

mg/kg BB/hr

If chemical material was accumulated in organ

Not used as additional food.
MPC (Maximal Permission Concentration)
MPC =

ADI x BW (kg)
Food factor (kg)

2. 4 Toxicities Test :
Experiment animal : mouse, dog, pig, monkey
guinea pig, 2 3 month, BW 180 200 gr,
acclimatises in lab, healthy.
Toxicities acute : Single dose Experiments
evaluated after 3-14 days,
1. 10 mg/kgBB
3. 22,5 mg/kgBB

2. 15 mg/kgBB
4. 33,75 mg/kgBB

- BW
- Age of mouse
- Dissolved substance
- Male
- Female
- Environment
- Evaluation : - LD50
- Behavior
- Stimulation/depression CNS
- Activist motoric from respiration
Liver failure, kidney and system homoeopathic
3 days

 Toxisitas long period :

Frequently experiment during 1 3 months
(subakut)
3 - 6 months
(chronic )
Lifelong studies :
6 months
Toxicities long period Research carcinogenic
Experiment toxicities acute toxic effect
Experiment toxicities chronic tested drug
safety

Estimated drug safety/ chemical

substance

Evaluate drug safety/chemical substance can

do by :
1. Determine LD50
2. Experiment of toxicities subacute and
chronic for determining NEL
3. Experiment of carcinogenic, teratogenic and
mutagenesis
(Part of routine filtering for safety)
Change :

- Accumulation
- Tolerance
- Metabolism
- Physical defect must be detected

Excretion : blood chemical, urine, defecate

 Mekanism of drug toxicities :

Pharmakodynamic toxic reaction
Heart medicine block conduction AV

block AV (toxin)
Hypnotic coma
AgAb reaction allergy reaction
Not pure of hormone toxic reaction
Brown Tetracycline epi anhidrotetrasiklin
(damage of kidney).
Damage of kidney and liver disturb
indirectly easy to be toxicities.

2. 5 Relation with animal and human

experiment.
Experiment to man : doses
- Toxic effect
- Network trouble
Value of prediction for animal experiment :
1 Experiment human (+)and animal (+ ).
3. Experiment animal (+), human (-).
4. Animal (-), human (+)
Different metabolite, different sensitivities to
receptor, different anatomy and physiology,
disease condition or other disease, or enzyme
induction.

3.

POISON

1. Choose of poison :
- How to happen
- Self poisoning
- Attempted suicide
- Accidental poisoning
- Homicide poisoning
Time acute : vomit, diarrhoea, coma,
convulsive
3. Organ affected SSP, liver, heart, kidney
(carbon tetrachloride)
4. Chemical material some chemical
substance same characteristic toxic (alcohol,

3.2 Cause of poison :

- Enterococcus staphylococcus contamination
of food poison
- Faloidin from fungus
- Ichtyosarcotoksin from fish.
- Jengkol obstruct tubuli kidney hematuria
and anuri.

3. 3 Symptom and Diagnose of Poison :

-

Coma hypnotic,

Hypnotic coma tonus and muscle

reflection (exp. anaesthesia)
Anticholinergic midriasis, tachycardia, red
skin and fever
Coma different tolerance and sensitive a person.

BP Shock center vasomotor p/ bad

Cramp - stimulation

CNS (amphetamine)

- Medulla spinalis (Strychnine)

- Relation muscle-nerve ( insecticide
organophosphate)
Peristaltic intestines : consciousness III and IV is
loss.
Heart : digitalis, antidepressant trisiklik,
hydrocarbon chloride.
Others : barbiturate, hypnotic : bulla to skin.
3.4 Role of Laboratorium :
-

Blood Analysis

- Chromatography thin layer

- Chromatography gas
- High performance Liquid Chromatography.

3. 5 Toxicities Therapy:
Toxicities Pb, AS, HG, Cyanide, insecticide
organophosphate, insecticide karbamat,
morphine, warfarin.
In an emergency :
- Respiratory attack : respirometer
- Prevention of absorption much more :
Soap and water : zalf
Inhalation : move to fresh room

- laxative to increase peristaltic intestines

lack of absorption time.
- Carbon active absorbed the drug in
digestion and excretion through bile duct

Others action :
1. Water balancing and electrolyte along with
kidney fail.
2. Antibiotic for inflammation of the lungs
complication.
Others :
1. Transfusion
2. Dialysis peritoneal
3. Diuresis
4. Haemodialysis
5. Barbiturate, diazepam for cramp

Toxin and Therapy action

- Alcohol : vomit, delirium, depression CNS
R/ Symptom, coffee, emetic.
-Atropine : dry mouth, red skin and midriasis,
tachycardia.
R/ Milk, clean intestines with water. --Barbiturate/ fenobarbiturate : Reflex
decrease, respiratory depression, coma,
shock, meiosis.
R/ Coffee.

-Benzene : Inhalation and oral

vomit, headache, coma, central depression
and respiratory depression.
- INSECTISIDE
- Organophosphate group : DDT, diazinon,
malation and parathion.
Oral, inhalation, skin contact.
Vomit, diarhea, hypersalivasi,
bronkhokonstriksi, much perspiration,
meiosis, bradikardi (sometime tachykardi),
tBP , paralysis, respiratory depression.
R/ Clean respiratory tract
2 mg SA iv regain each 10-15 minute until
looks red face, hipersalivasi, tachykardi and

Group of Karbamat Kerbaril, Baygon

Idem
- Group of Organoklorin
Aldrin, DDT, Dieldrin, endrin, klordan, tiodan adn
toksafen.
Cramp tremor, coma paralysis
R/ Clean intestines with MgSO4 30 gram,
Phenobarbital 100-200 mg, diazepam iv 5-10 mg.

- Canfer
Cramp
R/ Symptom
Luminal 100-200 mg i. m
- CO
Headache, respiratory depression, coma and
shock
R/ Artificial respiration and O2
- Codeine

Vomit, headache, dry skin, cramp, coma, fibrilasi

ventrikel, heart function attack and kidney
R/ Symptom
- Marihuana

- Morphine = Codeine
- Drug reaction
Kinds of skin reaction, fever, angioneurotik udem,
serum reaction, anaphylactic reaction.
R/ 0,3 adrenalin 1% subkutan, antihistamine,
deksametazon
.