TOKSIKOLOGI

DASAR

Dr. dr. M. Yulis Hamidy, M.Kes., M.Pd.Ked

EFEK ALKOHOL PRENATAL
EFEK TOKSIK TIMBAL
EFEK TOKSIK MERKURI
DEFINISI TOKSIKOLOGI
• Toxicology has been called the science of
poisons
• “Toxicology is the study of the adverse
effects of chemical, physical or biological
agents on living organisms and the
ecosystem, including the prevention and
amelioration of such adverse effects”
(Hodgson et al, 2005).
• “Toxicology. . . is the science that studies the
harmful effects of drugs, environmental
contaminants, and naturally occurring
substances found in food, water, air and
soil”.
What is the purpose of a
presentation on toxicology?
An understanding of some basic
principles of toxicology will be
helpful during our safety & health
PERANAN TOKSIKOLOGI
• Memperbaiki kesehatan manusia, hewan
dan lingkungan
• Menjamin keamanan dari suatu obat,
bahan kimia yang terdapat di rumah
tangga dan industri
• Menilai efek-efek yang membahayakan
dan menentukan dosis yang dapat
menyebabkan efek tersebut (penilaian
risiko)
• Menjelaskan mekanisme suatu substansi
dalam menyebabkan kerusakan,
sehingga dapat digunakan sebagai dasar
dalam memberikan penatalaksanaan
pada kasus keracunan
CAKUPAN TOKSIKOLOGI
 TOKSISITAS
• “Toxicity is the adverse end product of a
series of events that is initiated by exposure
to chemical, physical or biological agents”
(Hodgson et al, 2005)
• “Toksisitas adalah kemampuan bahan kimia
untuk menyebabkan kerusakan (injury)”
(Plaa, 2001)
• “The dose makes the poison. Toxicology is
part of the solution” (Paracelsus)
 TOKSISITAS
• Akut vs kronis
• Ringan vs berat
• Reversibel vs ireversibel
 BAHAYA (HAZARD)
• Kemungkinan kejadian kerusakan
pada situasi atau tempat tertentu
• Kondisi penggunaan dan kondisi
paparan menjadi pertimbangan
utama
• Perlu diketahui
• sifat bawaan toksisitas unsur (aspek
kualitatif)
• besar paparan yang diterima individu
(aspek kuantitatif)
 TOKSIKOKINETIKA
Paparan zat kimia
- Inhalasi Absorpsi
- Ingesti
- Kontak
- Parenteral

Distribusi Eliminasi

Organ target Efek toksik

PENILAIAN TOKSISITAS AKUT
• Efek toksik yang terjadi setelah paparan
tunggal dari suatu zat kimia
• Diukur pada hewan coba seperti tikus
atau mencit
• Lethal dose 50 (LD50) adalah jumlah zat
kimia yang diingesti, diinjeksi, atau
diaplikasikan pada kulit hewan coba yang
menyebabkan kematian pada 50%
populasi (mg/kgBB)
• Lethal concentration 50 (LC50) yaitu
konsentrasi bahan kimia volatil yang
terdapat di udara yang menyebabkan
kematian pada 50% populasi (ppm atau
mg/m3) dalam periode waktu tertentu
• LDlo dan LClo, yaitu dosis atau
konsentrasi terendah yang dapat
menyebabkan kematian hewan coba
PENILAIAN TOKSISITAS KRONIS

• Efek toksik kronis seperti kerusakan organ,

kanker, gangguan reproduksi dapat diteliti
pada manusia melalui penelitian
epidemiologi, hewan coba, ataupun
penelitian pada level molekuler
• Zat-zat yang teridentifikasi dapat
menyebabkan efek kronis harus ditangani
dengan baik untuk meminimalisasi terjadinya
paparan zat tersebut
How are Toxicological Data Obtained?
Toxicological data are often obtained from laboratory
studies, conducted in animals (mice, rats). Although it
is preferable to have data from humans, this may not
be possible. In some cases, human data have been
obtained from accidents, suicides, poisonings, or from
epidemiology studies.
KLASIFIKASI TOKSIKOLOGI

• Toksikologi kerja
• Toksikologi lingkungan
• Ekotoksikologi
TOKSIKOLOGI KERJA
• Berhubungan dengan berbagai unsur
kimia di tempat kerja
• Toksikologi kerja terutama ditekankan
pada:
• identifikasi bahan berbahaya
• penjelasan cara penggunaan
yang aman
• pencegahan absorpsi dalam
jumlah yang berbahaya
PEDOMAN PENILAIAN PAPARAN

• Nilai ambang batas (TLV = threshold

limit values) yang dinyatakan
dengan bagian per mili (part per
million, ppm) atau miligram per
meter kubik (mg/m3) yang
mencakup berbagai kondisi paparan
PEDOMAN PENILAIAN PAPARAN

• Threshold Limit Values-Time

Weighted Average (TLV-TWA), yaitu
konsentrasi untuk jam kerja normal
8 jam per hari kerja atau 40 jam
per minggu yang memungkinkan
para pekerja berulang kali terpapar
tanpa efek membahayakan
PEDOMAN PENILAIAN PAPARAN

• Threshold Limit Values-Short

Time Exposure Limit (TLV-STEL),
yaitu konsentrasi maksimum yang
tidak boleh dilampaui kapanpun
selama 15 menit periode paparan
PEDOMAN PENILAIAN PAPARAN

• Threshold Limit Values-Ceiling

(TLV-C), yaitu konsentrasi tidak
boleh dilampaui meskipun secara
singkat
TOKSIKOLOGI LINGKUNGAN

• Mengkaji dampak unsur kimia berbahaya

dalam bentuk polutan terhadap
lingkungan dan makhluk hidup
• Istilah lingkungan mencakup seluruh
sekeliling organisme, terutama udara,
tanah dan air
• Polutan adalah unsur yang terdapat di
lingkungan, minimal sebagai bagian dari
aktivitas manusia yang berdampak
membahayakan organisme hidup
• Pedoman penilaian paparan menggunakan
Acceptable Daily Intake (ADI) yang
dinyatakan dengan miligram per kilogram
berat badan per hari (mg/kgBB/hari)
 EKOTOKSIKOLOGI
• Perluasan toksikologi lingkungan
• Mempelajari efek toksik bahan kimia
dan fisik terhadap makhluk hidup,
khususnya pada populasi dan
komunitas dalam ekosistem tertentu
• Mencakup jalur transfer dan interaksi
bahan tersebut dalam lingkungan
 What is Meant by the Term,
“Extrapolation”, as it is Used in Toxicology?
The term, extrapolation, often indicates that
the risk (of a particular adverse health effect)
has been estimated for humans based upon
responses from animals.
Toxicological Data
 How Does a Chemical “ENTER”
the Body?
A chemical may “enter” the body (= route of entry)
through the respiratory tract (inhalation), the skin
(dermal absorption), and the gastrointestinal tract
(ingestion). It is possible for a chemical to enter the
body through >1 site, and at the same time!
Can More Than One Chemical “ENTER”
the Body at the Same Time?

When you are exposed to >1

chemical at a time, there may be
interactions between these
chemicals once they enter the body.
The greatest concern is potential
synergism --- when the effect of
exposure to 2 or more chemicals is
much greater than that expected for
each chemical alone.
 Where Does a Chemical “GO” After
Entering the Body?

After a chemical enters the

body, it will pass into the
bloodstream and may be
distributed throughout the
entire body. Thus, a chemical
may reach many important
organ systems (ex: nervous
system, kidneys, reproductive
organs) in your body.
 How Does the Body Try to “DEFEND”
Itself Against Chemicals?

The body generally tries to

“change” a more toxic, fat-loving
chemical into a less toxic, water-
loving chemical. This process is
often called metabolism or
biotransformation. Our liver is
important for helping to make
this “change”, thus creating the
metabolites.
 How Does the Body Try to “RID”
Itself of a Chemical?
The body generally tries to “rid” itself of a
chemical and/or its metabolites through the urine
(kidneys involved), feces (liver involved), and
exhaled air (lungs involved). This process is often
called excretion or elimination.
What May Occur if the Body Fails to “RID”
Itself of a Chemical?
If the body fails to “rid” itself of a chemical and/or
its metabolites, storage may occur. For example,
lead (Pb) can be stored in bones.
What May Occur if the Body Fails to “RID”
Itself of a Chemical?
If the body fails to “rid” itself of a chemical and/or
its metabolites, adverse health effects may occur
at 1 or more sites. These affected sites are known
as target organs.
 What are Some of the Adverse Health
Effects That Could Occur in Human?

Because of the wide variety of chemicals used in

mining, there are many adverse health effects that
may occur. Some possible serious effects of
chemical exposure(s) include: death, cancer,
inability to have children, blindness, skin burns,
nerve degeneration, and permanent damage of
vital organs such as the lungs, liver, and kidneys.
 Can an Adverse Health Effect Occur
After a Single Exposure to a Chemical?

An adverse health effect can

occur after a single, brief (short-
term) exposure. This type of
exposure is often described as
acute. And, the effect(s) may be
permanent (irreversible).
 Can an Adverse Health Effect Occur After
Repeated Exposures to a Chemical?
An adverse health effect can occur after repeated
exposures to a chemical, over a prolonged period of
time. This type of exposure is often described as
chronic (long-term), and generally occurs at lower
concentrations (doses) than those needed to
produce an acute effect(s). Again, the effect(s) may
be permanent (irreversible).
 If There is Exposure to a Chemical Now,
When Might an Adverse Health Effect Occur?

An adverse health effect can occur at any time

(immediate and/or delayed) after exposure to a
chemical.
 How Might We Realize That We Have
Been Exposed to a Chemical?
We may experience a variety of signs and
symptoms of exposure to a chemical. We may
also become aware of a chemical exposure during
discussions with their doctors or during
routine physical examinations.
Air sampling, complemented
by biological monitoring, may
help to demonstrate current
workplace exposures.
 How Much of a Chemical is
“TOXIC”?
In toxicology, it is often said that “only
the dose makes the poison”. This
means that any chemical (substance)
can produce adverse health effects. It
is only a question of “how much?” You
are more likely to experience an
adverse health effect as the level of
exposure increases and the severity of
the effect is also likely to increase. This
is often described as the dose-
response or concentration-response
relationship.
 Are Some Chemicals “WORSE”
Than Others?
Comparisons may be regarding the toxicity of 2 or
more chemicals (= relative potency). Indeed, 1
chemical may be more “toxic” than another. When
conducting such comparisons, the same
toxicological endpoint must be examined. For
example, 2 or more chemicals may be compared
with one another on the basis of their ability either
to cause death or to produce cancer.

≠ ≠
INDIKATOR PENILAIAN KEAMANAN
SUATU ZAT KIMIA
• Data toksisitas akut dan subkronis yang
didapatkan melalui penelitian pada hewan
coba ekstrapolasi
• No Effect Level (NEL) atau No Observed
Effect Level (NOEL), yaitu “jumlah atau
konsentrasi suatu zat kimia yang ditemukan
melalui penelitian atau observasi yang tidak
menimbulkan kelainan buruk, perubahan
morfologi atau fungsi organ, pertumbuhan,
perkembangan, maupun mengurangi lama
hidup hewan coba”
INDIKATOR PENILAIAN KEAMANAN
SUATU ZAT KIMIA
• Acceptable Daily Intake (ADI), yaitu
“dosis suatu zat kimia terbesar yang
dinyatakan dalam satuan mg/kgBB/hari
yang dapat diberikan setiap hari seumur
hidup, dan diperkirakan tidak
menimbulkan efek kesehatan yang buruk
pada manusia, berdasarkan pengetahuan
yang ada pada waktu itu”
• ADI merupakan batas konsumsi harian
sehingga semakin kecil dikonsumsi tentu
akan lebih terjamin keamanannya. Zat
kimia yang diakumulasi di dalam tubuh
harus sudah diekskresi dalam 24 jam

• ADI= NEL mg/kgBB/hari

100
 INDIKATOR PENILAIAN KEAMANAN
SUATU ZAT KIMIA DALAM MAKANAN
• Untuk zat kimia yang dikandung oleh suatu
makanan, perlu diperhitungkan berapa konsentrasi
zat kimia tersebut diperbolehkan berada dalam
makanan yang disebut Maximal Permissible
Concentration (MPC)

MPC (ppm) = ADI x Berat Badan (kg)

Faktor makanan (kg)

Faktor makanan adalah konsumsi rata-rata suatu

makanan tertentu dalam kg/orang/hari
PREVENTION AND TREATMENT
OF POISONING
• Many acute poisonings from drugs could be
prevented if physicians provided common-sense
instructions about the storage of drugs and other
chemicals
• For clinical purposes, all toxic agents can be divided
into two classes: those for which a specific
treatment or antidote exists and those for which
there is no specific treatment.
• For the vast majority of drugs and other chemicals,
there is no specific treatment; symptomatic medical
care that supports vital functions is the only strategy
PREVENTION AND TREATMENT
OF POISONING
• Supportive therapy is the mainstay of the treatment
of drug poisoning.
• The adage, "Treat the patient, not the poison,"
remains the most basic and important principle of
clinical toxicology.
• Maintenance of respiration and circulation takes
precedence.
• Serial measurement and charting of vital signs and
important reflexes help to judge the progress of
intoxication, response to therapy, and need for
additional treatment.
• This monitoring usually requires hospitalization.
 Prevention of Further
Absorption of Poison
• Emesis
• Vomiting can be induced mechanically by
stroking the posterior pharynx
• Ipecac
• Syrup of ipecac is available in 0.5- and 1-fluid ounce
containers (approximately 15 and 30 ml), which may
be purchased without prescription.
• The drug can be given orally, but it takes 15 to 30
minutes to produce emesis
• The oral dose is 15 ml in children from 6 months to 12
years of age and 30 ml in older children and adults.
• Because emesis may not occur when the stomach is
empty, administration of ipecac should be followed by
a drink of water
 Prevention of Further
Absorption of Poison
• Apomorphine
• Apomorphine stimulates the CTZ and causes emesis.
• Apomorphine is not effective orally and must be given
parenterally, usually by the subcutaneous route, 6 mg
for adults and 0.06 mg/kg for children.
• However, this can be an advantage over ipecac in that
it can be administered to an uncooperative patient and
produces vomiting in 3 to 5 minutes.
• Because apomorphine is a respiratory depressant, it
should not be used if the patient has been poisoned by
a CNS depressant or if the patient's respiration is slow
and labored.
 Prevention of Further
Absorption of Poison
• GASTRIC LAVAGE
• Gastric lavage is accomplished by inserting a
tube into the stomach and washing the stomach
with water, normal saline, or one-half normal
saline to remove the unabsorbed poison.
• CHEMICAL ADSORPTION
• Activated charcoal avidly adsorbs drugs and
chemicals on the surfaces of the charcoal
particles, thereby preventing absorption and
toxicity
 Prevention of Further
Absorption of Poison
• CHEMICAL INACTIVATION
• Antidotes can change the chemical nature of a
poison by rendering it less toxic or preventing its
absorption.
• PURGATION
• The rationale for using an osmotic cathartic is to
minimize absorption by hastening the passage
of the toxicant through the gastrointestinal tract.
 Prevention of Further
Absorption of Poison
• INHALATION AND DERMAL EXPOSURE TO
POISONS
• When a poison has been inhaled, the first
priority is to remove the patient from the source
of exposure.
• Similarly, if the skin has had contact with a
poison, it should be washed thoroughly with
water.
• Contaminated clothing should be removed.
• Initial treatment of all types of chemical injuries
to the eye must be rapid; thorough irrigation of
the eye with water for 15 minutes should be
performed immediately.
Enhanced Elimination of the
Poison
• BIOTRANSFORMATION
• BILIARY EXCRETION
• URINARY EXCRETION
• DIALYSIS
• ANTAGONISM OR CHEMICAL INACTIVATION OF
AN ABSORBED POISON