Toksikologi Zat Kimia

Andriyanto, Drh, Msi

Perencanaan Hidup
Toxicology Concepts
 Risk
The likelihood of injury or
disease resulting from
exposure to a potential
hazard

Evaluation of risk
embodies all the basic
concepts of toxicology
The science of Toxicology helps people make
informed decisions and balance
RISKS vs. BENEFITS

The study found the

highest levels of AND Spinach.
pesticide residues in
peaches, apples,
pears.
 Exposure
Sources of exposure to
chemicals
Environmental,
including home and
school
Occupational
Therapeutic
Dietary
Accidental
 Exposure
In order for a chemical to produce a biological effect, it must first reach
a target individual (exposure pathway).
Then the chemical must reach a target site within the body
(toxicokinetics).
Toxicity is a function of the effective dose (how much) of a foreign
chemical (xenobiotic) at its target site, integrated over time (how long).
Individual factors such as body weight will influence the dose at the
target site

X =
 Exposure
Route of Exposure
The route (site) of exposure is an important
determinant of the ultimate dosedifferent routes
may result in different rates of absorption.
Dermal (skin)
Inhalation (lung)
Oral ingestion (Gastrointestinal)
Injection
The route of exposure may be important if there
are tissue-specific toxic responses.
Toxic effects may be local or systemic
 Exposure
Time of Exposure
How long an organism is
exposed to a chemical is
important
Duration and frequency
contribute to dose. Both
may alter toxic effects.
Acute Exposure = usually entails a single
exposure
Chronic Exposures = multiple exposures
over time (frequency)
 Dose
THE KEY CONCEPT in Toxicology

Father of Modern Toxicology

Paracelsus
1564

All things are poisonous, only the dose makes it

non-poisonous.
Dose alone determines toxicity
All chemicalssynthetic or naturalhave the
capacity
to be toxic
 Dose

All Interactions between

chemicals and biological systems follow a
Dose-Response Relationship
 Dose
Woman Dies after Water-drinking Contest: Water
Intoxication eyed in Hold Your Wee for a Wii contest Death

SACRAMENTO, CaliforniaA woman

who competed in a radio stations
contest to see how much water she
could drink without going to the
bathroom died of water intoxication,
the coroners office said Saturday.

Updated: 10:24 p.m. ET Jan 13, 2007

 Dose-Response Relationship
A key concept in Toxicology is the quantitative
relationship between the concentration of a
xenobiotic in the body and the magnitude of the
biological effect it produces.
The magnitude of the effect of a xenobiotic is
usually a function of the amount of xenobiotic to
which a person is exposed (i.e., The Dose Makes
the Poison).
In any given population, there will be a range of
sensitivities to a xenobiotic. It is extremely useful
to know what is the average sensitivity of a
population to a xenobiotic, and what the average
dose required to elicit a toxic response will be.
 Dose
The magnitude of the toxic response is
proportional to the concentration (how much) of
the chemical at the target site.
The concentration of a chemical at the target site
is proportional to the dose.
Four important processes control the amount of
a chemical that reaches the target site.

Absorption
Tissue distribution
Metabolism
Excretion
 Dose
Determines Whether a Chemical Will Be Beneficial or
Poisonous
Beneficial Dose Toxic Dose
Aspirin 300 1,000 mg 1,000 30,000 mg
Vitamin A 5000 units/day 50,000 units/day
Oxygen 20% (Air) 50 80% (Air)
Keracunan Zat Kimia (1)

Pursani Paridjo
M. Iskandar
Huda S D
 Referensi
Casarett and Doulls, 2003, Essential of Toxicology

Clark & Humprey, 1997, Veterinary Toxicology

Lu, C. F, 1995, Toksikologi Dasar (translasi Edy Nugroho)

Bartik & Piskac, 1981, Veterinary Toxicology

 Kata Kunci
Solvent (pelarut), Cairan kimia organik dengan:
a. Keragaman kemampuan lipofilik dan volatil
b. ukuran molekul kecil
c. polaritas rendah

Absorpsi zat kimia organik volatil (vapors) per inhalasi via paru
(alveol)

Pelarut diabsorbsi via GI s.d. kulit

Kebanyakan pelarut menyebabkan gangguan SSP

 Toxicology
Study of the adverse effect of xenobiotics/ chemical on
living systems

Racun/ poison: any agent capable of producing a

deleterious response in a biological system

Toksin: refers to toxic substances that are produced by

biological system

Toksikan: ~ by or by-products of anthropogenic (human)

activities
 Pendahuluan
Solvent Petroleum based (Naphthalene, Benzene)

Used for water insoluble material

Kelarutan (lipophilicty)
Penguapan (Volatility)

Klasifikasi : Struktur Kimia & Grup Fungsional

 Klasifikasi
Hidrokarbon alifatik- halocarbon (N-Heksan)
Hidrokarbon alifatik- berklor (kloroform)
Hidrokarbon aromatik (Benzen)
Alkohol
Ethers
Esters/ asetat
Amides/ Amines
Aldehid
Keton
 Paparan
Hampir semua organisme terpapar zat kimia
Gabungan beberapa senyawa, jarang tunggal
 Intoksikasi
Toksisitas bersifat additive, sinergis & antagonis

Bahaya beberapa solvent lebih tinggi

Seluruh solvent berpotensi toksik

Secara keseluruhan menginduksi narkose (neurologik)

dan iritasi kulit & membran mukosa

Beberapa karsinogen, hanya sedikit yg sudah

teridentifikasi
 Neurological Syndrome-Man
Painters synd, organic solvents synd, psychoorganic synd
& chronic solvent encephalopathy (CSE)

Abuse menginginkan efek sedasi, euphoria, audio &

visual halusinasi

Intoksikasi umumnya karena cemaran lingkungan via

evaporasi oleh Volatile Organic Compound (VOC)-
aerosol propellants, thinner, cleaner, dll
 Toksikokinetik - Absorpsi
Alveol & sal resp atas. Lipofilik PC (Partition Coeff)
Kenaikan Darah- Udara uptake meningkat

GI 100% efek sistemik

Kulit sistemik & lokal (diffusi pasif).

Laju absorpsi kulit tgt: konsentrasi, luas permukaan

terpapar, durasi, integritas& ketebalan str.korneum, MW
zat
 Distribusi
Hepatic first pass elimination

Pulmonary first pass elimination

GI tract vena porta eksresi via paru tidak masuk

arteri (jika solvent volatil dimetabolisme dengan baik)

Solvent lipofilik arteri berikatan dengan hidrofobik

sites (memb. Fosfolipid, kolesterol) depo di jaringan
adiposa
Tgt Blood Flow & kandungan lipidobese??
 Metabolisme & Eksresi
Biotransformasi
Modulasi toksisitas solven megubahnya
menjadi relatif larut air eliminasi/ eksresi
lebih banyak via urin dan atau empedu
(lemak)
Bioaktifasi solven metabolit reaktif
sitotoksik & mutagenik
 Populasi yang berpotensi terpapar
Faktor Endogen
Usia Anakan
Hewan tua
Genetik

Faktor Eksogen
Sitokrom P450 inhibitor & inducer
Aktifitas Fisik- olah raga- ventilasi alveolar
Diet- banyak isi GI absorpsi lebih lambat
 Hidrokarbon BerKlor
No Nama Zat Kegunaan Rute CNS - Uro Organ Metabolit Keterangan
Tox Neurologik genital Interna Tambahan

1 Trichloroethyele Pelarut oli I, O, Depresan, Kanker Kanker hati, TCOH to Karsinogenik,

(TCE) D Myeloma Prostat paru & ginjal P450 Hodgkins

2 Tetrachloroethyl Dry cleaner, I, O - - Esofagus, TCAcetic Rokok& minum

ene (PERC) Stainer ginjal to P450 alkohol

3 Methylene Preparasi I - - Gangguan - Efek sistemik

Chlorid (MC) makanan, ringan & terbatas - low
aerosol reversibel carsinogenitas
propellan

4 Carbon - O, IV - - Hepatoseluler - Hepatotoxin

Tetraklorida injury klasik, manusia
(CCl4) ginjal

5 Chloroform Refrigerant O Sub - Hepato & Phosgene Carcinogen

(CHCl3) Anesthetic nephro to lipid (rodent), probable
necrosis (man)
 Hidrokarbon Aromatik
06 Benzene BBM I - - Hematopoietik Benzene perokok (benzene
. (tanpa Pb) (anemia, to GSH, level 6-10x)
leukopenia, DNA,RNA Myelodisplasia
trombositope, acute
Marrow aplasia myelogenous
leukaemia (AML)

07 Toluene Cat, lem, I, O Depresi, - Depresi - Target utama

. (alkylbenzene) thinners, nystagmus, respirasi CNS
campuran atropi (toluene &
bensin cerebral alkilbenzen),
exhaled
unchanged

08 Xylene & Komponen I Depresi - Hati, ginjal Xylene Karsinogenik

. Ethylbenzene utama to (ethyllbenzen &
bensin & P450 styrene)
BBM
 Alkohol
9. Alkohol - Industri, O Alcoholism- - Nekrosis Asetaldehid Fetal Alcohol
Ethanol farmasi, retardasi hati, dehidrognase Syndrome (FAS)-
minuman mental-FAS Cardiomyo (ALDH) maternal alkohol
pathy, saat hamil,
microcephaly,

ALDH kaukasus
>> Asia

10. Methanol Pembuatan I, O Iritasi - Formic - Gangguan visual

formalin, sensori, acidemia, (per os) retina,
BBM narcosis (I), okuler
koma toxicity
 Glikols
11. Glikol- Kriopreservatif, O, Hypocalcemia - Cardiac Asam Metabolik asidosis
Ethylene cairan hidrolik, D (kelasi kristal failure, glikolik (akumulasi asam
Glikol tinta CaOxalat) pulmonary
glikolik),
edema,
nekrosis kristal kelat kapiler
ginjal otak& ginjal

12. Propylene Pelarut, O, Depresi, - Hemolisis- Lactal- FDA approved,

Glikol (PG) pendingin, D encephalopathy Lactic dehyde- toksisitas
antifreeze acidosis laktat
jika ekstrim tinggi

13. Glikol s.d.a O Hydrocephalus, - Hemolisis 2 Methoxy- Toksisitas utama pada

Ethers spina bifida Ethanol reproduksi,
(defek neural
pertumbuhkembangan
tube), cleft lip
(sumbing) dan hematopoietik,
Sperma-toxicity,
atrophy testis,
abnormal akrosom
 BBM & BBM Aditif
BBM otomotif
Hydrokarbon rantai panjang (C4-C12)
Karsinogen (benzene, 1,3 butadiene)
Occupational Toxicities encephalopathy
Oral nausea, vomit, diare
Inhalasi rusak epitel pulmoner, edema, pneumonia

Methyl Tertier- Butil Ether-MTBE (Octane booster)

Menyempurnakan pembakaran, reduksi emisi polusi
Simptom akut: iritasi mata, hidung, nausea, batuk (mukosa surface)
Grup C human carcinogen (tumor testis, lymphoma, adenoma hati)
 Pengaturan
Occupational Safety& Health Administration
(OSHA)

Permissible Exposure Limits (PELs) 100

pelarut

Threshold Limit Values (TLVs), published by

American Conference of Governmental
Industrial Hygiene (ACGIH)
Sekian & Trims