Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

CARCINOGENIC AND TERATOGENIC CHEMICAL SUBSTANCES

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Carcinogen - An agent which may produce cancer (uncontrolled cell growth), either
by itself or in conjunction with another substance
carcinogenic properties of
chemicals are identified from
(1) Human epidemiological studies
establishing relationships
between exposure to any given
chemical and cancer, and
(2) laboratory studies in experimental
animals

Caused by Chemicals,
radiation, and certain viruses

Most cancers are induced by many

synthetic or naturally occurring
chemicals, which include inorganic
substances, organics, hormones, and
solid-state materials

Cancer is a common condition and is thought to be most often due to environmental causes
rather than arising spontaneously. Important known associations with an increased risk of
cancer in humans include smoking (lung cancer), sexual promiscuity (cancer of the
cervix) and low-fibre diet (large bowel cancer).
A human carcinogen is a substance that induces cancer in humans.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Tumor or neoplasm is heritable altered autonomous growth of tissue,

composed of abnormal cells that grow more rapidly than the surrounding normal
cells
Neoplasm may be of two types, benign and malignant. While the former grows
much more slowly than the latter, and does not metastasize (spread) throughout the
body, malignant tumor or cancer grows rapidly and spreads throughout the body.

Neoplasms use the blood, oxygen, and nutrient supplies of other tissues and
organs affecting the normal function of bodys organs and tissues. Neoplasms
that continue to grow unabated and spread, as happens in malignancies,
ultimately lead to death

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Carcinogen - An agent which may produce cancer (uncontrolled cell growth), either
by itself or in conjunction with another substance

Caused by Chemicals,
radiation, and certain viruses

Chemical carcinogens
exert their effects after prolonged
exposure for years, often with a latent period
of several years

Miranda Adihimawati, M.Sc.

Universitas Islam Negeri Sunan Kalijaga

Carcinogen - An agent which may produce cancer (uncontrolled cell growth), either
by itself or in conjunction with another substance

Caused by Chemicals,
radiation, and certain viruses
Also, most carcinogens manifest a doseresponse relationships

Chemical carcinogens
exert their effects after prolonged
exposure for years, often with a latent period
of several years

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Carcinogen - An agent which may produce cancer (uncontrolled cell growth), either
by itself or in conjunction with another substance

Caused by Chemicals,
radiation, and certain viruses
Example: asbestos fibers have demonstrated long
latent periods, with the first signs of cancers appearing
2030 years after exposure

Chemical carcinogens
exert their effects after prolonged
exposure for years, often with a latent period
of several years

Universitas Islam Negeri Sunan Kalijaga

Example:

Miranda Adihimawati, M.Sc.

asbestos fibers have demonstrated long latent periods, with the first signs of cancers

appearing 2030 years after exposure

Mesothelioma is a rare and aggressive cancer diagnosed

in an estimated 3,000 Americans annually caused almost
exclusively by asbestos exposure
It involves the thin lining that surrounds organs in the chest
and abdomen and kills an American every 3.4 hours
Mesothelioma first was clinically mentioned in 1921,
describing as primary tumors of the pleura, the membrane
surrounding the lungs
In 1924, the first diagnosis of asbestosis a lung disease characterized by a scarring
caused by asbestos fibers. Asbestos exposure can also cause lung cancer

http://www.asbestos.com/asbestos/

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

The biochemical processes involved in carcinogenesis are not well understood. It is

known that many mutagens are also chemical carcinogens.

Therefore, the mutation of normal

cells exposed to chemical carcinogens can lead to the development of cancerous cells.

Mutation is a permanent change in the base sequence of the

deoxyribonucleic acid (DNA) involving alterations of a single gene, a block of
gene, or a whole chromosome

Carcinogenic chemicals may alter DNA to

form a type of cell that replicates itself, forming
cancerous tissue.
A chemical may interact with DNA through genetic mechanism, altering the structure or number in the chromosome, causing gene
mutation or duplication.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

MECHANISM OF CHEMICAL
CARCINOGENESIS
genotoxic carcinogens manifest their actions in three phases:
(1) initiation,
The routes of exposure, dose amount, absorption, and
(2) promotion, and
distribution of the chemical within the body as well as the
(3) progression
nature of the metabolic products.
The process of initiation by genotoxic carcinogens occurs when the chemical
reacts with the DNA molecule.

An electrophilic (electron-seeking) compound can bind covalently to certain

nucleophilic sites in DNA, forming a carcinogenDNA adduct.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

MECHANISM OF CHEMICAL
CARCINOGENESIS
genotoxic carcinogens manifest their actions in three phases:
(1) initiation,
The routes of exposure, dose amount, absorption, and
(2) promotion, and
distribution of the chemical within the body as well as the
(3) progression
nature of the metabolic products.
The process of initiation by genotoxic carcinogens occurs when the chemical
reacts with the DNA molecule.

Initiation is succeeded by a long phase of promotion

Gross tumors form during this long phase.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

MECHANISM OF CHEMICAL
CARCINOGENESIS
genotoxic carcinogens manifest their actions in three phases:
(1) initiation,
The routes of exposure, dose amount, absorption, and
(2) promotion, and
distribution of the chemical within the body as well as the
(3) progression
nature of the metabolic products.
Progression is the final phase of tumor growth after various substances of
neoplastic cells have emerged

At this stage, secondary metastatic deposits keep on

forming at increasing numbers of sites, with additional
mutational changes occurring

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Carcinogen - The following classes of chemicals are know to contain carcinogens:

polycyclic aromatic hydrocarbons
aromatic amines
N-nitroso compounds
azo dyes

Their chemical structures

are diverse, as are their biological effects
and the mode of action

alkylating agents
some naturally occurring compounds
various halogenated hydrocarbons, polychlorinated biphenyls (PCBs), dioxin,
barbitals, synthetic and endogenous hormones, and many substances that are
enzyme inducers

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Carcinogen - An agent which may produce cancer (uncontrolled cell growth), either
by itself or in conjunction with another substance

non-carcinogens
Known
carcinogens

suspected carcinogens

agents of undetermined
carcinogenicity

Suspect Carcinogen - An agent which is suspected of being a carcinogen based on

chemical structure, animal research studies, or mutagenicity studies.

The statutory requirements relate specifically to those agents which must be labelled
"carcinogenic - category 1" or "carcinogen - category 2" under the Chemicals (Hazard
Information and Packaging) Regulations 1993 (CHIP)

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Cancer staging is the process of determining how much cancer is in the body and where it is
located. Staging describes the severity of an individual's cancer based on the magnitude of
the original (primary) tumor as well as on the extent cancer has spread in the body.
There are four different types of staging:
Clinical Staging determines how much cancer there is based on the physical examination,
imaging tests, and biopsies of affected areas.
Pathologic Staging can only be determined from individual patients who have had
surgery to remove a tumor or explore the extent of the cancer. Pathologic staging
combines the results of both the clinical staging (physical exam, imaging test) with
surgical results.
Post-Therapy or Post-Neoadjuvant Therapy Staging determines how much cancer
remains after a patient is first treated with systemic (chemotherapy or hormone therapy)
and/or radiation therapy prior to their surgery or where no surgery is performed. This can
be assessed by clinical staging guidelines and/or pathologic staging guidelines.
Restaging is used to determine the extent of the disease if a cancer comes back after
treatment. Restaging helps determine the and the best treatment options for cancer that
has returned.
https://cancerstaging.org/references-tools/Pages/What-is-Cancer-Staging.aspx

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Teratogens Compounds that cause embryonic mortality or birth of offspring

with physical, mental, or developmental defects
Teratogens are chemical and physical agents that can cause birth defects and
mortality among newborns, malformations, growth retardation, and functional
disorders.
the most dangerous teratogenic effects have been shown by thalidomide

This drug, used in the past for the relief of morning sickness, caused phocomelia, a very rare type of
congenital malformation among newborn babies

Ingestion of thalidomide by pregnant mothers resulted in the births of thousands of

deformed babies with shortening or absence of limbs

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Teratogens are chemical and physical agents that can cause birth defects and
mortality among newborns, malformations, growth retardation, and functional
disorders.

Although most teratogens are chemical in

nature, ionizing radiation, nutritional imbalance,
and certain infections are also known
to be teratogenic to humans.

Most of the organogenesis occurs during the embryonic stage, with the cells undergoing intensive
differentiation, mobilization, and organization.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Teratogens are chemical and physical agents that can cause birth defects and
mortality among newborns, malformations, growth retardation, and functional
disorders.

Although most teratogens are chemical in

nature, ionizing radiation, nutritional imbalance,
and certain infections are also known
to be teratogenic to humans.

Teratogens may not cause morphologic defects in the fetal stage, during which growth and
functional maturation occur. However, they may induce functional abnormalities, such as central
nervous system deficiencies, which may not be detected at birth or shortly thereafter

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

Organic solvents, alcohols, pesticides, herbicides, azo dyes, heavy metals,

sulfonamides, antibiotics, and certain alkaloids

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

How teratogens act depends on their certain chemical properties. Thus, their
mode of action in humans and animals may involve many different mechanisms

Many teratogens can interfere with replication or transcription

of nucleic acid or RNA translation

Such effects can cause cell death or somatic mutation in the embryo

result in structural and functional defects

Therefore, the toxicants that produce reactive metabolites that react with nucleic acids can be potential teratogens.
If such metabolites are too unstable, they may be carcinogens,
but not teratogens

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

The mode of action of many teratogens is different and is not fully

understood.

The mechanism depends on several factors, such as bioactivation of toxicants,

the stability of toxicants or their reactive metabolites to reach the embryo, and
biotransformation or the detoxifying capability of the embryonic tissues.

Teratogenic effects of substances on test animals are evaluated from:

resorption (death of the conceptus),
fetal toxicity (reduced body weight),
aberrations (malformations), and
minor anomalies

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

All Laboratory use of carcinogens, mutagens and teratogens shall meet or

exceed the requirements and regulations of
the Occupational Safety and Health Administration (OSHA),
the U.S. Department of Energy (DOE),
the Environmental Protection Agency (EPA),
and the guidelines set by the American Conference of Governmental
Industrial Hygienists (ACGIH) and
the National Institute for Occupational Safety and Health (NIOSH)

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

General Laboratory Controls

A. To entrance to the area where the carcinogen, mutagen, or teratogen is being
used, shall be restricted to personnel directly involved in experimentation or
required services, and signs shall be posted at the entrances to the area.
B. Local ventilation in the form of fume hoods and close-capture systems shall be
available for any experiment that produces significant amounts of airborne gas,
vapor, or particulate. These systems shall be of the "once through" type; no
recirculation of exhaust air will be permitted.
C. Eating, drinking, tobacco or gum chewing, food storage, smoking, and
application of cosmetics shall be prohibited in the laboratory work area.
D. Mechanical pipetting aids shall be used for all pipetting procedures.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

General Laboratory Controls

E. Solid and liquid wastes shall be properly labeled and collected separately in nonpermeable containers and shall be disposed of through the Environmental
Restoration/Waste Management (ER/WM) Division.
F. Separate receptacles for non-contaminated broken glass shall be provided in all
laboratory work areas.
G. Hypodermic syringes shall be disposed of in disposal containers designed for
sharps.
H. Laboratory floor and bench-top surfaces shall be made of, or be covered with, a
non-permeable material such as stainless steel or polyethylene to facilitate cleanup of spilled materials.
I. Carcinogens, mutagens, and teratogens are also subject to all other applicable
policies in the Environment, Safety and Health (ES&H) Manual for flammable
liquids. Where a conflict occurs, the most stringent policy shall apply.

Universitas Islam Negeri Sunan Kalijaga

Miranda Adihimawati, M.Sc.

General Laboratory Controls

J. Safety-shower and eye-wash facilities shall be located within, or in close
proximity to, the laboratory.
K. All containers shall be clearly marked as to general hazard and complete
chemical contents.
L. Emergency action plans shall be included in the standard operating procedure.
M. The workplace shall only be exposed to the amount of material needed to
complete the project, and no quantity of material greater than what is needed
should be purchased. Excess chemicals and unusable equipment should be
disposed of once the project is completed through ER/WM.