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Mohammad Aneesul Mehmood
Industrial and agricultural activities, in the last 50 years,
have caused the significant increase in the concentration
of toxic pollutants in environment :
 Polycyclic aromatic hydrocarbons (PAHs),
 Polychlorinated biphenyls (PCBs)
 Chlorophenols
 Nitrophenols
 Benzene,ethylbenzene, toluene and xylene( BTEX),
 Organic solvents.
Most of these substances are mutagenic and
carcinogenic.
Environmental pollution of air, water and soil with
carcinogenic chemicals accounts for >55% of all cancers.
(IARC/WHO, 2013).
INTRODUCTION
 Cancer refers to a number of diseases
characterized by uncontrolled growth and
spread of abnormal cells.
 Carcinogenic effects of chemicals may be delayed for
as long as 30 years.
 Other carcinogens produce more immediate effects.
 Most carcinogens are unreactive or secondary
carcinogens but are converted to primary carcinogens
in the body.
 Numerous factors, such as heredity, affect the
susceptibilities of different individuals to cancer-
causing agents.
(Lancet, 2005)
Cont.…
 Cancer can affect almost anyone at anytime in their lives.
 Cancer can occur in almost any place in the body: Lung, Skin,
Breast, Prostate, Colon, and even the Blood (Leukemia)
 In December 2012 list by IARC, 328 substances
either known to cause or suspected of causing
cancer were identified.
Carcinogens
A carcinogen is a substance or agent known to
cause cancer or produces an increase in
incidence of cancer in animals or humans.
Carcinogens may be chemical substances;
physical agents, UV radiation; or biological
agents, such as certain viruses and bacteria.
A carcinogen may be the initiator — the agent
that alters or damages DNA, the basic coding
system of cells.
It may also be promoter — encouraging out-of-
control cell growth. (Gurr. et,al 2001)
Cancer is a Global Concern
World Health Organization
estimates that 80 per cent of
cancers are caused by
occupational or environmental
factors, including exposure to
hazardous chemicals and
radiations.
(WHO, 2012 http://www.who.int/)
Cont..
• There were an estimated 14.1 million cancer cases
around the world in 2012, of these 7.4 million cases
were in men and 6.7 million in women. This number is
expected to increase to 24 million by 2035 due to
alarming increase in environmental pollution.
• Lung cancer was the most common cancer worldwide
contributing 13% of the total number of new cases
diagnosed in 2012.
• Breast cancer (women only) was the second most
common cancer with nearly 1.7 million new cases in
2012.
• Colorectal cancer was the third most common cancer
with nearly 1.4 million new cases in 2012.
(IARC, 2013)
Entry of Carcinogen into Human Body
Ecokinetic properties of a pollutant
ENVIRONMENT
Pollutant
released into
environment
Transport, Photochemical
reaction, Adsorption,
Sedimentation
Sediment
SINK
Biokinetic properties of a pollutant
ORGANISM
BIOACCUMULATION
POLLUTANT,
DOSE DISTRIBUTION
METABOLISATION
MetaboliteExcretion of
compound
Metabolite
Compound
RISK = Hazard x
Exposure
Xenobiotics, Carcinogens, Environmental Chemicals.
Reactive metabolites, Epoxides, carbonium ions,
Quinines, alkyl halides.
TOXICITY
DNA damage
Water-soluble conjugate
detoxificationbinding
excretion Bile, urinecancer DNA repair
Fate of a carcinogen
Acquired environmental factors
chemicals ,radiation ,viruses
Changes in genome
of somatic cells
Activation of growth
promoting oncogenes
Inactivation of cancer
suppressor genes
Expression all altered gene products
and loss of regular gene products
MALIGNANT NEOPLASM
Genetic factors
Mutation
A change in the DNA
molecule
Process which
produces changes in
the DNA that may be
inherited.
Mutations in certain
genes could lead to
malignant
transformation of the
cell.
Many mutagens are
supposed to be
carcinogenic.
Metabolic activation of mutagens
PROMUTAGEN
ACTIVE
(ULTIMATE)
MUTAGEN
DNA ADDUCT (OR
OTHER CHEMICAL
MODIFICATION OF
DNA BASES)
MUTATION
enzymes
metabolic
activation
TUMOR
Carcinogens in Environment
• Chemicals (different pollutants)
 Alkylating agents
 Aromatic hydrocarbons (e.g.
benzo(a)pyrene)
 SMOKE
Main problem is due to cigarette
smoking
• Physical (ionizing
radiation, UV-radiation)
• Biological (viruses,
transposable elements)
(Yoo,Y.D 2012)
Cigarette Smoking• Cigarettes are smoked by over 1.1 billion
people. While smoking rates have leveled
off or declined in developed nations, in
developing nations tobacco consumption
continues to rise at a rate of around 3.4%
per annum.
• Worldwide, tobacco use causes more than 5
million deaths per year, and current trends
show that tobacco use will cause more than
8 million deaths annually by 2030 due to its
carcinogenic nature.
• In India, 96 cigarettes are consumed by per
adult per year.
(Federal Trade Commission Cigarette Report for 2013, Washington)
Benzo(a)pyrene (PAHs)
• Polycyclic aromatic hydrocarbon.
• Carcinogenic activity confirmed.
• A product of combustion processes (e.g.
tobacco smoking)
• A metabolic product binds to DNA →
adduct (a compound that results from
addition).
• Presence of adduct can cause mutation
and ultimately to cancer.
Metabolic
conversion
binds to
DNA
BaP – guanin adduct (Ramaswamy et al. 2002)
International Cancer Incidence
• Lung cancer is most common cancer
worldwide - 1.2 million new cases annually.
• Colorectal - 940,000
• Stomach - 870,000
• Liver - 560,000
• Cervical - 470,000
• Esophageal - 410,000
• Head and neck - 390,000
• Bladder - 330,000
• Leukemia - 250,000
• Pancreatic – 216,000
• Kidney – 190,000
• Nervous System – 175,000
• Pharynx – 65,000 (WHO, 2012)
International Research Tracking
Down Carcinogenic Substances
International
agencies such as the
UN’s International
Agency for Research
on Cancer (IARC),
are continually
updating lists of
known and
suspected
carcinogens.
Carcinogens: IARC
• Group 1: The agent (mixture) is carcinogenic to
humans, e.g. Asbestos, inorganic Arsenic etc.
• Group 2A: The agent (mixture) probably
carcinogenic, e.g. Vinyl chloride, Radon etc.
• Group 2B: The agent (mixture) possibly
carcinogenic, e.g. Acryl amide, Ethyl di bromide.
• Group 3: The agent (mixture or exposure
circumstance) is not classifiable as to its
carcinogenicity to humans, e.g. Dichloro benzene.
• Group 4: The agent (mixture) probably not
carcinogenic, e.g. Trichloroethane, Urethane.
Carcinogenic effect of Arsenic
 The compounds generally are not mutagenic, but may
inhibit enzyme function and induce gene amplification and
expression. Inorganic arsenic induces chromosomal
aberrations and sister chromatid exchange. (Snow et, al 2002)
 In vitro studies indicate that direct oxidative damage of
arsenic or its metabolites may play a role in cytotoxicity and
pulmonary DNA single-strand breaks. (Yamanaka, 2009)
 Chronic inhalation of arsenicals by PVC plant workers has
been found associated with lung cancer and angiosarcoma
(a rare form of liver cancer) [Falk et al. 2001]
 According to IARC and NRC, the association between chronic
arsenic exposure and cancer is strongest for skin, lung,
bladder, Liver (angiosarcoma) and kidney. [IARC 2004; NRC,
2000].
Chromium
• Occupational exposure to Cr(VI) compounds in a number of
industries has been associated with increased risk of
respiratory system cancers. [ATSDR 2000].
• The first epidemiological study of chromate production
workers in the United States that demonstrated an
association with lung cancer was conducted with 1,445
workers in seven plants engaged in the extraction of
chromates from ore from 1930 to 1947. The percentage
death due to cancer of the respiratory system was 21.8
[Machle and Gregorius 1948]
• Studies of workers in the chromium pigment, chrome-plating,
and ferrochromium industries showed a statistically
significant association between worker exposure to Cr(VI)
and lung cancer [Davies 1984].
Cadmium
• Cadmium’s toxicity primarily affects the lungs and
kidneys, with secondary effects on the skeletal system.
• There is sufficient evidence that cadmium metal and a
number of cadmium compounds, such as cadmium
chloride, oxide, sulfate, and sulfide, are carcinogenic in
animals and even to humans. Increased rates of
testicular, prostate, and lung cancer in animals have
been reported. (Sahmoun et al., 2010)
• Occupational studies have suggested possible
associations between chronic exposure to cadmium,
particularly cadmium oxide, and cancers of the lung,
prostate, and genitourinary system such as kidney
cancer. The strongest evidence for a linkage between
occupational exposure to cadmium and cancer is that of
lung cancer. (Sorhan and Esmen 2004)
Persistent Organic Pollutants
Persistent Organic Pollutants
(POPs) are chemical substances
that persist in the environment,
bioaccumulate through the food
web, and pose a risk of causing
adverse effects not only on
environment but also induce
cancer in test animals and human
beings.
(Sawada,N. 2003)
Dioxin
 Belong to the “dirty dozen” - a group of dangerous chemicals known as
persistent organic pollutants.
 In terms of dioxin release into the environment, uncontrolled waste
incinerators (solid waste and hospital waste) are often the worst culprits,
due to incomplete burning.
 Lipophilic in nature, i.e. absorbed by fat tissue.
 Their half-life in the body is estimated to be seven to eleven years.
 Some 419 types of dioxin-related compounds have been identified but only
about 30 of these are considered to have significant carcinogenic effects.
 Large amounts of dioxins were released in a serious accident at a chemical
factory in Seveso, Italy, in 1976. A cloud of toxic chemicals, including 2,3,7,8-
Tetrachlorodibenzo-p-dioxin, or TCDD, was released into the air and
eventually contaminated an area of 15 square kilometres where 37 000
people lived and contaminated almost all crops in their fields and about
10% of the population were reported to have carcinogenic effects.
(WHO,2011)
 Women exposed to TCDD in the Seveso accident in 1976 had abortions
because of fears of ill effects. The foetuses had higher levels of chromosome
aberrations (Tenchini et al., 1983)
 There is evidence that dioxins and furans cross the placenta more readily.
(Krowke et al.,1990)
Condition Selected exposures Selected occupations
Lung Asbestos
Chromium
Coal tar, pitch
Construction trades
Welding, plating
Steel working
Liver Vinyl chloride Plastics mfg.
Bladder Benzidine Plastics and chemical
manufacturing
Blood (leukemia) Benzene Benzene mfg., laboratories
Cancer Associated with Occupational
Exposure
(Stark, J. 2009)
Asbestosis
• Two types of fibers
 Serpentine
 Amphibole: Mainly responsible for lung cancer (thin and
straight) deeply penetrate into lungs, causes inflammatory
reaction lead to formation of fibrous mass which is visible
microscopically.
Ozone Depletion
UV rays
Can cause skin cancers: melanoma,
squamous cell carcinoma
(epidermis), and basal cell
(subcutis) carcinoma
It is capable to damage DNA
With extensive exposure to
sunlight, the repair system is
overwhelmed skin cancer
They cause mutations in TP53 gene
(Benn,J 2005)
Melanoma
• Melanoma is a cancer that develops in pigment cells called
melanocytes.
• Melanoma can be more serious than the other forms of skin
cancer, because it spreads to other parts of the body at a
very fast rate and cause serious illness and death.
• The incidence of both non-melanoma and melanoma skin
cancers has been increasing over the past decades.
Currently, between 2 and 3 million non-melanoma skin
cancers and 132,000 melanoma skin cancers occur globally
each year.
• It is estimated that a 10 per cent decrease in ozone levels
will result in an additional 300,000 non-melanoma and
4,500 melanoma skin cancer cases..
(WHO 2013)
Melanin
Melanin functions as a broad band UV
absorbent,
Has antioxidant and
Radical scavenging properties.
Many epidemiological studies have shown a
lower incidence for skin cancer in
individuals with darker skin compared to
those with fair skin.
(Brenner et al 2010)
Trichloroethylene
• The chemical compound trichloroethylene is a
chlorinated hydrocarbon commonly used as an
industrial solvent in dry clean industry.
• A recent analysis by USA EPA (2010) of available
epidemiological studies reports trichloroethylene
exposure to be associated with several types of
cancers in humans, especially kidney, liver, cervix,
and lymphatic system.
• A meta-analysis of these studies found that
occupational exposure to TCE was associated with
excess incidences of liver cancer, kidney cancer,
and multiple myeloma, with the strongest
evidence for the first three cancers
(Wartenberg, Reyner et al. 2000)
Microbial Carcinogens
• Salmonella typhi has been linked to
gallbladder cancer .
• Sources: sewage overflows, sewage
systems that are not working properly,
polluted storm water runoff, and
agricultural runoff and solid waste dump
sites.
• Byproducts, or impact of chronic
inflammation due to microbial infection,
may also be linked to oral cancers.
(Meyers et, al 2011)
• Chernobyl : An area of 1,00,000 sq km is
UNHABITABLE for 20,000 years. FOREVER.
Nuclear Radiations!
Date: 26 April 1986
Plant Capacity: 900 MW
40 Years Old Uranium Mines in
Jaduguda, Jharkhand (1962-2002)
Impact of Nuclear Radiation on Humans
Cancer in the next 20 to 60 years
Deformed babies - FOREVER!
(http://www.nrc.gov/)
After Chernobyl Nuclear Disaster 1986
(New York Academy of Sciences 2003)
After American Bombing in Iraq Depleted Uranium (DU)
Bombs made out of the Waste from Uranium Enrichment
(http://rense.com/general56/dep.htm)
Semey: USSR’s Nuclear Testing Site During Cold War
(http://www.coldwar.org/articles/40s/soviet_atomic_bomb_test.asp)
Postulated Mechanisms of
Pesticide Carcinogenicity
Mechanism Pesticide Examples
Genotoxicity Captan, Endosulfan
Tumor promotion Organochlorines
Hormonal action Atrazine, ziram
Immunotoxicity Aldicarb, 2,4-D
Peroxisome proliferation 2,4-D, 2,4,5-T
Zahm SH, et al. 2007
43
 By breathing air near where it has been
sprayed.
 Drinking water contaminated directly or
through run-offs.
 Being in contact with contaminated soil.
 Eating contaminated food.
 Smoking cigarettes made from endosulfan
contaminated tobacco.
 Working at endosulfan production centers ,
direct ingestion.
Exposure to
endosulphan
44
Health effect and symptoms
Hypersensitive to stimulation, sensation of
tingling or creeping on skin.
Headache, dizziness, nausea, vomiting,
mental confusion, hyper excitable state.
In severe cases: convulsions, seizures, coma
and respiratory depression.
9000 persons have been reported to have
carcinogenic and mutagenic effects due to
endosulphan usage. ( Shekar et al 2005)
Endosulfan was sprayed in the cashew
plantations in Kasaragod District (Kerala)
since 1976, till 2001 regularly thrice every year.
The intensive use of
Endosulfan resulted
in a chemical
disaster……
46
47
48
49
(http://dathathreya-ayurveda.com)
THE LIVING DEAD…………
Kerala`s
endosulfan
victims…
50
Sainaba-whozz overgrowth of
head caused her death……….
51
A cry for life………
52
53
54
SO…....
55
56Say ‘NO’ to ENDOSULFAN………
Active dust,
Toxic Metal
Silica dust containing dust Causes Silicosis
Asbestos fibre Causes Asbestosis
Cotton dust Causes Byssinosis
Beryllium Berylliosis
Iron dust Causes Siderosis
Arsenic Arsenicosis
Nickel Ulcers, cancer
Chromium Chrome ulcer
Lead Causes anemia
Mercury Affects neuromuscular coordination
CLASSIFICATION OF TOXIC CHEMICALS
BASED ON THE ORGAN / SYSTEMS THEY ARE AFFECTING
Grouping Based on
Effects
Toxic Substances Systems affected
Nerve poison Carbon disulphide Leads to confused state of mind
Carcinogen Benzidine Produces cancer
Stress factor Occupational disease Effect on the body
Arsenic roasting units Arsenic poisoning Lung cancer
IRREVERSIBLE EFFECTS
Asbestos mines, asbestos
handling
Asbestosis, mesothelioma Lung function is adversely
affected –cancer
Benzene handling units Benzene poisoning Toxic anemia, bladder
tumor
Beryllium Beryllium poisoning Cancer
Chromium Chrome poisoning Chrome ulcer-nasal
septum perforation, lung
cancer
Dye intermediate mfg. Cancer Bladder cancer
Ferro-manganese units Manganese poisoning Lower limbs coordination
affected
Noise Permanent shift Deafness
Stark, J. (2009)
Prevention
Minimizing the
release of
pollutants into the
environment
Reducing
personal
exposure to
toxicants or
pollutants in
the
environment
Education and
awareness
creation
It has been estimated that 30-40
percent of all cancers can be prevented
by lifestyle and dietary measures alone.
Try to avoid carcinogens and factors
increasing cancer risk.
Have more cancer protective substances
and be physically active.
Change your lifestyle to be more
protected
(Conney et al, 2004)
 Obesity.
 Nutrient sparse foods such as concentrated
sugars and refined flour products that contribute
to impaired glucose metabolism (which leads to
diabetes).
 Low fiber intake.
 Consumption of excess red meat and saturated
fats
 Regular consumption of alcohol and tobacco.
Factors increasing cancer risk
Cancer protective substances
Vegetables, fruits, whole grains,
herbs, nuts and seeds contain an
abundance of phenolic compounds,
terpenoids, sulfur compounds,
pigments, and other natural
antioxidants that have been
associated with protection from
and/or treatment of conditions such
as cardiovascular disease and cancer.
Conclusion1) Do not smoke; if you smoke, stop doing so. If you fail to stop, do not smoke in
the presence of non-smokers.
2) Avoid Obesity.
3) Undertake some brisk, physical activity every day.
4) Increase your daily intake and variety of vegetables and fruits.
5) If you drink alcohol, whether beer, wine or spirits, moderate your
consumption.
6) Care must be taken to avoid excessive sun exposure. It is specifically
important to protect children and adolescents. For individuals who have a
tendency to burn in the sun, active protective measures must be taken
throughout life.
7) Apply strictly regulations aimed at preventing any exposure to known
cancer-causing substances. Follow all health and safety instructions on
substances which may cause cancer
http://www.cancercode.eu /
"
All substances are
poisons ; there is
none which is not a
poison. The right
dose differentiates
a poison from a
remedy"
(Paracelsus, 1493-1541)
65

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Carcinogenicity in Relation to Environmental Pollution

  • 2. Industrial and agricultural activities, in the last 50 years, have caused the significant increase in the concentration of toxic pollutants in environment :  Polycyclic aromatic hydrocarbons (PAHs),  Polychlorinated biphenyls (PCBs)  Chlorophenols  Nitrophenols  Benzene,ethylbenzene, toluene and xylene( BTEX),  Organic solvents. Most of these substances are mutagenic and carcinogenic. Environmental pollution of air, water and soil with carcinogenic chemicals accounts for >55% of all cancers. (IARC/WHO, 2013). INTRODUCTION
  • 3.  Cancer refers to a number of diseases characterized by uncontrolled growth and spread of abnormal cells.  Carcinogenic effects of chemicals may be delayed for as long as 30 years.  Other carcinogens produce more immediate effects.  Most carcinogens are unreactive or secondary carcinogens but are converted to primary carcinogens in the body.  Numerous factors, such as heredity, affect the susceptibilities of different individuals to cancer- causing agents. (Lancet, 2005)
  • 4. Cont.…  Cancer can affect almost anyone at anytime in their lives.  Cancer can occur in almost any place in the body: Lung, Skin, Breast, Prostate, Colon, and even the Blood (Leukemia)  In December 2012 list by IARC, 328 substances either known to cause or suspected of causing cancer were identified.
  • 5. Carcinogens A carcinogen is a substance or agent known to cause cancer or produces an increase in incidence of cancer in animals or humans. Carcinogens may be chemical substances; physical agents, UV radiation; or biological agents, such as certain viruses and bacteria. A carcinogen may be the initiator — the agent that alters or damages DNA, the basic coding system of cells. It may also be promoter — encouraging out-of- control cell growth. (Gurr. et,al 2001)
  • 6. Cancer is a Global Concern World Health Organization estimates that 80 per cent of cancers are caused by occupational or environmental factors, including exposure to hazardous chemicals and radiations. (WHO, 2012 http://www.who.int/)
  • 7. Cont.. • There were an estimated 14.1 million cancer cases around the world in 2012, of these 7.4 million cases were in men and 6.7 million in women. This number is expected to increase to 24 million by 2035 due to alarming increase in environmental pollution. • Lung cancer was the most common cancer worldwide contributing 13% of the total number of new cases diagnosed in 2012. • Breast cancer (women only) was the second most common cancer with nearly 1.7 million new cases in 2012. • Colorectal cancer was the third most common cancer with nearly 1.4 million new cases in 2012. (IARC, 2013)
  • 8. Entry of Carcinogen into Human Body
  • 9. Ecokinetic properties of a pollutant ENVIRONMENT Pollutant released into environment Transport, Photochemical reaction, Adsorption, Sedimentation Sediment SINK
  • 10. Biokinetic properties of a pollutant ORGANISM BIOACCUMULATION POLLUTANT, DOSE DISTRIBUTION METABOLISATION MetaboliteExcretion of compound Metabolite Compound
  • 11. RISK = Hazard x Exposure
  • 12. Xenobiotics, Carcinogens, Environmental Chemicals. Reactive metabolites, Epoxides, carbonium ions, Quinines, alkyl halides. TOXICITY DNA damage Water-soluble conjugate detoxificationbinding excretion Bile, urinecancer DNA repair Fate of a carcinogen
  • 13. Acquired environmental factors chemicals ,radiation ,viruses Changes in genome of somatic cells Activation of growth promoting oncogenes Inactivation of cancer suppressor genes Expression all altered gene products and loss of regular gene products MALIGNANT NEOPLASM Genetic factors
  • 14. Mutation A change in the DNA molecule Process which produces changes in the DNA that may be inherited. Mutations in certain genes could lead to malignant transformation of the cell. Many mutagens are supposed to be carcinogenic.
  • 15. Metabolic activation of mutagens PROMUTAGEN ACTIVE (ULTIMATE) MUTAGEN DNA ADDUCT (OR OTHER CHEMICAL MODIFICATION OF DNA BASES) MUTATION enzymes metabolic activation TUMOR
  • 16. Carcinogens in Environment • Chemicals (different pollutants)  Alkylating agents  Aromatic hydrocarbons (e.g. benzo(a)pyrene)  SMOKE Main problem is due to cigarette smoking • Physical (ionizing radiation, UV-radiation) • Biological (viruses, transposable elements) (Yoo,Y.D 2012)
  • 17. Cigarette Smoking• Cigarettes are smoked by over 1.1 billion people. While smoking rates have leveled off or declined in developed nations, in developing nations tobacco consumption continues to rise at a rate of around 3.4% per annum. • Worldwide, tobacco use causes more than 5 million deaths per year, and current trends show that tobacco use will cause more than 8 million deaths annually by 2030 due to its carcinogenic nature. • In India, 96 cigarettes are consumed by per adult per year. (Federal Trade Commission Cigarette Report for 2013, Washington)
  • 18. Benzo(a)pyrene (PAHs) • Polycyclic aromatic hydrocarbon. • Carcinogenic activity confirmed. • A product of combustion processes (e.g. tobacco smoking) • A metabolic product binds to DNA → adduct (a compound that results from addition). • Presence of adduct can cause mutation and ultimately to cancer. Metabolic conversion binds to DNA BaP – guanin adduct (Ramaswamy et al. 2002)
  • 19. International Cancer Incidence • Lung cancer is most common cancer worldwide - 1.2 million new cases annually. • Colorectal - 940,000 • Stomach - 870,000 • Liver - 560,000 • Cervical - 470,000 • Esophageal - 410,000 • Head and neck - 390,000 • Bladder - 330,000 • Leukemia - 250,000 • Pancreatic – 216,000 • Kidney – 190,000 • Nervous System – 175,000 • Pharynx – 65,000 (WHO, 2012)
  • 20. International Research Tracking Down Carcinogenic Substances International agencies such as the UN’s International Agency for Research on Cancer (IARC), are continually updating lists of known and suspected carcinogens.
  • 21. Carcinogens: IARC • Group 1: The agent (mixture) is carcinogenic to humans, e.g. Asbestos, inorganic Arsenic etc. • Group 2A: The agent (mixture) probably carcinogenic, e.g. Vinyl chloride, Radon etc. • Group 2B: The agent (mixture) possibly carcinogenic, e.g. Acryl amide, Ethyl di bromide. • Group 3: The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans, e.g. Dichloro benzene. • Group 4: The agent (mixture) probably not carcinogenic, e.g. Trichloroethane, Urethane.
  • 22. Carcinogenic effect of Arsenic  The compounds generally are not mutagenic, but may inhibit enzyme function and induce gene amplification and expression. Inorganic arsenic induces chromosomal aberrations and sister chromatid exchange. (Snow et, al 2002)  In vitro studies indicate that direct oxidative damage of arsenic or its metabolites may play a role in cytotoxicity and pulmonary DNA single-strand breaks. (Yamanaka, 2009)  Chronic inhalation of arsenicals by PVC plant workers has been found associated with lung cancer and angiosarcoma (a rare form of liver cancer) [Falk et al. 2001]  According to IARC and NRC, the association between chronic arsenic exposure and cancer is strongest for skin, lung, bladder, Liver (angiosarcoma) and kidney. [IARC 2004; NRC, 2000].
  • 23. Chromium • Occupational exposure to Cr(VI) compounds in a number of industries has been associated with increased risk of respiratory system cancers. [ATSDR 2000]. • The first epidemiological study of chromate production workers in the United States that demonstrated an association with lung cancer was conducted with 1,445 workers in seven plants engaged in the extraction of chromates from ore from 1930 to 1947. The percentage death due to cancer of the respiratory system was 21.8 [Machle and Gregorius 1948] • Studies of workers in the chromium pigment, chrome-plating, and ferrochromium industries showed a statistically significant association between worker exposure to Cr(VI) and lung cancer [Davies 1984].
  • 24. Cadmium • Cadmium’s toxicity primarily affects the lungs and kidneys, with secondary effects on the skeletal system. • There is sufficient evidence that cadmium metal and a number of cadmium compounds, such as cadmium chloride, oxide, sulfate, and sulfide, are carcinogenic in animals and even to humans. Increased rates of testicular, prostate, and lung cancer in animals have been reported. (Sahmoun et al., 2010) • Occupational studies have suggested possible associations between chronic exposure to cadmium, particularly cadmium oxide, and cancers of the lung, prostate, and genitourinary system such as kidney cancer. The strongest evidence for a linkage between occupational exposure to cadmium and cancer is that of lung cancer. (Sorhan and Esmen 2004)
  • 25. Persistent Organic Pollutants Persistent Organic Pollutants (POPs) are chemical substances that persist in the environment, bioaccumulate through the food web, and pose a risk of causing adverse effects not only on environment but also induce cancer in test animals and human beings. (Sawada,N. 2003)
  • 26. Dioxin  Belong to the “dirty dozen” - a group of dangerous chemicals known as persistent organic pollutants.  In terms of dioxin release into the environment, uncontrolled waste incinerators (solid waste and hospital waste) are often the worst culprits, due to incomplete burning.  Lipophilic in nature, i.e. absorbed by fat tissue.  Their half-life in the body is estimated to be seven to eleven years.  Some 419 types of dioxin-related compounds have been identified but only about 30 of these are considered to have significant carcinogenic effects.  Large amounts of dioxins were released in a serious accident at a chemical factory in Seveso, Italy, in 1976. A cloud of toxic chemicals, including 2,3,7,8- Tetrachlorodibenzo-p-dioxin, or TCDD, was released into the air and eventually contaminated an area of 15 square kilometres where 37 000 people lived and contaminated almost all crops in their fields and about 10% of the population were reported to have carcinogenic effects. (WHO,2011)  Women exposed to TCDD in the Seveso accident in 1976 had abortions because of fears of ill effects. The foetuses had higher levels of chromosome aberrations (Tenchini et al., 1983)  There is evidence that dioxins and furans cross the placenta more readily. (Krowke et al.,1990)
  • 27. Condition Selected exposures Selected occupations Lung Asbestos Chromium Coal tar, pitch Construction trades Welding, plating Steel working Liver Vinyl chloride Plastics mfg. Bladder Benzidine Plastics and chemical manufacturing Blood (leukemia) Benzene Benzene mfg., laboratories Cancer Associated with Occupational Exposure (Stark, J. 2009)
  • 28. Asbestosis • Two types of fibers  Serpentine  Amphibole: Mainly responsible for lung cancer (thin and straight) deeply penetrate into lungs, causes inflammatory reaction lead to formation of fibrous mass which is visible microscopically.
  • 30. UV rays Can cause skin cancers: melanoma, squamous cell carcinoma (epidermis), and basal cell (subcutis) carcinoma It is capable to damage DNA With extensive exposure to sunlight, the repair system is overwhelmed skin cancer They cause mutations in TP53 gene (Benn,J 2005)
  • 31.
  • 32. Melanoma • Melanoma is a cancer that develops in pigment cells called melanocytes. • Melanoma can be more serious than the other forms of skin cancer, because it spreads to other parts of the body at a very fast rate and cause serious illness and death. • The incidence of both non-melanoma and melanoma skin cancers has been increasing over the past decades. Currently, between 2 and 3 million non-melanoma skin cancers and 132,000 melanoma skin cancers occur globally each year. • It is estimated that a 10 per cent decrease in ozone levels will result in an additional 300,000 non-melanoma and 4,500 melanoma skin cancer cases.. (WHO 2013)
  • 33. Melanin Melanin functions as a broad band UV absorbent, Has antioxidant and Radical scavenging properties. Many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. (Brenner et al 2010)
  • 34. Trichloroethylene • The chemical compound trichloroethylene is a chlorinated hydrocarbon commonly used as an industrial solvent in dry clean industry. • A recent analysis by USA EPA (2010) of available epidemiological studies reports trichloroethylene exposure to be associated with several types of cancers in humans, especially kidney, liver, cervix, and lymphatic system. • A meta-analysis of these studies found that occupational exposure to TCE was associated with excess incidences of liver cancer, kidney cancer, and multiple myeloma, with the strongest evidence for the first three cancers (Wartenberg, Reyner et al. 2000)
  • 35. Microbial Carcinogens • Salmonella typhi has been linked to gallbladder cancer . • Sources: sewage overflows, sewage systems that are not working properly, polluted storm water runoff, and agricultural runoff and solid waste dump sites. • Byproducts, or impact of chronic inflammation due to microbial infection, may also be linked to oral cancers. (Meyers et, al 2011)
  • 36. • Chernobyl : An area of 1,00,000 sq km is UNHABITABLE for 20,000 years. FOREVER. Nuclear Radiations! Date: 26 April 1986 Plant Capacity: 900 MW
  • 37. 40 Years Old Uranium Mines in Jaduguda, Jharkhand (1962-2002) Impact of Nuclear Radiation on Humans Cancer in the next 20 to 60 years Deformed babies - FOREVER!
  • 39. After Chernobyl Nuclear Disaster 1986 (New York Academy of Sciences 2003)
  • 40. After American Bombing in Iraq Depleted Uranium (DU) Bombs made out of the Waste from Uranium Enrichment (http://rense.com/general56/dep.htm)
  • 41. Semey: USSR’s Nuclear Testing Site During Cold War (http://www.coldwar.org/articles/40s/soviet_atomic_bomb_test.asp)
  • 42. Postulated Mechanisms of Pesticide Carcinogenicity Mechanism Pesticide Examples Genotoxicity Captan, Endosulfan Tumor promotion Organochlorines Hormonal action Atrazine, ziram Immunotoxicity Aldicarb, 2,4-D Peroxisome proliferation 2,4-D, 2,4,5-T Zahm SH, et al. 2007
  • 43. 43
  • 44.  By breathing air near where it has been sprayed.  Drinking water contaminated directly or through run-offs.  Being in contact with contaminated soil.  Eating contaminated food.  Smoking cigarettes made from endosulfan contaminated tobacco.  Working at endosulfan production centers , direct ingestion. Exposure to endosulphan 44
  • 45. Health effect and symptoms Hypersensitive to stimulation, sensation of tingling or creeping on skin. Headache, dizziness, nausea, vomiting, mental confusion, hyper excitable state. In severe cases: convulsions, seizures, coma and respiratory depression. 9000 persons have been reported to have carcinogenic and mutagenic effects due to endosulphan usage. ( Shekar et al 2005)
  • 46. Endosulfan was sprayed in the cashew plantations in Kasaragod District (Kerala) since 1976, till 2001 regularly thrice every year. The intensive use of Endosulfan resulted in a chemical disaster…… 46
  • 47. 47
  • 48. 48
  • 51. Sainaba-whozz overgrowth of head caused her death………. 51
  • 52. A cry for life……… 52
  • 53. 53
  • 54. 54
  • 56. 56Say ‘NO’ to ENDOSULFAN………
  • 57. Active dust, Toxic Metal Silica dust containing dust Causes Silicosis Asbestos fibre Causes Asbestosis Cotton dust Causes Byssinosis Beryllium Berylliosis Iron dust Causes Siderosis Arsenic Arsenicosis Nickel Ulcers, cancer Chromium Chrome ulcer Lead Causes anemia Mercury Affects neuromuscular coordination CLASSIFICATION OF TOXIC CHEMICALS BASED ON THE ORGAN / SYSTEMS THEY ARE AFFECTING Grouping Based on Effects Toxic Substances Systems affected Nerve poison Carbon disulphide Leads to confused state of mind Carcinogen Benzidine Produces cancer
  • 58. Stress factor Occupational disease Effect on the body Arsenic roasting units Arsenic poisoning Lung cancer IRREVERSIBLE EFFECTS Asbestos mines, asbestos handling Asbestosis, mesothelioma Lung function is adversely affected –cancer Benzene handling units Benzene poisoning Toxic anemia, bladder tumor Beryllium Beryllium poisoning Cancer Chromium Chrome poisoning Chrome ulcer-nasal septum perforation, lung cancer Dye intermediate mfg. Cancer Bladder cancer Ferro-manganese units Manganese poisoning Lower limbs coordination affected Noise Permanent shift Deafness Stark, J. (2009)
  • 59. Prevention Minimizing the release of pollutants into the environment Reducing personal exposure to toxicants or pollutants in the environment Education and awareness creation
  • 60. It has been estimated that 30-40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Try to avoid carcinogens and factors increasing cancer risk. Have more cancer protective substances and be physically active. Change your lifestyle to be more protected (Conney et al, 2004)
  • 61.  Obesity.  Nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes).  Low fiber intake.  Consumption of excess red meat and saturated fats  Regular consumption of alcohol and tobacco. Factors increasing cancer risk
  • 62. Cancer protective substances Vegetables, fruits, whole grains, herbs, nuts and seeds contain an abundance of phenolic compounds, terpenoids, sulfur compounds, pigments, and other natural antioxidants that have been associated with protection from and/or treatment of conditions such as cardiovascular disease and cancer.
  • 63. Conclusion1) Do not smoke; if you smoke, stop doing so. If you fail to stop, do not smoke in the presence of non-smokers. 2) Avoid Obesity. 3) Undertake some brisk, physical activity every day. 4) Increase your daily intake and variety of vegetables and fruits. 5) If you drink alcohol, whether beer, wine or spirits, moderate your consumption. 6) Care must be taken to avoid excessive sun exposure. It is specifically important to protect children and adolescents. For individuals who have a tendency to burn in the sun, active protective measures must be taken throughout life. 7) Apply strictly regulations aimed at preventing any exposure to known cancer-causing substances. Follow all health and safety instructions on substances which may cause cancer http://www.cancercode.eu /
  • 64. " All substances are poisons ; there is none which is not a poison. The right dose differentiates a poison from a remedy" (Paracelsus, 1493-1541)
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