heavy metal and human health
TRANSCRIPT
Heavy metal and human health
Background Those metals with a specific gravity
of greater than 4.0.
Mainly produced from industrial
activities
most hazardous heavy metals are-
1. arsenic (As)
2. lead (Pb)
3. mercury (Hg)
4. cadmium (Cd)
Factors affecting
toxicity1. The total dose absorbed
2. The exposure either acute or
chronic.
3. Age of the person
E.G.-Young children are more
susceptible to lead
4- The route of exposure
E.g.- Elemental mercury is
inert in the gastrointestinal
tract and through intact skin,
but inhaled or injected
elemental mercury have
disastrous effects.
LEAD
Mode of Exposure 2nd most hazardous substance
Lead poisoning is the most
important chronic environmental
illness
In the environment lead is in
organic and inorganic
compounds.
Inorganic lead compounds are
less toxic
Occupational exposure
Battery makers
Cable makers
Glass makers/polishers
Gunshot/gun barrel makers
Jewelers
Lead burners
Painters
Pigment makers
Pipe cutters
Printers
Non-occupational exposure
Battery burning
Bullet retention
Cooking in leaden pots
Ingestion of paints
gasoline
cigarette smoke.
surface paints onthe toys.
stagnant water inpipes.
Absorption1. GI tract
Children are at greater risk for lead absorption(adults:11%-16%,children : 40% - 50%)
Absorption increased with fe, ca, zndeficiency
2. Lungs
50% - 70% if < 1 μm
3. Skin
Inorganic lead is non-absorbable
Organic lead is readily absorbed
DistributionExchanged in 3 compartments:
1. Blood
2. Soft tissue (liver, kidneys, lungs,
brain, spleen, muscles, and heart)
3. Mineralizing tissues (bones and
teeth). In bone it is stored for
several years. Redistribution
occurs in pregnancy
Crosses the placenta
Exists in breast milk.
Malnutrition and iron
deficiency-higher lead
absorption in the mother.
Pathophysiology Lead inhibit enzyme with sulfhydryl
groups Delta amino levulinic acid dehydratase
(formation of porphyrin ring) and ferrochelatase (incorporation of iron into porphyrin ring) inhibited, decrease in heme production
Basophilic stippling of erythrocytes
Pb2+ disturbs intracellular ca2+
homeostasis(calmodulin, protein
kinase C, ca2+ -dependent K+
channels and neurotransmitter
release disturbed)
The burton line or gingival lead line
in gums
CNS- Children are most succeptible
Symptoms Acute toxicity-
vomiting, constipation, ataxia,
somnolence
Lead nephropathy
Elevated intracranial pressure
(icp)-lead encephalopathy.
Chronic toxicity (plumbism)
Low-level exposure over a long
time
• Early symptoms-
- Muscle weakness, and
paresthesias
- Confusion/ irritability
- Metallic taste in mouth
Late complication-
Diminished libido
Anemia
Peripheral neuropathy inextensor surfaces k/a wristdrop and/or foot drop (mostcommon in adults)
Burton
line
Wrist drop
• In children-• Permanent learning disability
and behavior disorders.
• Hearing loss, aggression
• Delayed growth.
DIAGNOSIS Blood lead level (BLL)(> 9 μg/dl )
CBC- basophilic stippling of red
rbcs,anemia(microcytic,hypochoch
romic)
Lead in bones (x-ray fluorescence,
XRF)
Acute poisoning- radiographic
examination of the abdomen
Free erythrocyte
protoporphyrin level (FEP)
High blood lead lead but FEP
normal- acute
Both are high- chronic
Regulatory limits
EPA –
15 ppb in drinking water,
OSHA- 0.15 µg/cu.m in air for 8 hrs work
MERCURY
Sources 3rd on the top hazardous
substances.
Naturally-degassing of the earth's
crust and volcanic eruption.
Mining, smelting, and industrial
discharges
Atmospheric mercury comes to the
earth in rain
Paint, fungicide .
Thermometers, thermostats,
fluorescent light bulbs, amalgams
Antiseptics (mercurochrome and
merthiolate),
Vaccines (flu vaccines contain
thiomersal)
Mode of Exposure three forms Elemental◦ Inhalation(main source)
◦ Poorly through GI tract, Skin contact
Inorganic◦ Poorly through GI tract(7-15%).
◦ Dermal exposure causes toxicity
Organic◦ Lipid soluble
◦ well absorbed via GI (90-100%); lungs and skin
◦ Cross BBB and affects CNS
◦ Can cross placenta and into breast milk
Pathophysiology Binds to sulfhydryl of enzymes
(cellular stress response, protein
repair, and oxidative damage
prevention.)
Methylmercury inactivates Na+/K+-
ATPase(membrane depolarization
eventual cell death)
Industrial mercury-inorganic form
aquatic organisms and vegetation
convert it to methylmercury.
Then mercury becomes
biomagnified in the fish. (Fish
protein binds about 90% of the
consumed methyl mercury )
Even by cooking it cannot be
removed
Minamata disease-(Minamata Bay)
After eating methyl mercury containing fish neurologic damage such as visual loss, extremity numbness, hearing loss, and ataxia
Babies exposed in utero and also exposed after birth through breast milk
Infants with mental retardation, blindness, deafness, and seizures
Elemental
MercuryAcute-
Acute necrotizing bronchitis(vapor
inhalation)
Pneumonitis
Skin, and nose irritation
Long term exposure affects CNS.
◦Early: insomnia, impaired memory, mild tremor
◦Late: erethism (red palms, emotional lability (irritability and nervousness), ◦ renal toxicity (proteinuria, or nephrotic syndrome)
Mercurial erethism
Inorganic Mercury Gastrointestinal ulceration and hemorrhage
Proximal tubular necrosis and anurea
Acrodynia (pink disease, erythroedema, or
feer’s disease) in dermal exposure
◦ Maculopapular rash(fingertips, toes )
◦ Pus-filled skin eruptions
◦ Swollen and painful extremities
Acrodynia /Pink disease
Organic Mercury Methylmercury, dimethylmercury and
ethylmercury
effects the CNS ( Minamata disease)
Teratogen with large chronic exposure
◦ Asymptomatic mother
◦ congenital Manimata disease in infants
Diagnosis Elemental and inorganic mercury-
urine collection
organic mercury- whole-blood (s’d
be < 6 μg/L)
Hair analysis is more reliable
Regulatory limits EPA – 2 ppb in drinking water
FDA – 1 part of methylmercury in
a million parts of seafood.
OSHA – 0.1 mg of organic
mercury per cubic meter of
workplace air for 8 hrs
Arsenic toxicity
Source Most common cause of acute heavy
metal poisoning in adults
Number 1 on the top hazardous
substances.
Smelting process
Galvanization
Manufacturing of pesticides that contain arsenic. (Arsine gas )
Paints, pesticides
Tobacco smoke
Organic arsenic- seafood
Mode of Exposure Three forms, organic and
inorganic arsenic compounds,
arsine gas.
Inorganic arsenic is more harmfull
Inorganic arsenic- reduced (trivalent
as (iii)) and oxidized (pentavalent
as(v))
Toxicocokinetics Inorganic arsenic are readily
absorbed through the GI tract
Then accumulate in tissues and
body fluids.
Also readily deposited in the hair
and nails
PharmacokineticsA. Pentoxide
Trioxide increases its toxicity and bioavailability
B. Trioxide
( Monomethylarsonous acid (mma(iii), dimethylarsinous acid (dma(iii))
Methylation decreases toxicity and increases excretion
trioxideGSH
MMA(III)+
DMA(III)
Arsenate methyl
transferase
liver
Mechanism of
actionAs+3 :
◦ inhibit SH- containing enzymes (glutathione reductase and thioredoxinreductase)
◦ Inhibit the Krebs cycle (inhibit pyruvatedehydrogenase) and oxidative phosporylation.
As+5
◦Replace the phosphate ester bond in ATP (arsenic ester stable bond )
• High carcinogenic(inhibition of DNA repair due to interaction of arsenic with –SH group)
Irritant effect
Endothelial damage, loss of capillary integrity
Arsenic trioxide-
Prolongation of cardiac action
potential duration
Induce atherosclerosis
Platelet aggregation
Reducing fibrinolysis
Symptoms of
toxicityAcute toxicity:
Hematemesis, abdominal pain
rice-water diarrhoea
Garlic-like breath
Thirst and metalic taste
Contact dermatitis
Arsine gas exposure- acute hemolytic
anemia and striking chills.
Chronic toxicity: Multiple organ dysfunctions problems
Neuronal :peripheral neuropathy, encephalopathy, dementia, cognitive impairment, hearing loss
CVS: hypertension, myocardial infarction, anemia and leukopenia
Respiratory: pharyngitits, laryngitis
GIT: severe abrominal cramping and hematemesis.
kidney and liver damage
Skin abnormalities:
darkening of the skin
appearance of small "corns" or
"wart" on the palms, soles ( palmar
keratosis).
whitish lines (Mees lines) found on
the fingernails.
Mees line
Palmar keratosis
Reproductive system:
spontaneous abortion
lower birth weights
Carcinogenic: cancers of the
skin, liver, respiratory tract,
kidney, bladder and
gastrointestinal tract
Diagnosis1. Urine analysis
2. whole blood arsenic
measurements
3. hair and fingernails
Acute hemolytic anemia in arsine
exposure
Regulatory limits EPA - 0.01 ppm in drinking water.
OSHA - 10 µg per cubic meter for
8 hrs workplace air
Cadmium
Sources Soils and rocks
Coal and mineral fertilizers
Batteries,
Pigments
Metal coatings
Plastics
Electroplating.
Tobacco smoking largest source
Accumulates in leaves, fruits and
seeds.
Accumulates in animal milk and
fatty tissues
Seafood, such as molluscs and
crustaceans
Toxicity Acute-
Vomiting and diarrhoea.
Severe respiratory irritation
Chronic-
Kidneys damage mostly PCT(increased excretion of α 2, β 2, gamma globulins)
Lung damage(occupational exposure)
Fragile bones(loss of ca in urine)
Testicular degeneration
prostate cancer.
itai-itai disease syndrome-1. severe renal dysfunction
2. damage to bone structure.
3. elderly multiparous women mostly
affected
4. poor nutritional status
5. Chronic exposure
Itai itai disease
Regulatory limits
EPA – 5 ppb cadmium in drinking
water
FDA – concentration in bottled
drinking water should not exceed
0.005 ppm
OSHA – an average of 5 µg/cu.m. of
workplace air for an 8-hour workday
BariumSource-
Electrodes
Vacuum tubes
Oxygen-removing agent
Barium sulfide- fluorescent lamps
Barium sulfate-diagnostic medicine
Drilling muds, paint, bricks, ceramics,
glass, and rubber.
Health effects
● Short term exposure- vomiting,
diarrhoea, increased or decreased
blood pressure, muscle weakness.
● Large amounts - high blood pressure,
heart muscle paralysis, kidney damage,
respiratory failure
barium carbonate or chloride-
hypokalemia(adverse effect on heart)
Regulatory limits
EPA - 2.0 ppm in drinking water.
OSHA - 0.5 mg of soluble barium
compounds per cubic meter of
workplace air for 8 hour shifts
ChromiumSource Persistent in sediments in water
Stainless steel
Electroplating, magnetic tapes
Pigments for paints, cement, paper,
rubber, composition .
Wood preservatives.
Health effects
Chromium (VI) is human carcinogens
● Breathing- irritation to nose; nose ulcers; runny nose ,asthma
● Skin contact- skin ulcers, Allergic reactions
● Long term exposure- damage to liver, kidney ,circulatory and nerve tissues
chromium(III) in high conc. can lead to DNA damage
Haemolysis
Regulatory limits
EPA– 0.1 ppm (parts per million)
in drinking water.
FDA – should not exceed1 ppm in
bottled water.
OSHA – 0.0005 and1.0 milligram
per cubic meter of workplace air
for an 8-hour
Selenium Rocks and soils
Electronics industry
Glass industry , plastics, paints,
enamels, inks, and rubber
Pharmaceuticals, nutritional feed
additive for poultry and livestock
Pesticide formulations
Antidandruff shampoos
Fungicides
Health effects
Upper Intake Level is 400 µg/day.
● Short-term oral exposure -nausea,
vomiting, and diarrhea.
● Chronic oral exposure-produce
selenosis.(hair loss, nail brittleness,
neurological abnormalities.,discolouration
of skin)
● Brief aerosol exposures -irritation,
bronchitis, difficulty breathing
Longer-term exposure-respiratory
irritation, bronchial spasms
Discoloration of skin Baldness
SELENOSI
S
Regulatory limits
EPA – 50 ppb drinking water.
OSHA – 0.2 mg per cubic meter
of workroom air for an 8-hour
work shift.
Silver Jewelry, silverware,
Dental filling
Brazing alloys and solders
Mirrors
Photographic film
Disinfectants and antibacterial
agent.
Health effects Exposure to high levels for a long
period-argyria(blue-gray
discoloration of the skin and other
body tissues)
Aerosol exposure-breathing
problems, lung and throat irritation,
and stomach pains.
● Skin contact with-mild allergic
reactions
Argyria
EPA – drinking water not to
exceed 0.10ppb
OSHA – in workplace air 0.01
mg/m³ for an 8-hour workday
Tin Dinnerware and canned food
Food standards agency in UK set upper limits of 200 mg/kg.
Un-lacquered tin cans with food of a low ph(fruits and pickled vegetables) contain higher conc.
Interference with the iron and copper metabolism(heme and cytochrome P450)
Nausea, vomiting and diarrhea
Copper Called copperiedus
Eating acid foods cooked in uncoated copper cookware
Excess copper in drinking water
Free copper in blood generates ROS these damage proteins, lipids and DNA
Acute- vomiting, hematemesis, hypotension, melena, coma, jaundice, and haemolytic anaemia
Chronic- damage the liver and kidneys.
Kayser-fleischer ring(deposition of cupper in
descemet membrane of eye