DESCRIBED ABOUT TOXICITY IN HUMAN DUE TO HEAVY METAL BRIEFLY

1. Heavy metal and human
health

2. 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)

3. Factors affecting
toxicity
1. 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. 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.

5. LEAD

6. 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

7. 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 on
the toys.
 stagnant water in
pipes.

8. Absorption
1. GI tract
 Children are at greater risk for lead
absorption(adults:11%-16%,children
: 40% - 50%)
 Absorption increased with fe, ca, zn
deficiency
2. Lungs
 50% - 70% if < 1 μm
3. Skin
 Inorganic lead is non-absorbable
 Organic lead is readily absorbed

9. Distribution
Exchanged 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

10.  Crosses the placenta
 Exists in breast milk.
 Malnutrition and iron
deficiency-higher lead
absorption in the mother.

11. 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

12.  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

13. Symptoms
 Acute toxicity-
 vomiting, constipation, ataxia,
somnolence
 Lead nephropathy
 Elevated intracranial pressure
(icp)-lead encephalopathy.

14.  Chronic toxicity (plumbism)
 Low-level exposure over a long
time
• Early symptoms-
- Muscle weakness, and
paresthesias
- Confusion/ irritability
- Metallic taste in mouth

15.  Late complication-
Diminished libido
Anemia
Peripheral neuropathy in
extensor surfaces k/a wrist
drop and/or foot drop (most
common in adults)

16. Burton
line
Wrist drop

17. • In children-
• Permanent learning disability
and behavior disorders.
• Hearing loss, aggression
• Delayed growth.

18. 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

19.  Free erythrocyte
protoporphyrin level (FEP)
 High blood lead lead but FEP
normal- acute
 Both are high- chronic

20. Regulatory limits
EPA –
 15 ppb in drinking water,
OSHA-
 0.15 µg/cu.m in air for 8 hrs work

21. MERCURY

22. 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

23.  Paint, fungicide .
 Thermometers, thermostats,
fluorescent light bulbs, amalgams
 Antiseptics (mercurochrome and
merthiolate),
 Vaccines (flu vaccines contain
thiomersal)

24. 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

25. 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)

26.  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

28.  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

29. Elemental
MercuryAcute-
 Acute necrotizing bronchitis(vapor
inhalation)
 Pneumonitis
 Skin, and nose irritation

30.  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)

31. Mercurial erethism

32. 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

33. Acrodynia /Pink disease

34. Organic Mercury
 Methylmercury, dimethylmercury and
ethylmercury
 effects the CNS ( Minamata disease)
 Teratogen with large chronic exposure
◦ Asymptomatic mother
◦ congenital Manimata disease in
infants

35. Diagnosis
 Elemental and inorganic mercury-
urine collection
 organic mercury- whole-blood (s’d
be < 6 μg/L)
 Hair analysis is more reliable

36. 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

37. Arsenic toxicity

38. 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

39. 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))

40. 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

41. Pharmacokinetics
A. 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

42. Mechanism of
actionAs+3 :
◦ inhibit SH- containing enzymes
(glutathione reductase and thioredoxin
reductase)
◦ Inhibit the Krebs cycle (inhibit pyruvate
dehydrogenase) and oxidative
phosporylation.

43. 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

44. Arsenic trioxide-
 Prolongation of cardiac action
potential duration
 Induce atherosclerosis
 Platelet aggregation
 Reducing fibrinolysis

45. 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.

46. 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.

47.  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.

48. Mees line
Palmar keratosis

49. Reproductive system:
 spontaneous abortion
 lower birth weights
Carcinogenic: cancers of the
skin, liver, respiratory tract,
kidney, bladder and
gastrointestinal tract

50. Diagnosis
1. Urine analysis
2. whole blood arsenic
measurements
3. hair and fingernails
 Acute hemolytic anemia in arsine
exposure

51. Regulatory limits
 EPA - 0.01 ppm in drinking water.
 OSHA - 10 µg per cubic meter for
8 hrs workplace air

52. Cadmium

53. Sources
 Soils and rocks
 Coal and mineral fertilizers
 Batteries,
 Pigments
 Metal coatings
 Plastics
 Electroplating.
 Tobacco smoking largest source

54.  Accumulates in leaves, fruits and
seeds.
 Accumulates in animal milk and
fatty tissues
 Seafood, such as molluscs and
crustaceans

55. 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.

56. 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

57. Itai itai disease

58.  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

59. Barium
Source-
 Electrodes
 Vacuum tubes
 Oxygen-removing agent
 Barium sulfide- fluorescent lamps
 Barium sulfate-diagnostic medicine
 Drilling muds, paint, bricks, ceramics,
glass, and rubber.

60.  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)

61.  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

62. Chromium
Source
 Persistent in sediments in water
 Stainless steel
 Electroplating, magnetic tapes
 Pigments for paints, cement, paper,
rubber, composition .
 Wood preservatives.

63.  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

64. 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

65. 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

66.  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

67. Discoloration of skin Baldness
SELENOSI
S

68. Regulatory limits
 EPA – 50 ppb drinking water.
 OSHA – 0.2 mg per cubic meter
of workroom air for an 8-hour
work shift.

69. Silver
 Jewelry, silverware,
 Dental filling
 Brazing alloys and solders
 Mirrors
 Photographic film
 Disinfectants and antibacterial
agent.

70. 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

71. Argyria

72.  EPA – drinking water not to
exceed 0.10ppb
 OSHA – in workplace air 0.01
mg/m³ for an 8-hour workday

73. 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

74. 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.

75. Kayser-fleischer ring(deposition of cupper in
descemet membrane of eye