Real Hazards around us..

1. Toxic Minerals
Muhammad Mansoor Javed
Institute of Animal Sciences

2. Introduction
Minerals
Functions
• Structural
• Physiological
• Catalytic
• Regulatory

3. Macro minerals
• Calcium, Phosphorus, Potassium, Sulfur, Sodium, Chloride
Trace minerals
• Iron, Zinc, Copper, Molybdenum, Selenium, Iodine, Manganese,
Cobalt

4. Toxic Minerals or “heavy metals”
• Found naturally in the earth crust
• Toxic and poisons in nature even at low concentration
• Exposed in ecosystem due high industrial uses, extensive mining,
smelting of ores, burning of coal, gas and oil, incineration of waste
materials around the world
• Environment, Plants, Animals and Humans are exposed to highest
levels

5. • Toxic metals are now everywhere and affect everyone on planet
earth. They have become a major cause of illness, aging and even
genetic defects
• Most common toxic minerals are Arsenic (As), lead (Pb), Mercury (Hg)
and Cadmium (Cd)

6.  Lead (Pb)
• Soft gray metal, Naturally occur
in earth
• Occurs in organic and inorganic
form
• Insignificant environmentally
until about 1800
• Human activities mobilized lead
in the Environment

7. • Maximum concertation of lead allowed according to United State
Environmental Protection Agency (USEPA, 1987)
In Sludge (Soil) 85 mg/kg
In drinking water 0.01 mg/l
In aquatic H20 supporting marine life 0.0058 mg/l
Air 50 µg/m3

8. Sources of exposure
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
• Target shooting
• lead containing herbal medicines
• Ingestion of paints
• still used as additives in gasoline in
several countries
• Exists in cigarette smoke
• surface paints on the toys
• stagnant water in pipes
• Cosmetics

10.  Absorption
1. Gastro intestinal tract (GIT)
• Higher absorption in children than adults
• Lead absorption is dependent on several factors, including the
physical form of lead, the particle size ingested, the GI transit time,
and the nutritional status of the person ingesting.
• Increased with Fe, Ca, Zn deficiency
• Decreased if phosphorus, riboflavin, vitamin C, and vitamin E are in
the diet
• Adults: 11% - 16%
• Children : 40% - 50%

11. 2. Lungs
• 50-70 % of lead inhaled can be absorbed through lungs
3. Skin
Inorganic lead is unabsorbed
Organic form readily absorbed

12.  Distribution in the body
• Absorbed lead is exchanged primarily among the following 3
compartments:
Blood (Max. limit: children < 5 µg/dl, Adults 10 µg/dl)
(ATSDR, 2012)
Soft tissue (liver, kidneys, lungs, brain, spleen, muscles, and heart)
Mineralizing tissues (bones and teeth)
• Lead readily crosses the placenta and exists in breast milk, with the fetus
retaining lead cumulatively throughout gestation.
• Specific health problems, such as malnutrition and iron deficiency, may
result in higher lead absorption in the mother. Elevated maternal lead
levels subsequently result in higher lead distribution to the fetus

13.  Elimination from body
1. Kidney is responsible for 65% of lead’s elimination
• Process is dependent on glomerular filtration rate and renal plasma
flow
2. Biliary excretion is responsible for 35% of lead’s elimination

14.  Toxicity
• Classified as carcinogenic by Agency for research on cancer
• Lead interferes with a variety of body processes and is toxic to many organs
and tissues. The heart, bones, teeth, intestines, kidneys, thyroid gland
reproductive and nervous systems represent its main targets
• High affinity for SH groups toxic to multiple enzymes systems
• Affect Ca requiring cell function by binding to CaBP
• Anemia due to inhibition of chain reaction for haem synthesis
• Toxic effect on renal tubules
• Inhibit 5-pyrimidine nucleotides (Active precursor of DNA and RNA)
• Affect motors nerves ultimately CNS (Affect CPK II system)

15. • Affects virtually every system in the body
Central nervous system
Blood (Inhibition of heam synthesis)
Endocrine
Cardiovascular
Renal
Gastrointestinal
Musculoskeletal
Immune and reproductive system

16.  Symptoms of lead toxicity

17.  Treatment of lead Toxicity
• Dimercaprol (also referred to as British antilewisite [BAL])
• Chelating agent Removes intra cellular and extracellular lead
• Recommended as an agent of first choice for patients with lead
toxicity.
• With high BLLs (i.e, > 70 µg/dl), it is used in conjunction with EDTA
• Allows extracellular lead to be eliminated through renal system

18.  Arsenic (As)
• 20th most Abundant mineral in earth crust
(1.5-3.0 mg /kg)
• Arsenic exists in the environment in major
three forms,
Organic (arsine)
Inorganic arsenic compounds (arsenite)
Elemental form

19. • “King of poisons, poison of kings”
• Odorless and taste less properties inorganic
compounds makes it ideal poison i.e.
arsenic tri-oxide (white arsenic)
• Tiberius Britannicus in 55 CE poisoned by his
step brother Nero, who later secured
position of emperor of Rome

20. Exposure to arsenic
• Inorganic arsenic poisoning can be related to human activities such as
mining and smelting
• Dissolved naturally in ground water and soil
• Marine food like fish (less toxic organic form)
• Herbicides, fungicides contain arsenic
• In cosmetics 19th to early 20th century for whitening and rosy cheeks
• Common source of accidental poisoning

22. Absorption
• Many arsenic compounds (especially inorganic arsenic) are readily
absorbed through the GI tract when delivered orally in humans
• Absorption within the lungs is dependent upon the size of the arsenic
compound, and it is believed that much of the inhaled arsenic is later
absorbed through the stomach after (respiratory) mucociliary
clearance
• After the absorption of arsenic compounds, it accumulate in tissues
and body fluids
liver, kidneys, lung, spleen, aorta, and skin
Arsenic compounds are also deposited in the hair and nails

23.  Tolerable levels of arsenic in Diets
Diet Level
Human beings Tolerable Daily Intake (PTDI) for inorganic arsenic is
0.002 mg/kg bodyweight
Goats 30 mg/kg BW
Horses 6.5 mg/kg BW
Sheep 11 mg/kg BW
Fish 10 mg/Kg BW

24.  Toxicity
• In blood bind to the globulin portion of hemoglobin
• Impair cellular respiration by inhibiting mitochondrial enzymes and
oxidative phosphorylation
• Block pyruvate dehydrogenase in Kreb's cycle
• Binds to SH- containing proteins thus reacts with a variety of
structural and enzymatic proteins leading to inhibition of their activity
(like glutathione reductase and thioredoxin reductase)
• Trivalent arsenic inhibits cellular glucose uptake, gluconeogenesis,
fatty acid oxidation

25. • It can replace phosphate in many reactions can replace the stable
phosphate ester bond in ATP and produce an arsenic ester stable
bond which is not a high energy bond
• Arsenic has very high carcinogenic potential. The mechanisms
responsible for this may be inhibition of DNA repair and alterations in
the status of DNA. Due to inactivation of DNA-binding proteins,
transcription factors and DNA-repair proteins by interaction of arsenic
with –SH group.
• Arsenic has irritant effect and has the ability to induce endothelial
damage, loss of capillary integrity, and capillary leakage

28.  Treatment
• Normal values
Spot urine ~ 11 µg/L
Whole blood < 7 µg/dl
• BAL (British Anti lewisite) or Dimercaprol @ 3-5 mg/Kg I/M every 4 to
6 hrs
 lewisite is arsenic containing vesicant gas
• DMSA (Succimer)

29.  Mercury (Hg)
• Mercury is rarely occurring free element in
earth's crust
• Silvery, heavy, mobile, liquid phase
• Only liquid metal at room temp.
• Occurs in three forms (elemental, inorganic
salts, and organic mercurial compounds)
• Contamination results from mining,
smelting, and industrial discharges
• Almandine mine in Spain having Cinnabar
ore (HGs) is in operation from 400 BC

30.  Sources of exposure
• Elemental: Barometers, batteries,
electroplating, fingerprinting products,
Fluorescent and mercury lamps, thermometers,
silver and gold production
• Organic: Insecticidal, fungicidal, bactericidal
products, aquatic products like fish (have
deposited mercury from industrial waste
deposited in water)
• Inorganic: Cosmetics, mirror silvering,
photography, tattooing inks, wood preservation

32.  Absorption
• Elemental
Liquid at room temperature that volatizes readily
Inhalation is the main source of toxication, rapid distribution in body
by vapor, poor in GI tract. Can affect CNS. Skin contact may also
considered.
• Inorganic
Poorly absorbed in GI tract, but can be caustic
Dermal exposure has resulted in toxicity

33. • Organic
Lipid soluble and well absorbed via GI, lungs and skin. Cross BBB and
affects CNS
Can cross placenta and into breast milk
The organic form is readily absorbed in the GIT (90-100%); lesser but
still significant amounts of inorganic mercury are absorbed in the
GIT(7-15%). Target organs are mostly the nervous system and kidneys

34.  Toxicity
• Mercury reacts with sulphahydryl groups (SH), resulting n enzymes
inhibition and pathologic alteration of cellular membranes
• Methyl mercury affects CNS
• Target specific sites in brain especially cerebral cortex (visual cortex),
motor and sensory centers, auditory center and cerebellum
Typical neurological symptoms i.e. mental distortion, ataxia, hearing
loss, confusion, movement disorder, anorexia, memory loss,
uncontrolled perspiration
• Mercury vapors affects pulmonary tract
• Corrosive to the skin, eyes and GIT

36.  Out breaks of mercury toxicity
• Japan - 1952, chemical co.
dumped Hg into Minamata
harbor; residents of local fishing
villages contaminated; 100s
affected and 68 died
• Iraq – 1971, poison grain
disaster
Utilization of mercury treated
grains never indented to eat
Imported from Mexico and US

37.  Treatment
• Allowable blood level is 5 ng/mL (nanograms per milliliter)
• urine - 20 ng/mL
• Gastric lavage if the compound is observed on abdominal radiograph series
• Activated charcoal is indicated for GI decontamination because it binds
inorganic and organic mercury compounds
• Whole bowel irrigation until rectal effluent is clear and void of any
radiopaque material

38. • Hemodialysis is used in severe cases of toxicity when renal function has declined.
However, hemodialysis with L-cysteine compound as a chelator has been
successful
• Chelating therapy for acute inorganic mercury poisoning can be done with
Dimercaptosuccinic acid (DMSA), DPCN, or BAL.
• Only DMSA is approved for treating mercury poisoning in children, organic
mercury poisoning, and poisoning due to mercury vapor
• Exchange transfusion has been used as a treatment of last resort

39.  Cadmium (Cd)
• Occurs naturally in the environment in its
inorganic form as a result of volcanic emissions
and weathering of rocks
• Anthropogenic sources have increased the
background levels of cadmium in soil, water and
living organisms
• Maximum allowable contamination levels
Air 0.1-0.2 mg/cubic m
Soil 85 mg/kg
Drinking water 0.005 mg/l
Water supporting aquatic life 0.008

40.  Exposure
• Small particles exist in air as result of smelting, soldering and other
industrial processes
• By-product of zinc, copper, lead ores
• Metal plating, color pigments, batteries, plastic

41. • McDonald’s Shrek glasses were
contaminated with cadmium
• Tobacco smoke important source
of cadmium
• Low levels found in grains,
cereals, leafy vegetables

42.  Absorption
• Inhalation:
18-50 % inhaled absorbed through lungs
Cigarette smoke, smelters etc.
• GIT:
Liver and kidney of meat animals are rich source
6% is absorbed

43. • Absorbed Cd bound to albumin in plasma and red blood cells
• Transported to liver, pancreas, prostate and kidney, with eventual
transfer to kidney
• 50-75% of total body Cd is found in liver and kidney
• Metallothionein: protein rich in cysteine
 Traps Cd especially in kidney
 Synthesis induced by Cd
• Half-life in humans is 22 - 30 years

44.  Toxicity
• Bind to –SH groups
• Competing with Zn and Se for inclusion into metalloenzymes
• Competing with calcium for binding sites
• Kidney toxicity:
Free Cd binds to kidney glomerulus
Proximal tubule dysfunction
• Lung toxicity:
Edema and emphysema by killing lung macrophages (dust cells)

45. • Skeletal effects:
Osteoporosis and osteomalacia (pseudofractures)
• Cancer:
Carcinogenic in animal studies
~8% of lung cancers may be attributable to Cd

47.  Outbreak of Cd toxicity in history
• Itai-itai disease ("it hurts-it hurts disease") was the name given to the
mass cadmium poisoning of Toyama Prefecture, Japan, starting
around 1912
• Increased demand for raw material during Russo-japanese war and
world war 1 increased mining output
• Mining industry waste polluted the river
• Rice fields irrigated with the water of that river results in the
accumulation of toxic minerals in the crop

48. • Induced toxicity in many people
living in that region
• Victims felt severe pain in spine
and joints
• Softening of bones
• Kidney failure

49.  Treatment
• The allowable blood level of cadmium is 0.315 µg/L
• Elements like calcium and selenium are shown to have protective
effect against cadmium-induced toxicity
• Adequate levels of zinc in the body helps to displace cadmium from
the tissues
• Potent antioxidants like Vitamin C, E, glutathione, methionine,
glycine, cysteine has great protective efficiency
• chelation therapy is ineffective so only treatment is to remove source

50. •Thanks for you
attention
•Any questions