A Small Dose of ™ Metal
An Introduction To The
Health Effects of Metals
ENVIRONMENTAL AND
OCCUPATIONAL TOXICOLOGY III
(ENVH 516)
A Small Dose of Metals – 04/13/11
Introduction
Complex relationship to metals
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Nutritionally Important
Toxicologically Important
Medical Important
Chelation
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Ancient Awareness
 Lead - usage began 4000 years ago
 Hippocreates – 370 BC noted abdominal
colic in miner
 Arsenic – therapeutic and a poison (400 BC)
 “Lead makes the mind give way”. The Greek
Dioscerides 2nd century BC
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Historical Awareness
 80 of 105 elements in the periodic table are
labeled as metals
 “Mad Hatter” – mercury exposure
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Thoughts on Metals
 Redistribution
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Naturally occurring – break down of rock
Human – mining, purify, recombine, use
E.g. lead – rise in Greenland ice
 Changed form
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E.g. inorganic to organic mercury
 Occupational exposure
 Home exposure
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Susceptibility to Metals
 Age – young or old?
 Nutrition (competion with essential
metals)
 Allergic response (immune system)
 Form of metal (organic or inorganic)
 Lifestyle – smoking or alcohol
 Occupation
 Home environment (lead paint?)
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Nutritionally Important
Some metals have very important
physiological functions
Cr  Chromium (Cr)
Cu  Copper (Cu)
Fe  Iron (Fe)
Mg  Magnesium (Mg)
Mn  Manganese (Mn)
Se  Selenium (Se)
Zn  Zinc (Zn)
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Chromium (Cr)
• Use – essential element, associated with
insulin, stainless steel, tanning leather
• Source –food supply, inhalation
• Recommended daily – 50-200 µg
• Absorption – intestine
• Toxicity – acute exposure cause kidney
damage, lung cancer
• Facts – comes in different oxidized forms
– Cr3+, Cr6+
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Copper (Cu)
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Use – essential element, widely used
Source – readily available in food
Recommended daily – 1.5-3.0 mg
Absorption – intestine
Toxicity – deficiency – anemia
- excess rare, Wilson’s disease
• Facts – excess treated with penicillamine
- can be toxic grazing animals
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Iron (Fe)
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Use – oxygen carrying hemoglobin
Source – food
Recommended daily – 10-15 mg
Absorption – intestine
Toxicity – excess causes bloody fesses,
bloody vomit, liver damage
• Facts - 3-5 grams in the body
• 67% associated with hemoglobin
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Magnesium (Mg)
• Use – essential nutrient, associated
with many enzymes, antacids
• Recommended daily – 280-350 mg
• Source – food supply, nuts, cereals,
seafood, meats, drinking water
• Absorption – small intestine
• Toxicity – deficiency – convulsions
- excess – nervous system
• Facts – 20 grams in body
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Manganese (Mn)
• Use – trace element, associated with
many enzymes
• Source – food supply, grains, nuts
• Recommended daily – 2 to 5 mg
• Absorption – intestine poor (5%)
• Toxicity – inhalation – respiratory
disease, nervous system, Parkinson’s like syndrome, psychiatric disorders
• Facts – half-live 37 days
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Selenium (Se)
• Use – essential element, present in
most tissue, anticancer, reduces
toxicity of metal mercury and cadmium
• Source – food supply, shrimp, meat
• Recommended daily – 55-70 µg/day,
not to exceed 200 µg/day
• Absorption – intestine
• Toxicity – deficiency – heart disorders
- excess – “blind staggers”,
neurological effects
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Zinc (Zn)
• Use – essential element, cofactor with
several enzymes, and proteins
• Source – food supply, drinking water
• Recommended daily – 12-25 mg
• Absorption – intestine
• Toxicity – deficiency – impaired
growth, neurological disorders, inhalation can cause metal fume fever
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Toxic Metals
Al
As
Cd
Co
Pb
Hg
Hg-CH3
Ni
Sn
A Small Dose of Toxicology
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Aluminum (Al)
Arsenic (As)
Cadmium (Cd)
Cobalt (Co)
Lead (Pb)
Mercury – Inorganic (Hg)
Mercury – Organic (Hg-CH3)
Nickel (Ni)
Tin (Sn)
A Small Dose of Metals – 04/13/11
Aluminum (Al)
• Use – wide range of consumer
products, airplanes to cans
• Source – food, drinking water
• Absorption – poor
• Toxicity – Dialysis dementia,
possibly neurotoxic
• Facts – non-essential, intake 1-10
mg/day
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Arsenic (As)
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Use – pesticide and herbicide
Source – food, drinking water
Absorption – intestine
Toxicity – cancer, heart, liver,
neurological
• Facts – exists in different states –
trivalent (most common),
pentavalent, arsenic trioxide,
organic and inorganic ...etc…
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Beryllium (Be)
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Use – metal alloy, nuclear power plants
Source – workplace, coal combustion
Absorption – lung, skin
Toxicity – lung, can be delayed and is
progressive, contact dermatitis
probable carcinogen
• Facts – discovered in 1828, more that
1250 tons from oil and coal combustion
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Cadmium (Cd)
• Use – alloy in metal, paint
• Source – shellfish, cigarette smoke, workplace
– welding, paints
• Absorption – intestine, lungs
• Toxicity – lung, emphysema, kidney, calcium
metabolism, possible lung carcinogen
• Facts – “Itai-Itai” is Japanese for “ouch-ouch”
– refers to bone pain related to calcium loss
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Cobalt (Co)
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Use – component of vitamin B12,
Source – alloy in metals, magnets
Recommended daily – none
Absorption – intestine
Toxicity – excessive heart failure,
inhalation – “hard metal” lung disease
• Facts – once used a foaming agent in
beer
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Lead (Pb)
• Use – not essential, batteries, old paint and
previously gasoline, hobbies
• Source – home, paint, dust, kids-hands to
mouth, workplace
• Absorption – intestine (50% kids, 10% adults)
• Toxicity – developmental and nervous system
• Facts – developing nervous system very
sensitive to low levels of exposure
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Inorganic Mercury (Hg)
• Use – consumer products, industry, dental
amalgams, switches, thermometers
• Source – mining, environment
• Absorption – inhalation, intestine poor
• Toxicity – nervous system toxicant, “Mad
Hatters” disease
• Facts – liquid silver evaporates at room
temperature, bacteria convert to organic
methyl mercury (see next slide)
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Organic Mercury (Hg-CH3)
• Use – limited laboratory use - most
common is methyl mercury (Hg-CH3)
• Source – contaminates some fish (e.g.
tuna, shark, pike)
• Absorption – intestine very good (90%)
• Toxicity – nervous system toxicant, and
developmental toxicant
• Facts – bacteria convert inorganic
mercury to methyl mercury then in to
food supply (bioaccumulation)
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Nickel (Ni)
• Use – not essential, metal alloy, stainless
steel
• Source – food supply, jewelry, workplace
• Absorption – intestine, skin
• Toxicity – carcinogen (lung), contact
dermatitis
• Facts – discovered in 1751, 200,000
metric tons used yearly
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Tin (Sn)
• Use – inorganic – consumer products
- organic – fungicide, bactericides
• Source – food packaging
• Absorption – intestine (low inorganic, high
organic)
• Toxicity – inorganic - little
- organic – central nervous system
• Facts – triethyltin and trimethyltin most toxic
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Medically Important
A small group of metals are
used to treat disease
Bi
F
Ga
Au
Li
Pt
A Small Dose of Toxicology
 Bismuth (Bi)
 Fluoride (F)
 Gallium (Ga)
 Gold (Au)
 Lithium (Li)
 Platinum (Pt)
A Small Dose of Metals – 04/13/11
Bismuth (Bi)
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Use – antacids, diarrhea
Source – mining, consumer products
Absorption – intestine
Toxicity – kidney, chronic use results
in range of effects
• Facts – discovered in 1753, used to
treat syphilis and malaria
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Fluoride (F)
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Use – tooth protection
Source – drinking water, food supply
Absorption – intestine
Toxicity – excess causes mottled
teeth enamel (fluorosis)
• Facts – common water level 0.5 to 1.5
ppm, 3 ppm effects teeth
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Gallium (Ga)
• Use – visualization tool for soft
tissues in x-rays
• Source – mining, medical injection
• Absorption – very poor
• Toxicity – kidney
• Facts – liquid at room temperature,
half-life 4 to 5 days
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Gold (Au)
• Use – treat rheumatoid arthritis,
range of industrial uses
• Source – mining, medical injection
• Absorption – poor
• Toxicity – kidney, skin and mouth
lesions
• Facts – long half-life
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Lithium (Li)
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Use – treat psychiatric disorders
Source – food supply, plants & meat
Absorption – intestine
Toxicity – wide range, e.g. tremor,
seizures, slurred speech,
cardiovascular, nausea, vomiting
• Facts – daily intake about 2 mg
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Platinum (Pt)
• Use – anti-cancer agent (cisplatin),
catalytic converters, metal alloy
• Source – mining, road dust
• Absorption – poor, as a drug
intravenous administration
• Toxicity – neuromuscular, kidney
• Facts – inhibits cell division, treat
ovarian & testicular cancer
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Chelation
 Properties
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Metal chelators accelerate the excretion
of metal from the body
Non-specific – can remove essential
metals and elements
Chelate is from the Geek word for claw
 Examples
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BAL – one of the first, broad action but
potentially toxic
Calcium EDTA – lead
Penicillamine – copper
Desferrioxamine – iron
DMPS – lead, mercury
Number of others
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Summary
We can not live without
metals but some require
our utmost respect.
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
A Small Dose of ™ Metal
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Additional Information
 Web Sites
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Health Canada - Nutrition. http://www.hcsc.gc.ca/english/lifestyles/food_nutr.html
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U.S. Agency for Toxic Substance Disease Registry
(ATSDR). http://www.atsdr.cdc.gov/
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Dartmouth Toxic Metals Research Program.
http://www.dartmouth.edu/~toxmetal/HM.shtml The
site has general information on toxic metals.
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11
Authorship Information
This presentation is supplement to
“A Small Dose of Toxicology”
For Additional Information Contact
Steven G. Gilbert, PhD, DABT
E-mail: sgilbert@innd.org
Web: www.asmalldoseof.org
A Small Dose of Toxicology
A Small Dose of Metals – 04/13/11