Download Chromium

Heavy Metal Toxicity
H.R.Sarreshtahdar, MD
Occupational Medicine Specialist
Arsenic
Lead
Mercury
HEAVY METALS
The term heavy metal refers to any metallic chemical
element that has a relatively high density and is
toxic or poisonous at low concentrations.
HEAVY METALS
• Are natural components of the Earth's crust
• To a small extent they enter our bodies via food, drinking
water and air
• As trace elements, some heavy metals (e.g. copper,
selenium, zinc) are essential to maintain the metabolism
of the human body however, at higher concentrations
they can lead to poisoning
• Heavy metal poisoning could result, for instance, from
drinking-water contamination (e.g. lead pipes), high
ambient air concentrations near emission sources, or
intake via the food chain
Mercury - Hg
Mercury is the only common metal which is liquid
at ordinary temperatures. It rarely occurs free in
nature and is found mainly in cinnabar ore (HgS)
in Spain and Italy.
It alloys easily with many metals, such as gold,
silver, and tin - these alloys are called amalgams.
Its ease in amalgamating with gold is used in the
recovery of gold from its ores.
Health effects of mercury
• Disruption of the nervous system
• Damage to brain functions
• DNA damage and chromosomal damage
• Allergic reactions, resulting in skin rashes,
• Tiredness and headaches
• Negative reproductive effects, such as sperm damage,
birth defects and miscarriages
Environmental effects of mercury
• Fish are organisms that absorb great amounts of
methyl mercury from surface waters every day
(mercury can accumulate in fish and in the food
chains)
• The effects that mercury has on animals are:
kidneys damage, stomach disruption, damage to
intestines, reproductive failure and DNA
alteration
What is Cadmium?
• A metal most often encountered in earth’s crust
combined with chlorine (cadmium chloride), oxygen
(cadmium oxide), or sulfur (cadmium sulfide)
• Exists as small particles in air, result of smelting, soldering
or other high temp. industrial processes
• By-product of smelting of zinc, lead, copper ores
• Used mainly in metal plating, producing
pigments, batteries, plastics and as a
neutron absorbent in nuclear reactors
Cadmium is used in batteries
Cadmium and Smelters/Mine
Sites
• Cadmium is a by-product of smelters
• Has been a concern at the Summitville mine site in
Colorado
Photo of Smelter
Exposure Sources - Tobacco
• Tobacco smoke (a one pack a day smoker absorbs roughly
5 to 10 times the amount absorbed from the average daily
diet)
Tobacco smoke is an
important source of
cadmium exposure
Exposure Sources – By Mouth
• Foods (only a small amount is absorbed)
• Itai Itai disease (cadmium contamination + diet low in
calcium & vitamin D)
Cadmium – Cd
HEALTH EFFECTS
• Human uptake of cadmium takes place mainly
through food
• Foodstuffs that are rich in cadmium can greatly
increase the cadmium concentration in human
bodies (liver, mushrooms, shellfish, mussels,
cocoa powder and dried seaweed)
Why Is Cadmium a Health Hazard?
• Affects lungs & kidneys
• 2o effects on skeletal system
• Binds to sulfhydryl groups, displacing other metals from
metalloenzymes, disrupting those enzymes
• Competes with calcium for binding sites on regulatory
proteins
Respiratory Effects
• Acute inhalation may mimic metal fume fever
• Fever, chills & decreases in FVC and FEV1
Initial symptoms: flu-like symptoms
• Later: chest pain, cough, dyspnea
• Bronchospasm and hemoptysis may occur
• Chronic inhalation MAY result in impairment of
pulmonary function with reduction in ventilatory
capacity
Renal Effects
• May cause tubular and glomerular damage
with resultant proteinuria
• May follow chronic inhalation or ingestion
• Latency period of ~10 yrs
• Nephropathy is progressive & irreversible
Renal Effects
• Chronic exposure – progressive renal tubular
dysfunction
• Toxic effects are dose related
• Critical renal concentration
• Decreased GFR
• Chronic renal failure
• Kidney stones more common
Skeletal Effects
• Bone lesions occur late in severe chronic
poisoning
• Pseudofractures
• Other effects of osteomalacia and osteoporosis
• Appear to be secondary to increased urinary
calcium and phosphorus losses
Signs and Symptoms - Acute
• Food poisoning (ingestion)
• Bronchitis (inhalation)
• Interstitial pneumonitis (inhalation)
• Pulmonary edema (inhalation)
• A condition that mimics metal fume fever
Children who eat dirt
(pica behavior) are at risk
Signs & Symptoms - Chronic
• Chronic exposure may result in renal dysfunction and bone
disease
• Mild anemia, anosmia & yellow discoloration of the teeth may
occur
Chronic exposure may effect
the sense of smell
HEALTH EFFECTS
• Diarrhoea, stomach pains and severe vomiting
• Bone fracture
• Reproductive failure and possibly even
infertility
• Damage to the central nervous system
• Damage to the immune system
• Psychological disorders
• Possibly DNA damage or cancer development
Chromium - Cr
• Chromium(III) is an essential nutrient for
humans and shortages may cause heart
conditions, disruptions of metabolisms and
diabetes
• But the uptake of too much chromium(III) can
cause health effects as well, for instance skin
rashes
Chromium - Cr
Chromium(VI) is a danger to human health,
mainly for people who work in the steel and
textile industry
People who smoke tobacco also have a higher
chance of exposure to chromium
Hexavalent Chromium – Chromium (VI) is a
species of chromium that is forbidden to use in
electrical & electronic industry.
HEALTH EFFECTS
• When it is a compound in leather products, it can
cause allergic reactions, such as skin rash
• After breathing it in, chromium(VI) can cause nose
irritations and nosebleeds
• Upset stomachs and ulcers
• Respiratory problems
• Weakened immune system
• Kidney and liver damage
• Alteration of genetic material
• Lung cancer
• Death
Environmental effects of chromium
• Chromium(III) is an essential element for
organisms that can disrupt the sugar
metabolism and cause heart conditions, when
the daily dose is too low
• Chromium(VI) is mainly toxic to organisms - it
can alter genetic materials and cause cancer
Lead - Pb
• Foods such as fruit, vegetables, meats, grains,
seafood, soft drinks and wine may contain
significant amounts of lead
• Cigarette smoke also contains small amounts of
lead
Lead sources
• application of lead in gasoline
• fuel combustion
• industrial processes
• solid waste combustion
Lead Paint
• The use of lead in residential paint was banned
in 1977
• Lead-containing pigments still are used for
outdoor paint products because of their bright
colors and weather resistant properties
• Tetraethyl and tetramethyl lead are still used as
additives in gasoline in several countries
ToxicoKinetics and ToxicoDynamics
• Absorption:
• Lungs: depends on size particle
• GI:
• Adults: 20-30%
• Children: as much as 50% of dietary lead
• Inadequate intake of iron, calcium, and total
calories are associated with higher lead levels
• Skin:
• Inorganic lead is not absorbed
• Organic lead is well absorbed
• Lead is carried bound to the RBC
PharmacoKinetics and PharmacoDynamics
• Distributed extensively throughout tissues: bone, teeth,
liver, lung, kidney, brain, and spleen
• Body lead storage: bones- can constitute a source of
remobilization and continued toxicity after the
exposure has ceased
• Lead crosses the BBB and concentrates in the gray
matter
• Lead crosses the placenta
• Excretion:
• Kidneys. The excretion increases with increasing body
stores (30g-200 g/day)
• Feces
Signs and Symptoms of Lead Toxicity
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Fatigue
Irritability
Lethargy
Paresthesis
Myalgias
Abdominal pain
Tremor
Headache
Vomiting
Weight loss
Constipation
Loss of libido
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Motor neuropathy
Encephalopathy
Cerebral edema
Seizures
Coma
Severe abdominal
cramping
• Epiphyseal lead lines in
children (growth arrest)
• Renal failure
Range of Lead-induced Health Effects in
Adults and Children
Blood lead
levels
Adults
Children
10 g/dL
Hypertension may occur
•Crosses placenta
•Impairment IQ, growth
•Partial inhibition of heme synthesis
20 g/dL
Inhibition of heme
synthesis
Increased erythrocyte
protoporphyrin
Beginning impairment of nerve
conduction velocity
30 g/dL
•Systolic hypertension
•Impaired hearing()
Impaired vitamin D metabolism
40 g/dL
•Infertility in males
•Renal effects
•Neuropathy
•Fatigue, headache, abd
pain
Hemoglobin synthesis inhibition
50 g/dL
Anemia, GI sx, headache,
tremor
Colicky abd pain, neuropathy
100 g/dL
Lethargy, seizures,
encephalopathy
Encephalopathy, anemia, nephropathy,
seizures
Health effects of lead
• Disruption of the biosynthesis of haemoglobin and
anemia
• A rise in blood pressure
• Kidney damage
• Miscarriages
• Disruption of nervous systems
• Brain damage
• Declined fertility of men through sperm damage
• Diminished learning abilities of children
• Behavioural disruptions of children, such as
aggression, impulsive behaviour and hyperactivity
Health effects of lead
• Lead can enter a foetus through the placenta of
the mother
• Because of this it can cause serious damage to
the nervous system and the brains of unborn
children
That is why women in pregnancy can not work
with lead.
• The average lead level of American
children is 2 g/dl
• 8.9% of American children have lead
poisoning
• Lead intoxication is more prevalent in
minority groups and among those living in
the northeast
Diagnosis
• Evaluation of clinical symptoms and signs
• CBC
• Serum iron levels, TIBC, ferritin
• Abdominal radiographs (for recent ingestion of
lead-containing material)
• Whole blood lead level
• X-ray fluorescence (XRF)- to asses body burden
Arsenic
Introduction
• Commercial products
• Wood preservatives
• Pesticides
• Herbicides
• Fungicides
• Food
• Seafood and fish
• Others
• Antiparasitic drugs
Toxicokinetics
• T1/2 of inorganic arsenic in the blood is 10 hrs
and of organic arsenic is around 30 hours
• 2-4 weeks after the exposure ceases, most of
the remaining arsenic in the body is found in
keratin-rich tissues (nails, hair, skin)
Toxicokinetics
• Inorganic arsenic is converted to organic arsenic
(biomethylation to monomethyl arsonic- MMA
or DMA) in the liver. This may represent a
process of detoxification
• Renally excreted (30-50% of inorganic arsenic is
excreted in about 3 days). Both forms are
excreted depend on the acuteness of the
exposure and dose
Manifestations of acute arsenic poisoning
Bodily system
affected
Symptoms or signs
Time of onset
Systemic
Thirst
Hypovolemia, Hypotension
Minutes
Minutes to hours
Gastrointestinal
Garlic or metallic taste
Burning mucosa
Nausea and vomiting
Diarrhea
Abdominal pain
Hematemesis
Hematochezia, melena
Rice-water stools
Immediate
Immediate
Minutes
Minutes to hours
Minutes to hours
Minutes to hours
Hours
Hours
Hematopoietic
system
Hemolysis
Hematuria
Lymphopenia
Pancytopenia
Minutes to hours
Minutes to hours
Several weeks
Several weeks
Pulmonary
(primarily in
inhalational
exposures)
Cough
Dyspnea
Chest Pain
Pulmonary edema
Immediate
Minutes to hours
Minutes to hours
Minutes to hours
Liver
Jaundice
Fatty degeneration
Central necrosis
Days
Days
Days
Kidneys
Proteinuria
Hematuria
Acute renal failure
Hours to days
Hours to days
Hours to days
PALMAR KERATOSIS
Biological Monitoring
• Urinary arsenic measurement
• Spot sample (mcg/L)
• Timed urine collection (mcg/24 hours)
• Normal values
• Spot urine= ~10 mcg/L (10-150 mcg/L)
• 24 hours urine collection=<25 mcg/24 hours
• Whole blood= <1mcg/L (usually is elevated in
acute intoxication)
Chromium
• Anerobic (reducing) conditions Cr exists the +3 ion;
not very toxic or soluble under basic neutral or even
acidic conditions
Env. Chemistry, Baird & Cann
• Common oxidation states Cr+3 & Cr+6, in aerobic
conditions Cr exists primarily as the chromate ion –
highly soluble, toxic, can dimerize to dichromate
• Used for electroplating, corrosion resistance &
tanning
• Second most abundant inorganic contaminant of
groundwater under hazardous waste sites
• MCL in US 100 ppb
• Removal –most heavy metals increase the pH but
Cr+6 soluble at any pH but Cr+3 low solubility so Cr+6
usually reduced to +3
Env. Chemistry, Baird & Cann
Cr Contamination of Water