Agriculture Heavy Metal Toxicity

1. Heavy Metal Toxicity

2. Mechanism of Action
• Most common route of exposure is oral
– secondary is inhalation of fumes
• Toxicity is expressed biologically because
of their ability to bind to one or more
ligands of biologic enzyme systems which
then inactivates the enzyme system

3. One of the few poisons that we
have a chemical antidote for:

4. Chelating Agents
• Chemical antidotes - chemically inactivate the
poison
• Compete with enzyme systems for the metals
• Reverse the metals toxic effects
• Enhance the excretion of the metal
• The chelate formed is a stable compound
• Chelates are water soluble
• Chelates are excreted by the kidneys

5. Chelating Agents, cont.
How effective these chelating agents are
depends upon:
• 1) the affinity of the chelator for the metal
• 2) distribution of the chelator to the parts of the
body where the metal is
• 3) ability of the chelator to mobilize the metal
from the body once the chelate is formed

6. Chelating Agents, cont.
Properties of the ideal chelating agent:
• 1) greater affinity for the metal than for ligands of
tissues
• 2) high water solubility
• 3) can penetrate into tissues
• 4) resistant to metabolic degradation by the body
• 5) forms a tight stable bond with the metal which
is non toxic to the body

7. Chelating Agents, cont.
Properties of the ideal chelating agent, cont.
• 6) be readily excreted unchanged
• 7) low affinity for calcium
• 8) minimal inherent toxicity
• 9) be absorbed readily when given orally

8. Chelating Agents, cont.
• No drug has a single effect,
drugs are two edged swords.
• Examples of a chelating agent:
– calcium disodium EDTA - can cause renal
problems, fever, dermatitis, used to treat lead
toxicity

9. Heavy Metals

10. Heavy Metal Toxicity
• Uncommon yet clinically significant condition yet if
unrecognized can be fatal
• Lead is most significant of the heavy metals
• Study by National Health and Nutrition Examination
Survey found that 0.4& of people aged 1 year and older
had blood levels of lead of 25mcg/dL or higher.
• Higher incidence in African Americans
• History is the most critical aspect in diagnosing
• Children absorb more from the GIT than do adults
(50% verses 10%) and childhood plumbism affects
more than 2 million preschoolers

11. Lead toxicity
• The fall of the Roman empire was due to the fact they
used lead for pipes to carry water and for drinking
goblets and utensils.
• Sources - used in the past in medicines (sugar of lead),
insecticides, pesticides, gasoline (tetraethyl lead),
batteries, paints, manufacturing, automobile exhaust.
• Lead poisoning is probably the most important
chronic environmental illness affecting modern
children.
• The organ of greatest concern is the developing brain
which last well into early adulthood.

12. Lead toxicity
• Mortality today is rare.
• Mounting evidence suggests that lead poisoning in
children produces long term problems with
learning, intelligence and earning power.
• Adults with lead poisoning have problems with
depression, aggressive behavior and antisocial
behavior.
• Males with lead poisoning have lower sperm
counts, women have an increase in miscarriages
and smaller babies

13. Lead Toxicity, cont.
Clinical features, plumbism:
Acute intoxication: not common
• colic
• metallic taste to mouth
• vomiting, diarrhea or constipation
• increased thirst
• hemolysis, hemoglobinuria
• oliguria
• paresis and paresthesias

14. Lead Toxicity, cont.
Chronic lead intoxication - much more common
• Burtonian line - dark gray bluish black line on the
gingival margin (H2S + Pb = PbS)
• Basophilic stippling (clumping of RNA)
• Anemia
• Colic, diarrhea, vomiting
• Skeletal muscle weakness
• Increase uric acid in blood
• Headache, confusion, insomnia
• Lead palsy (wrist drop and foot drop)

15. Lead Toxicity, cont.
• Consider lead poisoning whenever a small child
presents with peculiar symptoms that do not match any
one particular disease entity.
• Especially:
– irritability
– sleeplessness
– poor appetite
– headaches
– if parents use folk remedies or their parents work in a lead-
related occupation

16. Lead Toxicity, cont.
Patient management:
• Acute intoxication - induce vomiting,
give cathartics, give proteins to delay
absorption (milk, egg whites),
chelating agents
• Chronic toxicity - give chelating agents

17. Iron Toxicity
• Seen mostly in children, 40, 000 exposures/yr.
• Toxic doses:
– 20-60 mg/kg of elemental iron is potentially toxic
– 60-120 mg/kg is toxic but not usually fatal
– > 120 mg/kg is potentially fatal
• Only 10% of ingested iron is absorbed
• Most iron tablets contain 10-30% elemental
iron by weight

18. Iron Toxicity, cont.
• Sources - dietary supplements
Clinical features:
• toxicity develops when serum iron levels exceed the
iron binding capacity of transferrin in the blood
• body is poorly equipped to handle excessive amounts of
iron - can eliminate only very small amounts/day
• free iron damages tissues by direct corrosive effects,
free iron is a potent vasodilators, directly injures blood
vessels, causes hepatocellualr death, coagulation
disturbances, and metabolic acidosis

19. Iron Toxicity, cont.
Clinical presentation of acute toxicity- 4 Stages
• Stage I - 30 min. to 6 hrs. post ingestion
Acute GI corrosive effects of iron, nausea,
abdominal pain, vomiting, and diarrhea,
hematemesis, hematochezia and melena.
Most patients with mild to moderate toxicity do not
progress beyond this phase.
• Stage II - 6-24 hours post ingestion
sometimes called the latent or quiescent period
transient resolution of patient’s GI signs

20. Iron Toxicity, cont.
• Stage III - 12-48 hours post ingestion
recurrence of GI hemorrhage, hematemesis,
melena and bowel perforation may be seen
acute circulatory shock, metabolic acidosis,
respiratory distress syndrome
death is common is this stage
• Stage IV - 4-6 weeks post ingestion
gastric outlet obstruction or pyloric stenosis as
a result of gastric scarring, vomiting

21. Iron Toxicity, cont.
Chronic toxicity:
• pigmented hepatic cirrhosis, diabetes mellitus,
hyperpigmentation of the skin, hemosiderosis
• hemochromatosis
Treatment:
• induce vomiting
• activated charcoal is of no value
• transport
• chelators

22. Mercury Toxicity
• Hg (Gr. - hydrargyros - water silver)
• Used throughout the centuries, as early as 1500
BC in Egypt
• Drugs (antisyphilitic agents (18th century),
diuretics, cathartics, topical salves), batteries,
paint, shell fish, neon lamps, thermometers,
industry (“mad as a hatter”, 1800’s), BP cuffs,
wood preservatives
• Dental amalgam fillings (50% mercury, 35%
silver, 13% tin, 2% copper with a trace of zinc)

23. Mercury Toxicity
• 1998 AAPCC documented 4039 exposures
• Of these 1039 were in children > 6 years and
1385 in persons > 19years, with 3 deaths.
• Mercury toxicity is usually misdiagnosed because
of the insidious onset, nonspecific signs and
symptoms, and lack of knowledge by medical
profession.

24. Mercury Toxicity, cont.
• Recent environmental exposures:
– 1960 Minamata Bay, Japan
– Mercury contaminated fish in Canada
– Methylmercury treated grain in Iraq (1970) and in US 1996
– Beauty cream products from Mexico.
– Mercury contamination of tuna - currently a problem
– prior to 1990 many paints contained mercury as an anti
mildew agent

25. Mercury Toxicity, cont.
• Only metal which is liquid at room temp.
• Exists in nature in 3 major forms: Mercury in any form
is toxic - difference lies in how it is absorbed, signs and
symptoms, and response to treatment.
– organic (methyl mercury)
– mecuric salts - is highly toxic and corrosive
– elemental - as a vapor can penetrate the CNS
• All forms of mercury are toxic to the fetus, but
methylmercury most readily passes through the placenta
and maternal exposure can lead to spontaneous abortion
or retardation.

26. Mercury Toxicity, cont.
Elemental mercury - quicksilver
• Vaporizes easily at room temperature
• Causes: amalgams, manometers, thermometers, etc.
• 80% absorbed through inhalation, not absorbed well by
GIT.
• Lipid soluble and passes rapidly into blood stream
• See acute pulmonary symptoms, fever, chills, dyspnea,
lethargy, confusion, (in elderly can be misdiagnosed as
Parkinson or Alzheimer’s disease).
• Recovery is usually without sequela.
• Treatment: ABC’s, O2, chelation

27. Mercury Toxicity, cont.
Inorganic mercury - mercurial salts
• route of exposure - oral and GIT
• source - disc batteries, mercurous chloride
• clinical signs associated with the corrosive effects
• signs and symptoms - ashen gray mucous membranes
secondary to ppt. of mecuric salts, severe abdominal
pain, vomiting, hematemesis, shock, loosening of teeth,
renal tubular necrosis.
• Treatment: ABC’s, chelation therapy

28. Mercury Toxicity, cont.
Organic Mercury - methyl mercury
• Usually results from ingestion of contaminated food
• Onset of symptoms usually delayed for days to weeks
post exposure
• Targets enzymes and depletion of these enzymes must
occur before the onset of symptoms
• Clinically see: visual disturbances, ataxia, hearing loss,
mental deterioration, muscles tremors, paralysis and
even death.

29. Mercury Toxicity, cont.
• Thimerosal - an organic mercurial compound used
as a preservative in vaccines to prevent bacterial
contamination - found in diptheria-tetanus-whole
cell pertussis (DTP), Haemophilus influenzae
(HIB), and hepatitis B vaccines.
• July 7, 1999 - American Academy of Pediatrics
and the US Public Health service issued an alert
concerning thimerosal.

30. Mercury Toxicity, cont.
Diagnosis is based on:
• patient history and clinical signs
• urinary levels of mercury (values greater
than 20-25 ug/L is abnormal)
Treatment:
• acute therapy - same as any poison
• chronic - chelation therapy (BAL)

31. Arsenic Toxicity
• Commonly found throughout the earth’s crust in the
metallic state, contaminates well water
• Used in manufacture of herbicides, rodenticides
(arsenic trioxide), and glass and semiconductors
• Tasteless and resembles sugar
• Has been used as a therapeutic agent and as a poison for
more than 2000 years
• Used as a poison for political assassinations; speculated
that Napoleon was poisoned with arsenic

32. Arsenic Toxicity
• 1998 - 956 non pesticide related arsenic exposures
with 4 fatalities; 400 arsenic containing pesticide
exposures with no fatalities
• Arsenic exposure is usually suicidal, homicidal or
occupational
• Most exposures are accidental and deaths are very
rare

33. Arsenic Toxicity, cont.
Mechanism of action:
• Inhibition of sulfhydryl group-containing cellular
enzymes and the replacement of phosphate molecules
in “high energy” compounds
• Trivalent arsenic is a carcinogen (lung and skin cancer)
and is the most toxic form
• Toxic dose ranges from 1 mg to 10 grams
• Can be recovered from the hair, nails and skin

34. Arsenic Toxicity, cont.
Clinical presentation:
• Acute exposure
– burning of the mouth and throat, nausea,
vomiting, profuse diarrhea (rice water
stool), garlic like odor to breath,
increased capillary permeability, shock,
renal damage

35. Arsenic Toxicity, cont.
Chronic toxicity:
• skin pigmentation changes, palmar and plantar
hyperkeratosis
• anorexia, GI symptoms
• anemia (see pale patient with areas of increased
pigmentation and hyperemia - “Milk and Roses”
complexion)
• Mee’s lines (white transverse bands in the nails)
• metallic taste to the mouth
• gangrene of the feet (“blackfoot disease”)
• encephalopathy

36. Arsenic Toxicity, cont.
Diagnosis:
• Urine sample provide the most reliable diagnostic
testing, >200ug/L are abnormal
– use of hair or nails is generally not useful in
evaluating individual patients
Treatment:
• provide support to airway, breathing and circulation
• chelation therapy

37. Natural Chelators
• Chlorella (from algae) is a natural immune
stimulant and has a high affinity for heavy
metals (it contains sulfur bound amino acids
and acts as a natural chelator)
• Garlic and cilantro (Chinese parsley) aid in
the removal of heavy metals