This document summarizes key concepts about the study of toxins and their adverse effects on living organisms. It discusses what toxins and poisons are, dose-response relationships, routes of exposure, susceptibility factors, and provides examples of acute and chronic toxicity of substances like lead, mercury, and PCBs. It also describes biomagnification in food chains and how PCBs became a widespread global contaminant impacting human and ecosystem health.

2. The study of the adverse effects
of a toxin on living organisms
• Adverse effects
– any change from an organism’s normal state
– dependent upon the concentration of toxin at the target
site for a sufficient time
• Toxin (Poison)
– any agent capable of producing a deleterious response
in a biological system
• Living organism
– a sac of water with target sites, storage depots and
enzymes

3. What is a Poison?
All substances are poisons;
there is none that is not a poison.
The right dose
differentiates a poison and a remedy.
Paracelsus (1493-1541)

4. What is a Dose?
The amount of chemical entering the body
This is usually given as
mg of chemical/kg of body weight = mg/kg
The dose is dependent upon
* The environmental concentration
* The properties of the toxin
* The frequency of exposure
* The length of exposure
* The exposure pathway

5. What is a Response?
• Change from normal state
– could be on the molecular, cellular, organ, or
organism level--the symptoms
• Local vs. Systemic
• Reversible vs. Irreversible
• Immediate vs. Delayed

6. Dose-Response Relationship:
As the dose of a toxin increases,
so does the response.
2
3
4
0 1 DOSE
RESPONSE
0-1 NOEL
2-3 Linear Range
4 Maximum Response
DOSE DETERMINES THE BIOLOGICAL RESPONSE

7. LD50
• Lethal dose in 50% of the animal pop.
tested – death within 14 days
• Expressed in mg/Kg
• Different toxins can be compared-- the
lower the lethal dose, the more acutely toxic

8. LD50 Comparison
Chemical LD50 (mg/kg)
Ethyl Alcohol 10,000
Sodium Chloride 4,000
Ferrous Sulfate 1,500
Morphine Sulfate 900
Strychnine Sulfate 150
Nicotine 1
Black Widow 0.55
Curare 0.50
Rattle Snake 0.24
Dioxin (TCDD) 0.001
Botulinum toxin 0.0001

9. Exposure: Pathway
• air, water, soil, or multiple pathways
• Entry routes: Inhalation (respiratory)
Absorption (dermal)
Ingestion (oral)
Injection (intravenous, intramuscular,
intraperitoneal)
Toxicity will vary depending on the entry route
Ex: ingest mercury- goes right through with little
effect. Inhale fumes- highly toxic.

10. Exposure: Duration
Acute < 24hr usually 1 exposure
Subacute 1 month repeated doses
Subchronic 1-3mo repeated doses
Chronic > 3mo repeated doses
Over time, the amount of chemical in the body can
build up, it can redistribute, or it can overwhelm
repair and removal mechanisms

11. Susceptibility
• Varies by species
– Close taxonomy cannot predict similarity in
susceptibility
• Varies between individuals due to:
– genetics
– age
– health status
– gender
– nutrients
– hormonal status
– synergistic and antagonistic effects

12. Individual Susceptibility
--there can be 10-30 fold difference in
response to a toxicant in a population
• Genetics-species, strain variation, individual
variations (yet still can extrapolate between
mammals--similar biological mechanisms)
• Gender (gasoline nephrotox in male mice only)
• Age--young
– underdeveloped excretory mechanisms
– underdeveloped biotransformation enzymes
– underdeveloped blood-brain barrier

13. Individual Susceptibility
• Age--old
– changes in excretion and metabolism rates,
body fat
• Nutritional status
• Health conditions
• Previous or Concurrent Exposures
– additive --antagonistic
– synergistic

14. Acute toxicity
One-time, large exposure
Ex: acute lead poisoning symptoms:
abdominal pain
acute PCB (and dioxin) poisoning symptoms:
chloracne

15. Chronic toxicity
Repeated exposure, low dose
Ex. Chronic lead poisoning symptoms:
– anemia and nervous system damage
Chronic PCB poisoning symptoms:
– developmental disabilities, birth defects and
endocrine system damage

16. Environmental toxicity
• Compartments:
– Atmosphere
– Hydrosphere
– Lithosphere
– biosphere
• Environmental fate:
– where it goes (biomagnification)
– how it is transformed (biotransformation)
– how long it persists
– where it accumulates (bioaccumulation)

17. Biomagnification:
Toxin becomes more concentrated as it goes up
the food chain:

18. Biotransformation:
Toxin enters a biological system and is chemically
changed, becoming more or less toxic.
inorganic mercury organic methylmercury
Hg HgCH3
methylation

19. Bioaccumulation:
fat-soluble chemicals
accumulate in fatty tissue:
– Liver
– Heart
– Kidney
– Lungs
– breast milk (by 1976- PCBs
in 99% of all US breast
milk)

20. Toxic exposure is not new
• Hippocrates described lead poisoning
in 370 BC
• Mercury fumes killed Roman slaves
and prisoners in Spanish mercury
mines
• Turkish peasants lived in houses built
with asbestos died of lung disease
What is new?

21. We are ALL exposed to toxic
compounds every day
• 1000 new synthetic compounds/yr.
• Many persist though wastewater
treatment and go into waterways,
affecting fish and wildlife
• 70, 000 chemicals in common use in
US, many petroleum distillation
products

22. Petrochemical Products
• Herbicides
• Pesticides
• Antimicrobials
• Anticancer drugs
• Antidepressants
• Anticonvulsants
• Plastics
•
•

23. PCBs
polychlorinated biphenyls
The most widespread chemical contaminant
throughout the global environment.
• 1964- Swedish researchers studying DDT
found EVERY SAMPLE they tested had
high levels of PCBs:
– Fish
– Birds
– Polar bears
– Animals in deep sea trenches

24. History of PCBs:
• 1929-1973: 1.4 billion pounds produced in US
• 1930: began to be sold by Monsanto as “Arachlor”
• 1973: FDA established tolerance levels in food
• 1976: TSCA banned production, sale, distribution
or use in open systems
• 1977: Monsanto terminated production

25. Properties of PCBs:
• High boiling point
• Heat resistant
• Hydrophobic
– Soluble in oil
– Insoluble in water
• Nonconductor

26. Ways PCBs Escape into the
Environment
1. Discharges into waterways
– GE, Outboard Manufacturing
2. Vapor from paint or landfills
3. Fire
– 1981 Binghampton, NY- took years to clean up and cost $37M
4. Leaks in industrial equipment
– 1979, Billings, Montana- millions of lbs. of contam. chicken feed
5. Accidental spills and illegal dumping
– 1978, NC- 210 miles of back roads, 31,000 gallons discharged

27. Health Effects of PCBs
Toxic even at low doses. Studies in rodents, minks
and Rhesus moneys show:
• Liver disorders
• Low birthweight
• Miscarriage
• Liver cancer (in rats)
• Endometriosis (Rhesus monkeys)

28. Mothers who ate fish from Lake
Michigan during pregnancy had
children with:
• Smaller head circumference
• low birth weight
• Less cooperative behavior
• Poor memories
• Lower IQ
Michigan Maternal Infant Cohort Study
1984-1990

29. PCBs are Endocrine Disruptors
along with at least 50 other chemicals including:
• Heavy metals (lead and mercury)
• Many synthetic petroleum based chemicals
including DDT and dioxin
• Plastics containing phthlates (a plastic softening
agent)

30. Endocrine disruptors mimic
human hormones
Endocrine disruptors affect:
• Fetal development
• Sex differentiation
• Reproduction
• The immune system
• Brain development