toxicologi

1. Introduction to Toxicology
Institute For Public Health

2. • Toxicology is the fundamental science of poisons.
• A poison is generally considered to be any
substance that can cause severe injury or death as a
result of a physicochemical interaction with living
tissue. However, all substances are potential poisons
since all of them can cause injury or death following
excessive exposure.
• On the other hand, all chemicals can be used safely
if exposure of people or susceptible organisms to
chemicals

3. Units Used to Measure
Chemicals
in the Environment
• PPM – Parts per million
• PPB – Parts per billion
• PPT – Parts per trillion

4. A simple cube 1 cubic meter
in
volume
1m
1m
1m

5. Is formed of 1,000,000 cubes,
1 cubic centimeter each
100cm
100cm
100cm
100cm x 100cm
x 100cm =
1,000,000cc
In 1 m3
block
1cc = 1ppm

6. One part per million is
• 1 inch in 16 miles
• 1 minute in two years
• 1 cent in $10,000
• 1 ounce of salt in 31 tons of potato
chips
• 1 bad apple in 2,000 barrels of apples

7. Divide each 1cc block into
1,000 blocks 0.1cm on a side
1cm
1cm
1cm
0.1cm x 0.1cm x
0.1cm =
0.001cm3
In 1 m3
block
0.001cm3 =
0.001cc or
1ppb

8. One part per billion is
• 1 inch in 16,000 miles
• 1 second in 32 years
• 1 cent in $10,000,000
• 1 pinch of salt in 10 tons of potato chips
• 1 lob in 1,200,000 tennis matches
• 1 bad apple in 2,000,000 barrels of
apples

9. And divide each 0.1cc block
into 1,000 blocks 0.01cm
on a side
0.1cm
0.1cm
0.1cm
0.01cm x 0.01cm
x 0.01cm =
0.000001cm3
In 1 m3
block .
000,000,001m3 =
0.000,001cc or
1ppt

10. One part per trillion is
• 1 postage stamp in the area of the city of
Dallas
• 1 inch in 16 million miles (more than 600
times around the earth)
• 1 second in 320 centuries
• 1 flea on 360 million elephants
• 1 grain of sugar in an Olympic sized pool
• 1 bad apple in 2 billion barrels

11. Important Concept
• On the left side of the decimal point ( . )
– 1 trillion is bigger than 1 billion
– 1 billion is bigger than 1 million
– 1 million is bigger than 1 thousand…
• On the right side of the decimal point ( . )
– 1 part per trillion is smaller than 1 part per billion
– 1 part per billion is smaller than 1 part per million
– 1 part per million is smaller than 1 part per
thousand

12. Important Relationship
For water at STP (standard temperature
[23o
C] and pressure [15 psi])
1 cc = 1ml = 1g

13. Which means that
1 liter of water = 1 kg
1 mg / kg = 1 ppm
1mm3
/ liter = 1 ppm
1 mg / liter = 1 ppm

14. Measures of Toxicity
• Toxicity of chemicals is determined in the
laboratory
• The normal procedure is to expose test
animals
– By ingestion, application to the skin, by inhalation,
gavage, or some other method which introduces
the material into the body, or
– By placing the test material in the water or air of
the test animals’ environment

15. Measures of Toxicity
• Toxicity is measured as clinical “endpoints”
which include
– Mortality (death)
– Teratogenicity (ability to cause birth defects)
– Carcinogenicity (ability to cause cancer), and,
– Mutagenicity (ability to cause heritible change in
the DNA)
• At this time we will discuss 2 measures of
mortality – the LD50 and the LC50

16. Measures of Toxicity:
The Median Lethal Dose
LD50
The amount (dose) of a chemical which
produces death in 50% of a population of test
animals to which it is administered by any of a
variety of methods
mg/kg
Normally expressed as milligrams of substance
per kilogram of animal body weight

17. CHEMICAL INTERACTIONS
Additive:
• A major problem in assessing the likely effect of
exposure to a chemical is that
• of assessing possible interactions. The simplest
interaction is an additive effect.
• this is an effect, which is the result of two or more
chemicals acting together and is
• the simple sum of their effects when acting
independently. In mathematical terms,
• 1 + 1 = 2, 1+ 5 = 6, etc.
• The effects of organochlorine pesticides are usually
additive.

18. Synergistic
• More complex is a synergistic
(multiplicative) effect: this is an effect of
two chemicals acting together, which is
greater than the simple sum of their
effects when acting alone; it may be
called synergism. In mathematical
terms,
• 1 + 1= 4, 1+ 5 = 10, etc.

19. Potentiation
• Another possible form of interaction is
potentiation. In potentiation, a
substance that on its own causes no
harm makes the effects of another
chemical much worse.
• This may be considered to be a form of
synergism. In mathematical terms,
• 0 + 1 = 5, 0 + 5 = 20, etc.

20. Antagonism
• The opposite of synergism is antagonism: an
antagonistic effect is the result of a chemical
counteracting the adverse effect of another;
in other words, the situation where exposure
to two chemicals together has less effect than
the simple sum of their independent effects.
Such chemicals are said to show antagonism.
In mathematical terms,
• 1 + 1 = 0, 1+ 5 = 2, etc.

21. Measures of Toxicity:
The Median Lethal
Concentration
LC50
The concentration of a chemical in an
environment (generally air or water) which
produces death in 50% of an exposed
population of test animals in a specified time
frame
mg/L
Normally expressed as milligrams of substance
per liter of air or water (or as ppm)

22. Primary Routes of Exposure
to Pesticides
There are three primary routes by which
organisms are exposed to pesticides
Oral
Dermal
Inhalation

23. Primary Routes of Exposure:
Oral Exposure
Any exposure to pesticide which occurs when
the chemical is taken in through the mouth
and passes through the gastrointestinal tract
During oral exposure, although carried within
the body, the pesticide is still outside of the
body cavity

24. Primary Routes of Exposure:
Dermal Exposure
Exposure of the skin to a pesticide
Most common route of human exposure
With proper hygiene this type of exposure is
generally not serious unless there is a
specific, rapid toxicological effect (often eye
effects) which is of concern

25. Primary Routes of Exposure:
Inhalation Exposure
Occurs when a pesticide is breathed into the
lungs through the nose or mouth
Significant route of exposure for aquatic
organisms
Not of toxicological concern until it crosses from
the lung into the body (unless the chemical is
corrosive)

26. Duration of Exposure
Three terms are commonly used to
describe the duration of dose(s)
Acute
Chronic
Subchronic

27. Duration of Exposure:
Acute Exposure
Application of a single or short-term
(generally less than a day) dosing by a
chemical
If toxic symptoms are expressed, they are
referred to as symptoms of “acute
toxicity”

28. Duration of Exposure:
Chronic Exposure
Expression of toxic symptoms only after
repeated exposure to a chemical in doses
regularly applied to the organism for a time
greater than half of its life-expectancy
If toxic symptoms are expressed, they are
referred to as symptoms of “chronic toxicity”

29. Duration of Exposure:
Subchronic Exposure
Toxic symptoms are expressed after repeated
applications for a timeframe less than half the
life expectancy of the organism – but more
often than a single dose or multiple doses
applied for only a short time
If toxic symptoms are expressed, they are
referred to as symptoms of “subchronic
toxicity”

30. Remember –
• For pesticides – less is more when
dealing with toxicity
• The less you need to cause a toxic
effect – the more toxic the substance is
• Thus an LD50 of 25 mg/kg is more toxic
than is one of 7,000 mg/kg

31. Words again
Safe
Low Risk

32. Signal Words
The relative acute toxicity of a pesticide is
reflected on the label in the form of a “signal
word”
The (toxicologically) appropriate signal word
MUST appear on every pesticide label
The three possible signal words are
CAUTION
WARNING
DANGER

33. Signal Words:
CAUTION
“Caution” reflects the lowest degree of relative
toxicity
All pesticides with an LD50 of greater than 500
mg/kg must display this word on their label
Actually includes two groups of pesticides –
those classed by the EPA as “Relatively
nontoxic (>5,000 mg/kg) and those classed
as “slightly toxic” (500 – 5,000 mg/kg)

34. Signal Words:
WARNING
“Warning” reflects an intermediate degree
of relative toxicity
All pesticides with an LD50 of greater than
50 and less than 500 mg/kg must
display this word on their label
Pesticides in this category are classed as
“moderately toxic”

35. Signal Words:
DANGER
“Danger” reflects the highest degree of relative
toxicity
All pesticides with an LD50 of less than 50
mg/kg must display this word on their label
Pesticides here are classed as “highly toxic”

36. POISON!!!
• Legally defined term – not just anything you
don’t like
• Any pesticide with an LD50 of 50 mg/kg or less
• Labels must reflect this classification
• Label must have the signal word “DANGER”
plus the word “POISON”
• Label also must display the skull and
crossbones icon

37. Relative toxicity
• Organisms can’t differentiate between
“natural” and “synthetic” chemicals
• “Synthetic” does not mean toxic or poisonous
• “Natural” does not mean safe or even low risk
• Chemicals must be evaluated in their
biological context of behavior in organisms
• Mode of action, not source, is the concern of
toxicologists and informed users of pesticides

38. Relative toxicity
• Most herbicides act on biological pathways
not present in humans
• Those approved for use in the Region (much
more about these later!!) have LD50s of 50
mg/kg or greater – they have intermediate or
relatively low toxicity
• Some of the insecticides used are highly
toxic

39. Relative toxicity
• Some examples of pesticides and other
chemicals are given to show relative risk of
pesticides in the environment in which we live
• This is NOT to trivialize the pesticides
• Always treat them with caution and respect
• But, have a realistic recognition of their
relative risk in a world of risks

40. Relative toxicity:
Insecticides
• TCDD (Dioxin) 0.1 mg/kg
• Parathion 13.0 mg/kg
• Nicotine 50.0 mg/kg
• Carbaryl 270.0 mg.kg
• Malathion 370.0 mg/kg

41. Relative Toxicity:
Herbicides and Additives
mg/kg
Paraquat 95
2,4-D 375
2,4-DP 532
Triclopyr 630
Tebuthiuron 644
Dicamba 757
Hexazinone 1,690
Glyphosate 4,320
mg/kg
Limonene 5,000
Clopyralid >5,000
Sulfometuron Met.. >5,000
Imazapyr >5,000
Diesel oil 7,380
Picloram 8,200
Fosamine am.. 24,400
Kerosene 28,000

42. Relative Toxicity:
Comparative information
Highly toxic chemicals
0 – 50 mg/kg range
(taste 1 teaspoonful)
mg/kg
• Botulinus toxin 0.00001
• Dioxin 0.1
• Parathion 13.0
• Strychnine 30.0
• Nicotine 50.0
Moderately toxic chemicals
50- - 500 mg/kg range
(teaspoonful 1 ounce)
mg/kg
• Paraquat 95
• Caffeine 200
• Carbaryl 270
• Malathion 370
• 2,4-D 375

43. Relative Toxicity
Comparative Information
Slightly toxic chemicals
500 – 5,000 mg/kg range
(1 ounce 1 pint)
mg/kg
• 2,4-DP 532
• Triclpoyr 630
• Tebuthiuron 644
• Dicamba 757
mg/kg
• Formaldehyde 800
• Hexazinone 1,690
• Asprin 1,700
• Vitamin B3 1,700
• Household bleach 2,000
• Table salt 3,750
• Glyphosate 4,320
etc.

44. Relative Toxicity:
Are all substances toxic?
YES!
 All are toxic to some quantifiable degree
 Sugar has an LD50 of 30,000 mg/kg
 The foresters favorite – ethanol has an LD50 of
only 13,700 mg/kg
 Even water has a recognized LD50 of slightly
greater than 80,000 mg/kg

45. Relative Toxicity:
The Last Word
 Pesticides are chemicals introduced into the
environment to perform a function
 The source of a chemical (synthetic vs.
natural) is irrelevant when considering its
toxicity
 Pesticides should be treated with care and
proper respect – but so should household
cleaners, gasoline and kerosene, bleaches,
paints and all other chemicals