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8/8/2019 03. Toxicology - General
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Introduction to Toxicology
A Brief Introduction to theConcepts of Toxicology
We Will Be UsingThroughout This Course
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Units Used to Measure
Chemicalsin the Environment
PPM Parts per million
PPB Parts per billion
PPT Parts per trillion
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A simple cube 1 cubic meter
involume
1m
1m
1m
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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 block1cc = 1ppm
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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 potatochips
1 bad apple in 2,000 barrels of apples
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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 or1ppb
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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
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And divide each 0.1cc block
into 1,000 blocks 0.01cmon 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 or1ppt
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One part per trillion is
1 postage stamp in the area of the city ofDallas
1 inch in 16 million miles (more than 600times 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
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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 perthousand
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Important Relationship
For water at STP (standard temperature[23oC] and pressure [15 psi])
1 cc = 1ml = 1g
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Which means that
1 liter of water = 1 kg
1 mg / kg = 1 ppm
1mm3 / liter = 1 ppm
1 mg / liter = 1 ppm
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Measures of Toxicity
Toxicity of chemicals is determined in thelaboratory
The normal procedure is to expose testanimals
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
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Measures of Toxicity
Toxicity is measured as clinical endpointswhich 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 ofmortality the LD50 and the LC50
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Measures of Toxicity:
The Median Lethal Dose
LD50
The amount (dose) of a chemical whichproduces death in 50% of a population of testanimals to which it is administered by any of a
variety of methods
mg/kg
Normally expressed as milligrams of substanceper kilogram of animal body weight
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Measures of Toxicity:
The Median LethalConcentration
LC50
The concentration of a chemical in anenvironment (generally air or water) which
produces death in 50% of an exposedpopulation 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)
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Primary Routes of Exposure
to PesticidesThere are three primary routes by which
organisms are exposed to pesticides
Oral
Dermal
Inhalation
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Primary Routes of Exposure:
Oral Exposure
Any exposure to pesticide which occurs when
the chemical is taken in through the mouthand passes through the gastrointestinal tract
During oral exposure, although carried withinthe body, the pesticide is still outside of thebody cavity
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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 isgenerally not serious unless there is aspecific, rapid toxicological effect (often eyeeffects) which is of concern
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Primary Routes of Exposure:
Inhalation ExposureOccurs when a pesticide is breathed into the
lungs through the nose or mouth
Significant route of exposure for aquaticorganisms
Not of toxicological concern until it crosses fromthe lung into the body (unless the chemical iscorrosive)
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Duration of Exposure
Three terms are commonly used todescribe the duration of dose(s)
Acute
Chronic
Subchronic
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Duration of Exposure:
Acute Exposure
Application of a single or short-term
(generally less than a day) dosing by achemical
If toxic symptoms are expressed, they arereferred to as symptoms of acutetoxicity
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Duration of Exposure:
Chronic Exposure
Expression of toxic symptoms only after
repeated exposure to a chemical in dosesregularly applied to the organism for a timegreater than half of its life-expectancy
If toxic symptoms are expressed, they arereferred to as symptoms of chronic toxicity
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Duration of Exposure:
Subchronic Exposure
Toxic symptoms are expressed after repeated
applications for a timeframe less than half thelife expectancy of the organism but moreoften than a single dose or multiple dosesapplied for only a short time
If toxic symptoms are expressed, they arereferred to as symptoms of subchronictoxicity
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Remember
For pesticides less is more whendealing with toxicity
The less you need to cause a toxiceffect the more toxic the substance is
Thus an LD50 of 25 mg/kg is more toxic
than is one of 7,000 mg/kg
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Words again
Safe
Low Risk
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Signal Words
The relative acute toxicity of a pesticide isreflected on the label in the form of a signal
word
The (toxicologically) appropriate signal wordMUST appear on every pesticide label
The three possible signal words areCAUTION
WARNING
DANGER
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Signal Words:
CAUTIONCaution reflects the lowest degree of relative
toxicity
All pesticides with an LD50 of greater than 500mg/kg must display this word on their label
Actually includes two groups of pesticides those classed by the EPA as Relativelynontoxic (>5,000 mg/kg) and those classedas slightly toxic (500 5,000 mg/kg)
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Signal Words:
WARNING
Warning reflects an intermediate degree
of relative toxicityAll pesticides with an LD50 of greater than
50 and less than 500 mg/kg must
display this word on their labelPesticides in this category are classed asmoderately toxic
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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
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POISON!!!
Legally defined term not just anything youdont like
Any pesticide with an LD50 of 50 mg/kg orless
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
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Relative toxicity
Organisms cant differentiate betweennatural and synthetic chemicals
Synthetic does not mean toxic or poisonous Natural does not mean safe or even low risk
Chemicals must be evaluated in theirbiological context of behavior in organisms
Mode of action, not source, is the concern oftoxicologists and informed users of pesticides
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Relative toxicity
Most herbicides act on biological pathwaysnot present in humans
Those approved for use in the Region (muchmore about these later!!) have LD50s of 50mg/kg or greater they have intermediate orrelatively low toxicity
Some of the insecticides used are highlytoxic
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Relative toxicity
Some examples of pesticides and otherchemicals 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 theirrelative risk in a world of risks
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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
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Relative Toxicity:
Herbicides and Additivesmg/kg
Paraquat 95
2,4-D 3752,4-DP 532
Triclopyr 630
Tebuthiuron 644
Dicamba 757Hexazinone 1,690
Glyphosate 4,320
mg/kg
Limonene 5,000
Clopyralid >5,000Sulfometuron Met.. >5,000
Imazapyr >5,000
Diesel oil 7,380
Picloram 8,200Fosamine am.. 24,400
Kerosene 28,000
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Relative Toxicity:
Comparative informationHighly 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
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Relative Toxicity
Comparative InformationSlightly 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.
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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/kgEven water has a recognized LD50 of slightly
greater than 80,000 mg/kg
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Relative Toxicity:
The Last WordPesticides are chemicals introduced into the
environment to perform a function
The source of a chemical (synthetic vs.natural) is irrelevant when considering itstoxicity
Pesticides should be treated with care and
proper respect but so should householdcleaners, gasoline and kerosene, bleaches,paints and all other chemicals