Toxicology lecture 2016-17

Toxicology – EvaluatingToxicology – Evaluating
Chemical HazardsChemical Hazards

TOXICOLOGY: EVALUATINGTOXICOLOGY: EVALUATING
CHEMICAL HAZARDSCHEMICAL HAZARDS
 ToxicologyToxicology – science that examines effects– science that examines effects
of harmful chemicals on humans, wildlife andof harmful chemicals on humans, wildlife and
ecosystemsecosystems
 ToxicityToxicity – measure of how harmful a– measure of how harmful a
substance issubstance is

 Factors determining harm caused byFactors determining harm caused by
exposure to a chemical include:exposure to a chemical include:

Amount of exposure (Amount of exposure (dosedose))

Frequency of exposureFrequency of exposure

Person who is exposed (ex: adult vs. child)Person who is exposed (ex: adult vs. child)

Other chemicals exposed to (Other chemicals exposed to (multiple chemicalmultiple chemical
sensitivitysensitivity))

Effectiveness of body’s detoxification systemsEffectiveness of body’s detoxification systems

One’s genetic makeupOne’s genetic makeup

 Bell-shaped curveBell-shaped curve
showing typicalshowing typical
variations invariations in
sensitivity to asensitivity to a
toxic chemicaltoxic chemical
within awithin a
population, mostlypopulation, mostly
because of geneticbecause of genetic
variationvariation

 Other factors affecting toxicity:Other factors affecting toxicity:

SolubilitySolubility – water soluble (move through– water soluble (move through
environment) vs. fat soluble (bioaccumulate)environment) vs. fat soluble (bioaccumulate)

PersistencePersistence – resistance to breaking down– resistance to breaking down

BioaccumulationBioaccumulation – higher levels than environment– higher levels than environment

BiomagnificationBiomagnification – builds up in food web– builds up in food web

Chemical interactions – decrease or multiply effectsChemical interactions – decrease or multiply effects
• Antagonistic interaction – reduces effectsAntagonistic interaction – reduces effects
• Synergistic interaction – multiplies effectsSynergistic interaction – multiplies effects

 ResponseResponse – type or amount of health– type or amount of health
damagedamage

Acute effectAcute effect – immediate, often severe– immediate, often severe
response to single high dose exposureresponse to single high dose exposure

Chronic effectChronic effect – long-lasting response, often– long-lasting response, often
to low dose exposureto low dose exposure

 Estimating humanEstimating human
exposure andexposure and
effects is difficulteffects is difficult
because of manybecause of many
and poorlyand poorly
understoodunderstood
variables involvedvariables involved

Case Study: Protecting Children fromCase Study: Protecting Children from
Toxic ChemicalsToxic Chemicals
 Children are more susceptible to effects ofChildren are more susceptible to effects of
toxic substances because:toxic substances because:

They breathe more air, drink more water and eatThey breathe more air, drink more water and eat
more food per unit of body weight than adultsmore food per unit of body weight than adults

They are exposed to toxins when they put theirThey are exposed to toxins when they put their
fingers or other objects in their mouthsfingers or other objects in their mouths

They have less well-developedThey have less well-developed
immune systems andimmune systems and
detoxification processes thandetoxification processes than
adultsadults

Case Study: Protecting Children fromCase Study: Protecting Children from
Toxic ChemicalsToxic Chemicals
 EPA proposed regulators should assumeEPA proposed regulators should assume
children have 10X the exposure risk of adultschildren have 10X the exposure risk of adults
to cancer-causing chemicalsto cancer-causing chemicals
 Some contend regulators should assume aSome contend regulators should assume a
risk 100X that of adultsrisk 100X that of adults

 To estimate toxicity:To estimate toxicity:

Animal tests – rats, mice, primatesAnimal tests – rats, mice, primates
• Validity of extrapolating to humans?Validity of extrapolating to humans?
• Synergistic effects?Synergistic effects?

Mathematical models – to estimate effectsMathematical models – to estimate effects

Case reportsCase reports – examples of human exposure– examples of human exposure

Toxicological studies on wildlifeToxicological studies on wildlife

Epidemiological studiesEpidemiological studies (experimental vs.(experimental vs.
control groups)control groups)

 Animal tests useAnimal tests use median lethal dose (LD50)median lethal dose (LD50) ––
dose at which 50% of animals die (mg/kg)dose at which 50% of animals die (mg/kg)
dose-response curvedose-response curve::
threshold level

 Two types of dose-response curves:Two types of dose-response curves:

Nonthreshold dose-response modelNonthreshold dose-response model – any dosage of a– any dosage of a
toxic chemical causes harm that increases with thetoxic chemical causes harm that increases with the
dosagedosage

Threshold dose-response modelThreshold dose-response model – must reach certain– must reach certain
level of exposure before harmful effectslevel of exposure before harmful effects

Are Trace Levels of Toxic ChemicalAre Trace Levels of Toxic Chemical
Harmful?Harmful?
 Insufficient data for most chemicalsInsufficient data for most chemicals
 We are all exposed to toxic chemicalsWe are all exposed to toxic chemicals

Trace amountsTrace amounts
 Difference between increasing dangers andDifference between increasing dangers and
better testingbetter testing

 Under existing laws, most chemicals areUnder existing laws, most chemicals are
consideredconsidered innocent until proven guiltyinnocent until proven guilty

We do not know if we should be concernedWe do not know if we should be concerned

EEstimating their toxicity is difficult, uncertain andstimating their toxicity is difficult, uncertain and
expensiveexpensive

Only 2% of 100,000 chemical have beenOnly 2% of 100,000 chemical have been
adequately testedadequately tested

Federal and state governments do not regulateFederal and state governments do not regulate
about 99.5% of the commercially used chemicalsabout 99.5% of the commercially used chemicals
in the U.S.in the U.S.

 Some say preliminary – not conclusive –Some say preliminary – not conclusive –
evidence that a chemical causes significantevidence that a chemical causes significant
harm should spur preventive actionharm should spur preventive action
((precautionary principleprecautionary principle))

Assumed harmful until shown not to beAssumed harmful until shown not to be

Not on market until shown to be safeNot on market until shown to be safe
 Manufacturers say wide-spread applicationManufacturers say wide-spread application
of precautionary principle makes it tooof precautionary principle makes it too
expensive to introduce new chemicals andexpensive to introduce new chemicals and
technologiestechnologies

Toxicology lecture 2016-17

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Toxicology lecture 2016-17