2/20/2014
Review of Concepts
to Date
Recall our very 1st slide…
• Toxicology: the study of the adverse effects of chemical
agents on living organisms; often lab animal testing
• Important terms (from EVE 486)
– Exposure pathways
– Toxicity testing
•
•
•
•
•
Dose-response curves
Acute (LD50) vs. short term vs. long term
NOAEL, LOAEL, threshold
Endpoints (carcinogenesis, reproductive toxicity…)
Difficulties (extrapolations, artifacts…)
• Goals of EVE 491/591:
– More detail on 486 topics
– Introduction to the simple biochemistry aspects
Exam #1 Topical Review
• Chapter 1
– What is toxicology?
– Toxicant vs. toxin vs. poison vs. xenobiotic
– Toxicology in antiquity
– Dose-response concept
• Chapter 2
– Atoms, elements, compounds
• Within and foreign to the body
– Mixtures, suspensions, and aerosols
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Exam #1 Topical Review (2)
• Chapter 2, continued
– Physical properties of chemicals
• pH, solubility, octanol-to-water partition coefficient,
boiling point, melting point, vapor pressure…
• Chapter 3
– Manifestations and adverse effects of toxicity
• Very minor  necrosis  death
– Factors that modify toxicity
• Age, gender, disease, etc.
Exam #1 Topical Review (3)
• Chapter 4
– Biological poisons
• Bacteria, fungi, algae, plants, animals
• Venom vs. poison
• Chapter 5
– Fate of pollutants and ecotoxicology
– DDT
• Positive and negative attributes
– Organic mercury
Exam #1 Topical Review (4)
• Chapter 5, continued
– Pollutant vs. contaminant
– Ecosystems and compartments
• Atmosphere, hydrosphere, biosphere, soils
– Toxicity in a population
• Chapter 6
– Dose-response
• The fundamental principle of toxicology
• Doses
– Administered, absorbed, internal, delivered
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Exam #1 Topical Review (5)
• Chapter 6, continued
– Effect levels and dose-response curves
• NOAEL, LOAEL, threshold, LD50
• Slope, potency
– Individual responses to a dose
• Hyporesponsive, hyperresponsive
• Body weight standardization
– Toxicity rating
– Dose of an inhaled aerosol
Exam #1 Topical Review (6)
• Chapter 7
– Toxicant entry into the body
• Barriers to absorption
– Respiratory system
» Rapid absorption and quick distribution
– Digestive system
» Liver is key
– Skin
» Vulnerable to lipophilic chemicals
– Other routes
» Intravenous, intramuscular,
– Disposition modeling
Exam #1 Topical Review (7)
• Chapters 8 and 9
– Toxicant distribution
• Compartments: plasma, interstitial, intercellular
– Toxicant storage
• Fat, bones
• Liver/kidneys – particularly efficient storage
– Toxicant elimination
• Renal, fecal, pulmonary, others
– Toxicant biotransformation (i.e., metabolism)
• Bioaccumulation, bioavailability, bioconcentration
• Key: enzymes
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2/20/2014
Lecture 1 Material
1. Which of the following would you consider not to be a xenobiotic?
a) pencillin
b) malathion
c) KCl
d) mylanta
e) all of the above
2. The best definition of a toxin is:
a) any chemical that is foreign to the body
b) any substance that can potentially produce toxicity
c) any substance that if present in the body in relatively small amounts may produce
damage
d) any poisonous substance produced by an organism
3. The best definition of a poison is:
a) any chemical that is foreign to the body
b) any substance that can potentially produce toxicity
c) any substance that if present in the body in relatively small amounts that may produce
serious injury
d) any poisonous substance produced by an organism
Lecture 2 Material
1. A _______ refers to any substance that contains more than one chemical compound
or element that has retained its individual properties
a) mixture
b) suspension
c) liquid
d) matrix
2. The specific gravity of a substance refers to
a) the ratio of the density of the material compared to the density of water
b) the weight of any substance compared to the weight of liquid oxygen
c) the density of the substance compared to the density of nitrogen
d) the weight of the substance compared to the weight of carbon
3. When the atoms of different elements combine during a chemical reaction a _______
is formed.
a) compound
b) molecule
c) mixture
d) solution
Lecture 2 Material (2)
4. A chemical with a methyl group would contain
a) CH3
b) NH2
c) KCl
d) OH
5. The regulatory agency responsible for collecting adverse events reports for drugs is the
a) FDA
b) CIA
c) OSHA
d) CDC
6. The number of chemicals in common usage in both industrial and residential settings is
approximately
a) 80,000
b) 10 million
c) 1 million
d) 1 billion
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2/20/2014
Lecture 3 Material
1. The normal process of cell death is called:
a) transcription
b) metabolic activation
c) apoptosis
d) transformation
2. Which of the following are tissue responses to chemical injury?
a) degeneration
b) circulatory and inflammatory changes
c) neoplasia
d) all of the above
e) none of the above
3. Which of the following defines sub-chronic toxicity correctly?
a) Effects of single dose/multiple dose exposures during a 24 hr period.
b) Effects of multiple dose exposures during a 14 day period.
c) Effects of multiple dose exposures during a 90 day period.
d) Effects of multiple dose exposures during more than 90 days.
Lecture 4 Material
1. Mycotoxins are produced by:
a) Viruses.
b) Fungi.
c) Bacteria.
d) Parasites.
2. Natural toxicants are:
a) Steroid hormones
b) Animal Toxins
c) Plant Toxins
d) All of the above
e) None of the above
3. The difference between toxins and venom is
a) Venom comes only from snakes
b) Venom is lethal, toxins are not
c) Venom is injected via specialized structures
d) There is no difference between them
Lecture 5 Material
1. Which of the following pollutants particularly affects fetuses and young children?
a) Sulfur dioxide
b) Ozone
c) Lead
d) Carbon monoxide
2.
a)
b)
c)
d)
Chemical pollution has been linked to
decreased fertility in animals
abnormal thyroid function in mammals
altered immune function in birds
all of the above
3. The persistence of DDT in the body is related to its lipophilic nature. True/False
4. An ecosystem can be defined as populations and communities residing in a defined
area. True/False
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2/20/2014
Lecture 5 Material (2)
5. The fate of a chemical in the air depends upon all but the following
a) dispersion
b) transport
c) reactions
d) transduction
6. Which of the following terms refers to that portion of a chemical present within the biosphere
that is potentially available for direct uptake by an organism
a) bioavailability
b) bioaccumulation
c) bioconcentration
d) bioconcentration factor
Lecture 6 Material
1. NOAEL refers to:
a) Lowest data point at which there was not an observed toxic or adverse effect
b) Highest data point at which there was not an observed toxic or adverse effect
c) Lowest data point at which there was an observed toxic or adverse effect
d) Highest data point at which there was an adverse toxic or adverse effect
2. LOAEL refers to:
a) Lowest data point at which there was not an observed toxic or adverse effect
b) Highest data point at which there was not an observed toxic or adverse effect
c) Lowest data point at which there was an observed toxic or adverse effect
d) Highest data point at which there was an adverse toxic or adverse effect
3. The amount of a xenobiotic compond encountered in the environment is:
a) Total dose
b) Administered dose
c) Exposure dose
d) Absorbed dose
Lecture 6 Material (2)
4. Which statement best describes a dose-response curve for CANCER?
a) A line that does not pass through the origin.
b) A curve with a point indicating the Lowest Observed Adverse Effect Level (LOAEL).
c) A line where there is no threshold.
d) None of the above
5. Dose standardization is best done by
a) weight
b) height
c) age
d) all of the above
6. What measure of the toxicity of a substance is measured in an acute inhalation toxicology
study?
a) LD50
b) LC50
c) LDLO
d) TDLO
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Lecture 7 Material
1. The degree of penetration of a toxicant depends on
a) Size/shape of toxicant.
b) Lipophilicity/hydrophilicity.
c) Solubility/reactivity.
d) All of the above.
2. Which exposure pathway has the fastest uptake in the human body?
a) Intravenous
b) Intramuscular
c) Subcutaneous
d) Inhalation
3. Zero order kinetics refers to:
a) Rate of elimination is directly proportional to concentration or amount of chemical
present at that time
b) Rate remains constant and independent of concentration or amount of chemical
c) Rate is dependent of concentration or amount of chemical
d) None of the above is correct
Lecture 8 Material
1.
(a)
(b)
(c)
(d)
Blood plasma water accounts for approximately what % of total body water?
5
40
10
75
2.
A high volume of distribution for a particular toxicant means that it readily distributed to
all body compartments. True/False
3. For gases that have low solubility in blood, elimination is generally less rapid than for
those that are more soluble. True/False.
4.
a)
b)
c)
d)
Which factor can affect the distribution of a toxicant in the body?
lipid solubility
blood flow to the tissue
extent of plasma protein binding
all of the above
5. Water-soluble toxicants are generally less readily eliminated by the body. True/False
Any Questions?
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2/20/2014
Case Study #2 “Kermit to Kermette?”
Refer to the handout provided (Part 2)
Questions
1.
2.
3.
A Syngenta press release quotes James Carr, head of the Texas Tech
team, as saying, “We have been unable to reproduce the lowconcentration effects of atrazine on amphibians reported elsewhere in the
scientific literature.” This statement refers to Hayes’ results (Hayes, 2002,
2003). Comment on the accuracy of this statement, and explain your
reasoning.
The Hayes study (Hayes, 2003) was conducted using water samples
collected from ponds and streams in agricultural and non-agricultural
regions of the Midwest. The study conducted by Carr’s group added
varying amounts of atrazine to de-chlorinated laboratory water. Which set
of experimental conditions, if either, would be more likely to lead to valid
experimental results? Explain your reasoning.
Comment on the significance of the Carr data, shown above, that reports
the percent of male frogs having gonadal abnormalities at a nominal
atrazine concentration of zero micrograms per liter and a nominal dose of
zero micrograms per liter.
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