QUESTIONS AND PROBLEMS

CHAPTER 6

1. Distinguish between acute toxicity and chronic toxicity.

Acute toxicity, which has an effect soon after exposure and chronic toxicity, which has a long
latency period.
2. Distinguish among acute local exposure, chronic local exposure, acute systemic exposure, and
chronic systemic exposure to toxicants.
Acute local exposure occurs at a specific location over a time period of a few seconds to a few
hours and may affect the exposure site, particularly the skin, eyes, or mucous membranes.
Chronic local exposure, affects the same body parts, but the time span may be long as several
years.
Acute systemic exposure is a brief exposure or exposure to a single dose and occurs with
toxicants that can enter the body, such as inhalation or ingestion, and affects organs such as the
liver that are remote from the entry site, Chronic systemic exposure differs in that the exposure
occurs over a prolonged time period.
3. List and discuss the major routes and sites of exposure, distribution, and elimination of
toxicants in the body.
Exposure:
Percutaneous route (skin)Oral route (mouth)Inhalation, Respiration, pulmonary route (lungs)4. What function is served by the stratum corneum in exposure of the body to toxic substances?
Also known as the horny layer is the major barrier to dermal absorption of toxicants.
5.Explain why the lungs are regarded as the place where substances external to the body have the
most intimate contact with body fluids. In what sense does pulmonary intake of a toxicant evade
important screening organs?
Gas exchange occurs in a vast number of alveoli in the lungs, where a tissue the thickness of
only one cell separates blood from air. The thin, fragile nature of this tissue makes the lungs
especially susceptible to absorption of toxicants and to direct damage from toxic substances.
Furthermore, the respiratory route enables toxicants entering the body to bypass organs that have
a screening effect.
7. In what sense is the gastrointestinal tract external to the body?
The gastrointestinal tract may be regarded as a tube through the body from the mouth to the anus,
the contents of which are external to the rest of the organism system.
8. How do the different regions of the gastrointestinal tract influence the uptake of toxicants,
such as weak acids, that have different acidbase behaviors?

Stomach- due to the high content of HCl and consequent low pH (about 1.0). Some
substances that are ionic at pH values near 7 and above are neutral in the stomach and
readily traverse the stomach walls.
Small Intestine- pH of the contents of the small intestine is close to neutral, so that weak
bases that are charged (HB+) in the acidic environment of the stomach are uncharged (B)
and absorbable in the intestine.
Liver serves as a screening organ for xenobiotics, subjecting them to metabolic
processes that usually reduce their toxicity, and secretes these substances or a metabolic
product of them back to the intestines.

9. What are the major components of the enterohepatic circulation system? What is the portal
circulatory system?
Enterohepatic circulation system -composed of the Gastrointestinal tract (intestine), Blood and
lymph system, liver and Bile.
Portal circulatory system- carries blood to the portal vein that goes directly to the liver.
10. Describe the nature and significance of the doseresponse curve. What is the significance of
its inflection point (midpoint)? Define dose and response.
Dose- the amount, usually per unit body mass, of a toxicant to which an organism is exposed.
Response- the effect on an organism resulting from exposure to a toxicant.
Dose-Response curve- different doses of a poison in an uniform manner are administered to a
homogeneous population of test animals and plotting the cumulative percentage of deaths as a
function of the log of the dose. An S-shaped curve is normally obtained.
The dose corresponding to the midpoint (inflection point) of such a curve is the statistical
estimate of the dose that would cause in 50% of the subjects and is designaed as LD50.
11. How do toxicity ratings relate to the potency of a toxicant?
Toxixity ratings are used to describe estimated toxicities of various substances to humans. Their
values range from one (practically nontoxic) to six (supertoxic). When there is a substancial
difference between LD50 values of two different substances, the one with the lower value is said
to be more potent.
12. Define sublethal effects, reversible effects, and margin of safety. What is an irreversible toxic
effect?
Sublethal effectsReversible effects- there is no lasting effect from the exposure
Margin of Safety- difference between the effective dose and harmful dose.
13. What are hypersensitivity and hyposensitivity? Can these phenomena be related in any
respect to the immune system?
Hypersensitivity- very sensitive to a particular poison.

Hyposensitivity- very resistant to a particular poison.

14. What is the distinction between a xenobiotic substance and an endogenous substance? What
are some examples of endogenous substances?
Xenobiotic substance- those that are foreign to a living system.
Endogenous substance- substances that occur naturally in a biologic system.
Example: various hormone, glucose (blood sugar), some vitamins, and some essential metal ions,
including Ca2+, K+, and Na+.
15. Define nonkinetic toxicology and how it relates to corrosive substances. What is kinetic
toxicology and how does it relate to systemic poisons?
Nonkinetic toxicology- deals with generalized harmful effects of chemicals that occur at an
exposure site. Applies to those poisons that are not metabolized or transported in the body or
subject to elimination processes that remove them from the body.
Kinetic toxicology- aka metabolic or pharmacologic toxicology, involves toxicants that are
transported and metabolized in the body. Systemic poisons may cross cell membranes and act on
receptors such as cell membranes, bodies in th cells, and specific enzyme systems.
16. What is a receptor? In what way may acetylcholinesterase act as a receptor? What happens
when this enzyme becomes bound to a toxic substance?
Receptor- are almost always proteinaceous materials, normally enzymes. Nonenzymes receptors
include opiate (nerve) receptors, gonads, or the uterus.
Acetylcholine is a neurotransmitter, a key substance involved with transmission of nerve
impulses in the brain, skeletal muscles, and other areas where nerve impulses occur. Some
xenobiotics, such as organophosphate compounds and carbamates inhibit acetylcholinesterase,
with the result that acetylcholine accumulates and nerves are overstimulated. Adverse effects
may occur in the central nervous system, in the autonomic nervous system, and at neuromuscular
junctions. Convulsions, paralysis, and finally death may result.
17. What is a protoxicant? What may happen to a protoxicant in the kinetic phase?
Protoxicant- precursor compound of the toxicant. In the kinetic phase a protoxicant might be
absorbed and converted to a toxic metabolic product that is transported to a location where it has
a detrimental effect.
18. What are the three major divisions of the dynamic phase? In which of these is a receptor
acted upon by a toxicant?
The three major divisions of the dynamic phase:
The toxicant reacts with a receptor or target organ in the primary reaction step
There is a biochemical response
Physiological or behavorial manifestations of the effect of the toxicant occur.
In the first phase a receptor is acted upon by a toxicant.

19. Distinguish between an active parent compound and an active metabolite in toxicology.
An active parent compound is a metabolically unmodified toxicant, while an active metabolite is
a substance modified by metabolic processes.
20. Differentiate among synergism, potentiation, and antagonism. What is an additive effect?
Synergism occurs when the total effect is greater than the sum of the effects separately,
potentiation occurs when an inactive substance enhances the action of an active one and
antagonism occurs when an active substance decreases the effect of another active one. An
additive effect is
21. Define bradycardia, tachycardia, and arrhythmia. What are some of the toxicants that may
cause each?
Bradycardia- decreased heart rate; alcohols,
Tachycardia- increaded heart rate; alcohols, Amphetamines, belladonna alkaloids, cocaine, and
tricyclic antidepressants
Arrhythmia- irregular pulse, Amphetamines, belladonna alkaloids, cocaine, and tricyclic
antidepressants
22. Distinguish between a cyanotic appearance of skin and a jaundiced appearance. Which kinds
of toxicants may cause each?
Skin with cyanotic appearance has a blue color due to oxygen deficiency in the blood while
when the skin has a jaundiced appearance it has a yellow color because of the presence of bile
pigments in the blood. Cyanotic appearance is caused by higher doses of cyanide, carbon
monozide, and nitrites. Jaundiced appearance is caused by a number of toxicants including
arsenic, arsine gas (AsH3), iron, aniline dyes, and carbon tetrachloride.
QUESTIONS AND PROBLEMS
CHAPTER 5
1. The combination of ecology and toxicology is known as ecotoxicology. Define ecotoxicology
in a way that includes environmental chemistry.
Ecotoxicology is the study of the effects of toxic substances on ecosystems.
2. Match the following pertaining to responses to toxicants at different organizational levels in
life systems:
1. Population changes
2. Physiological alterations enzyme
3. Biochemical changes
4. Ecosystem changes breathe properly
(a) Parathion from insecticide spray binds with acetylcholinesterase
(b) Animals with inhibited acetylcholinesterase enzyme cannot
(c) Numbers of animals of species most susceptible to acetylcholinesterase
enzyme inhibition decrease
(d) The decrease in animals susceptible to acetylcholinesterase
enzyme inhibition significantly affects the distribution of various
species in a defined area

3. Although lead and cadmium sulfate are both soluble, a body of water contaminated with
these \toxicants in the presence of sulfate and biodegradable organic matter shows very low
concentrations of dissolved lead and cadmium, although levels are relatively high in the
sediments of the body of water. Explain.
4. Explain why persistent organic toxicants such as DDT and PCBs are of particular concern in
ecotoxicology, even though they are not notably acutely toxic.
5. Relate chemodynamics to both ecotoxicology and environmental chemistry.
8. What are the two main pathways for the uptake of toxic substances by plants?
9. Explain how bioconcentration relates to bioaccumulation. How does the hydrophobicity model
pertain to bioconcentration? What are the conditions under which bioconcentration is most
applicable as a model?
12. Complete the following: __________________ is what happens to any substance that is
_________________by the biochemical processes in an organism and is altered by these
processes. If it proceeds all the way to simple organic species such as carbon dioxide and
ammonia, the process is called __________________.
13. Explain cometabolism as it relates to xenobiotic substances.
15. The amenability of a compound to chemical attack by microorganisms is expressed as its
_____________ and substances that strongly resist biodegradation are called
_________________.
16. Match the following pertaining to biomarkers:
1. Biomarker of exposure
2. Biomarker of effect
3. Biomarker of susceptibility
3. (a) Fish fingerlings exposed to acidic runoff from acid rain are afflicted by fungi because of
their weakened condition.
(b) A child playing on a playground contaminated by leadshows elevated levels of
carboxyhemoglobin.
(c) The blood of an individual exposed to carbon monoxide shows elevated levels of
carboxyhemoglobin.
(d) An infant fed a formula made with nitrate-contaminated water develops methemglobinemia
because of reduction of the nitrate to nitrite in the infant's stomach followed by conversion of
blood hemoglobin to methemoglobin.
17. There have been cases in which male alligators in parts of Florida have developed feminine
characteristics (perhaps roaring in a high-pitched voice), low sperm counts, and reduced size of
essential sexual organs. Suggest the class of environmental pollutant that might cause such
effects. Suggest how this effect, if it goes too far, might effect the population of alligators and the
whole ecology of the Florida Everglades that are the natural habitat of alligators.

18. Justify the statement that aquatic ecotoxicology is relatively more simple than terrestrial
ecotoxicology.
19. Explain why observation of deaths of organisms and resultant declines in populations, though
straightforward and unequivocal, are often insufficient to fully explain the effects of toxic
substances on ecosystems. Why is it important to have the capability to study sublethal effects?
20. Certain sheep that have been raised for centuries in coastal areas of Scotland exist on a diet
of seaweed that is high enough in arsenic to kill other kinds of sheep. Does this observation
illustrate pollution-induced community tolerance? Explain.