+1 862 207 3288 Please make sure that your answers can be read in black and white printing.
Multiple choice questions may have more than one correct answer. Indicate all correct answers.
A number of the multiple choice questions are taken from CIH exams (Certified Industrial Hygienist).
If you use a reference other than my notes for your answer, please provide the link.
1. BPA, bis(4-hydroxyphenyl) dimethylmethane or bisphenol A, has been in the news lately. Its structure is shown below.
It is used widely in the manufacture of plastics and now is ubiquitous in humans. It has been found in 93% of urine samples in one
study; other studies have found it in breast milk, blood and other tissue samples. Fetuses and newborns have little UDP glucuronidase
compared to adults.
a) Why would this be a problem?
b) How would you expect the circulating BPA in an infant to compare with an adult after the same oral dose in mg/kg?
2. Suppose you had data on the lethality of Aflotoxin B1 as follows:
Dose ppb Deaths
0.5 0/18
1 1/22
5 2/22
15 4/21
50 20/25
100 28/28
150 28/28
Graph this data in a log dose vs response relationship and estimate the LD50 for Aflotoxin B1.
3. Which of the following would be most likely to pass through a lipid bilayer by passive diffusion?
a)NH4+ b) C6H6 c) Pb2+ d) glucose (C6H12O6)
4. Please look at the Nobel Prize lecture by Peter Agre found at http://www.nobelprize.org/mediaplayer/index.php?id=547 and answer
the following questions. You need only look at the first 20 minutes or so of the lecture which focuses on membranes. Dr. Agre also
references some topics we’ll be covering in the future, including protein structures and kidney functions, so I want you to get a taste
of how he was able to piece together the structure and function of aquaporins.
Which of the following statements is true?
a) Water has no permeability through the lipid bilayer of a membrane.
b) Water moves through aquaporins by activated transport.
Explain how aquaporins transmit water molecules, but not protons?
5. A reference dose (RfD) applies to
a) Non-carcinogens
b) Carcinogens
c) Mutagens
d) Teratogens
6. The term for the interaction of two toxins where the combined effect is greater than the sum is:
a) Additive
b) Synergistic
c) Potentiation
d) Antagonistic
7. In 1976 an industrial accident occurred involving the town of Seveso in Northern Italy. Name the toxin that was released in the
accident and the herbicide that was being manufactured when the accident happened? Name two target organs affected by exposure to the
toxin released at Seveso and the pathology produced in these organs?
8. Why can you have a zero order rate constant for carrier mediated transport across a membrane (meaning the rate of transport
does not increase as the concentration of the material being transported increases)?
9. A worker is exposed to chemical A and no effect is produced. Then the worker is exposed to chemical A and chemical B. A
marked effect, much greater than the effect of B alone, is seen. Chemical A is:
a) Antagonistic to B
b) A synergistic agent for B
c) A potentiating agent for B
d) None of the above
10. Antibuse (disulfiram) is used to treat alcoholism by blocking the activity of acetaldehyde dehydrogenase according to the
following. Acetaldehyde is more toxic than ethanol and is responsible for hangover effects. So taking antibuse makes you very sick if
you drink alcohol. Is the action of acetaldehyde dehydrogenase a Phase I or a Phase II reaction?
Alcohol dehydrogenase Acetaldehyde dehydrogenase
CH3CH2OH CH3CHO CH3COO-
Ethanol Acetaldehyde Acetate
11. By which mechanism do most toxicants cross cell membranes?
a) Phagocytosis
b) Membrane channels
c) Passive diffusion
d) Active transport
12. Inhaled dust particles > 10 µm in diameter:
a) Often penetrate to the alveoli
b) Are filtered out in the ET region
c) Are filtered out in the TB region
d) Are typically more toxic than PM2.5
13. Wet skin is ______ vulnerable to penetration by aqueous toxins than dry skin.
a) More
b) Less
c) Equally
14. Where does the exchange of carbon dioxide and oxygen take place in the body?
a) Pharynx
b) Bronchus
c) Bronchioles
d) Alveoli
15. The LC50 for carbon monoxide alone is 6600 ppm. For a mixture of carbon monoxide and 5% carbon dioxide, the LC50 for CO drops
to 3900 ppm. 5% carbon dioxide by itself is not lethal. Which of the following statements is appropriate based on this data?
a) CO2 potentiates the effect of CO
b) CO2 is an antagonist for CO
c) CO2 exerts a synergistic effect in combination with CO
16. The specific endocytosis process by which liquids or very small particles are engulfed and transported across the membrane is
known as :
a) Phagocytosis
b) Pinocytosis
c) Exocytosis
17. The LD50 for a mouse subjected to the following toxins is as follows:
Bark scorpion 1.12 mg/kg
Black widow spider 0.90 “
Copperhead snake 10.5 “
Mohave rattler 0.23 “
Western diamondback 4.2 “
a) Which of these is the most lethal?
b) How many mg of a bark scorpion bite would belethal to a child, assuming that humans react the same as mice, if a child weighed
7.5 kg?
18. Assume toluene has an acute NOAEL of 5 mg/kg/day. You are a mother camping with your child for a day and your child begins
complaining of a stomach ache. Later you learn that the campground has been contaminated with a gasoline spill and that the soil
contains 300 mg toluene/kg of soil, the ground water used for drinking contains 10g toluene/L, and in the fish that you caught
contains 5 mg toluene/kg. (You might not want to go back to this campground!)
Assume the following:
Body Water Fish Soil
Weight consumed consumed consumed
Child 20 kg 1 L 200 g 200 mg
Is it likely that the stomach ache is due to ingestion of toluene? Explain and show your calculations.
19. In the diagram below, assuming the response is lethality:
a) Does A or B have the higher LD50?
b) Does A or B have the higher LOEL?
c) Does A or B have a larger standard deviation of response?
20. At pH 7.4 a weak organic acid with a pKa of 6.4 would be
a) 10% ionized
b) 40% ionized
c) 60% ionized
d) 90% ionized
21. Which of the following does not occur in a Phase I metabolism of a toxin?
a) Oxidation
b) Reduction
c) Conjugation
d) Hydrolysis
22. Urinary excretion of ClHC=CH-CH2S-CH2-CH(COOH)
|
NH-CCH3
||
O
has been correlated to 8 hr time weighted average exposure to 1,3-dichloropropene (DCP, a soil fumigant used in agriculture, ClHC=CH-
CH2Cl). Explain what this tells us about how DCP is metabolized in the body.
23. Benzene is oxidized to phenol by cytochrome P-450 monooxygenase. The intermediate compound in this process that causes the
most concern because of its toxicity is
a) A Glucouronic acid conjugate
b) A Sulfate conjugate
c) A carboxylic acid
d) An epoxide
24. Which of the following statements is true?
a) Generally speaking, the ability of a substance to move across a membrane by passive diffusion is enhanced by decreasing size
and by an increasing octanol/water coefficient.
b) Passive diffusion is subject to saturation effects.
c) Facilitated diffusion can move substances across a membrane against a concentration gradient.
d) The stratum corneum is rich in blood vessels.
e) Defatting agents change the structure of cellular membranes by removing lipids.
f) The epidermal layer of skin is easily penetrated by water.
25. Aluminum in blood plasma was shown to undergo a first order elimination reaction with a half-life of 160 days. If the initial
concentration was 6.5 µg/L, how long will it take for the concentration to drop to 2.5 µg/L?
26. Which of the following toxins would likely form a glucouronide in its initial biotransformation step? (can be more than one)
a) b) CHCl3 c) CH3NH2 d)
27. Which of the following would likely react with glutathione? (can be more than one)
a) Pb2+ c)
b) d)
28. Using the ASTDR Toxicological Profile of Arsenic (http://www.atsdr.cdc.gov/toxprofiles/tp2.pdf) answer the following questions.
Reference the page numbers of the document where you found each of your answers.
a) Organomercury compounds are more dangerous to humans than inorganic forms. Is that true of arsenic as well?
b) In general, are we more concerned about oral, inhalation, or skin exposure to arsenic?
c) What is the oral acute MRL for inorganic arsenic?
d) What problems are associated with using animals as models for humans for inorganic arsenic?
e) The Mann PBPK model has how many forms of arsenic? What are the three routes of exposure considered?
29. In a one box model for the elimination of a toxin
a. The concentration of toxin in the blood is independent of the dose
b. The half-life for elimination of the toxin is dependent on the dose
c. The half-life for elimination of the toxin is dependent upon the route of exposure
d. A plot of ln concentration of toxin in the blood vs time should be linear
30. Convert 35 ppm of methane (CH4) at 22oC and 753torr to mg/m3
31. Which of the following organs plays the most minor role in biotransformation?
a) Intestine
b) Kidney
c) Liver
d) Skin
32. Over 10 billion pounds of styrene are produced each year in the U.S. The following is a quote from a toxicology text about a
drinking water standard for styrene: “NAS (National Academy of Sciences) calculated a suggested no-adverse-effect level in drinking
water (for humans) of 0.9 mg/L based on a rat NOAEL from a 185 day study and using an uncertainty factor of 1000.”
a) Explain what this language means and how it could be used to arrive at a “safe” level of exposure.
b) If an average adult weighs 75 kg and drinks 2 L per day, and a rat weighs 0.5 kg, what would the NOAEL daily dose in mg have
been for a rat?
33. Identify all of the following statements that are true.
a) The LD50 of an ingested toxin may vary with the amount of food in the stomach.
b) Particulate matter deposited in the alveoli can be cleared by the mucociliary system.
c) Piperonylbutoxide (a toxic substance) added to pyrethrum insecticide results in a pyrethrum formulation having about 100 times
the toxicity of pyrethrum alone. This is an example of synergism.
d) Exposure to methyl parathion after exposure to malathion increases the observed effects by approximately the amount that
exposure to methyl parathion alone would have. This is an example of an additive effect.
e) Absorption through the skin is more likely to occur on a cold, dry day than when you are hot and sweaty.
f) Glucose is likely to be transported through a membrane by passive diffusion.
g) If 2,4 D is ingested, it is less likely to be absorbed in the stomach than in the small intestine.
ETM 503 Sample Questions Spring 2016
Toxicology Weeks 1 – 4
1. The amount of a chemical that kills 50% of the organisms exposed to it in air is the
a) LD50
b) TD50
c) ED50
d) LC50
LC refers to lethal concentration which is used for air concentrations that are inhaled. LD refers to lethal dose which is used for
other routes of exposure.
2. Isopropanol is not toxic to the liver, whereas carbon tetrachloride does cause liver damage. When exposed to a mixture of
isopropanol and carbon tetrachloride the effect is much greater than to the same dose of carbon tetrachloride alone. On the other
hand, ethanol is toxic to the liver and the combination of ethanol and carbon tetrachloride is more toxic than the sum of the toxicity
of each. Which of the following is true?
a) Isopropanol is antagonistic to carbon tetrachloride, whereas ethanol is synergistic.
b) Isopropanol potentiates carbon tetrachloride, whereas ethanol is synergistic.
c) Isopropanol and ethanol have an additive effect with carbon tetrachloride.
d) Isopropanol potentiates carbon tetrachloride, whereas ethanol has an additive effect.
3. Convert 50 mg/m3 of mercury vapor to ppm (assuming 20oC and 740 torr).
Density of a gas is g/L = P(MW)/RT
Under these conditions of P and T, the density of Hg vapor is:
g/L = (740 torr x 1 atm/760 torr)(200.59 g/mole) = 8.12 g/L
(0.0821 Latm/moleK)(293 K)
1 ppm = 1 L Hg = 1 L Hg = 0.001 L Hg/m3 air = 0.00812 g/m3
106 L of air 1000 m3 of air
= 8.12 mg Hg/m3 of air
50 mg/m3 = 6.2 ppm
8.12 mg/m3/ppm
4. Distinguish between the NOEL and the LOEL.
NOEL is No Observable Effect Level –the highest dose at which no effect is observed.
LOEL is Lowest Observable Effect Level – the lowest dose at which an effect is observed.
NOEL should be less than LOEL
5. If the NOAEL for styrene in the drinking water for a rat is 12.0 mg/L/day, what would a safe human dose for a human be in mg
styrene/L water? Assume a human weighs 75 kg and a rat weighs 0.5 kg. Assume an uncertainty factor of 1000. Assume a rat drinks 50
ml of water per day and a human drinks 2 L of water per day.
12.0 mg styrene/L x 0.05 L/day = 0.6 mg styrene/day = NOAEL for a rat
0.6 mg/day = 1.2 mg/kg/day for a rat
0.5 kg
1.2 mg/kg/day x 75 kg = 0.09 mg styrene/day for a human for NOAEL
1000
If a human drinks 2 L/day, then the water could contain no more than
0.09 mg/day = C (mg/L) (2 L/day)
C = 0.045 mg/L in the water
6. Identify all of the following statements that are true (more than one can be true for this question).
a) LD50 does not depend upon route of exposure.
b) An ingested toxin that passes through the GI tract and is excreted is not considered to be an absorbed dose.
c) Antibuse taken alone typically has no effect on an individual, but taken with alcohol causes a severe response after only one
drink. This is an example of synergism.
This would be potentiation.
d) The toxicity of mercury is reduced by administration of the chelate mercaprol. This is an example of antagonism.
e) Acute poisoning refers to repeated low doses of toxin over a period of years.
7. Would you be more concerned about acute or chronic effects from the following? Explain.
a) a spill of hydrochloric acid on your hand acute
b) breathing air containing asbestos fibers chronic
c) ingestion of water containing 5 ppb benzene chronic
8. Which material is more easily absorbed through the skin and into bloodstream? Why?
a) ethylene glycol (antifreeze) [CH2CH2]
| |
OH OH
b) trichloroethylene (TCE) Cl2C=CHCl more lipid soluble
9. After long term, low level exposure to PCBs [polychlorinated biphenyls], would you expect its concentration to be higher in
blood or fatty tissue? Explain.
Fatty tissue because PCBs are hydrophobic (don’t dissolve in water).
10. Consider the following dose-response curve.
a) Which toxicant (A or B) is “safer”? Explain.
b) What difficulties would be encountered with toxicant B?
A B
Resp
50% ———————
Dose
From an LD50 standpoint, A has a lower value and is thus “more toxic” but the dose-response curve for B is much flatter, meaning that
some individuals would respond to B before A. The LOEL for B would be much lower than for A.
11. Discuss the factors that could affect individual response to a dose of a toxin.
Age, sex, and nutritional or health status could distinguish between individuals in the same population. Different species may have a
different metabolic mechanism for the toxin.
12. Aniline, is considered a carcinogen, yet is widely encountered in the chemical and dye industry. If aniline is ingested,
where would it be more likely to be absorbed: the stomach or small intestine? Why?
Aniline is a weak base. In an acid environment, like the stomach, it is protonated and carries a positive charge. This makes it
difficult to penetrate a membrane. It would be more likely to be absorbed in the intestine.
13. Distinguish between passive diffusion and carrier mediated transport.
Both are diffusion driven processes (from high concentration to low) and neither requires energy. But passive diffusion depends upon
lipid solubility (Kow) and size. Carrier mediated transport has proteins designed to transport specific molecules across the boundary
that might not otherwise penetrate because of its polarity. Rate limited by number of proteins.
14. Suppose that you are an emergency responder to a fire involving magnesium metal (magnesium oxide smoke ranges in size from 0.01
to 0.5 m). How concerned should you be about breathing air that might contain the by products of this fire? Explain.
This PM is small enough that it can enter the alveolar region of the lung, although it is smaller than the particle size with highest
deposition rate. It cannot be trapped with just a “dust” mask but requires a fitted respirator. It could be very dangerous.
(Something like 80% of the emergency responders to the World Trade Center on 9/11 are now reporting serious respiratory diseases).
15. Nicotine is metabolized by a flavin containing monooxygenase (FMO) according to the following reaction. Is this a Phase I or a
Phase II reaction?
Phase I
16. The factor which is primarily responsible for dust gaining entrance to the alveolar region of the lung is:
a) Composition of the dust
b) Concentration of absorbed species on the surface
c) Particle size
d) Condition of the mucociliary system
17. In a one box model for the elimination of a toxin
a) The concentration of toxin in the blood is independent of the dose
b) The half-life for elimination of the toxin is dependent on the dose
c) The half-life for elimination of the toxin is dependent upon the route of exposure
d) A plot of ln concentration of toxin in the blood vs time should be linear
A one box model assumes first order kinetics. The half-life is independent of concentration for a first order reaction.
18. Using the ASTDR Toxicological Profile of Mercury reference (http://www.atsdr.cdc.gov/toxprofiles/tp46.html), answer the
following questions. Reference the page numbers of the document where you found each of your answers.
a) What are three common sources of mercury in the environment that could potentially impact humans?
b) Does the body absorb elemental mercury as well from ingestion as from inhalation?
c) What are three target organs in the body resulting from mercury exposure?
d) What would be considered a lethal exposure for humans to elemental mercury vapor?
e) Is there any lower level of mercury vapor that is considered “safe” for humans to breath?
f) In the Farris PBPK model, what is the product of the biotransformation of methyl mercury? What were the four target tissues?
How was the methyl mercury introduced?
You might have different page references, but here are some that will work.
a) Metallic or elemental mercury is found in many products such as thermometers, barometers, and batteries. Organic mercury
compounds are found in fish or shellfish. Inorganic mercury salts are found in skin lightening creams and bactericides or fungicides.
(p. 3)
b) About 80% of inhaled elemental mercury vapor is absorbed by the body, but less than 0.01% of ingested mercury is absorbed. (p.
11).
c) The central nervous system, brain, and kidneys as well as lining of mouth and lungs have been identified (p. 12-13).
d) Exposure to rats of 27 mg/m3 for 2 hours resulted in premature death of 20 out of 32 rats. 1 out of 2 rabbits died after
exposure to 28.8 mg/m3 for 30 hours. Thus, this level is potentially a fatal dose. (p. 34)
e) OSHA PEL for mercury vapor is 0.05 mg/m3 (p. 27)
f) Discussion of Farris model begins on p. 194. Methyl mercury was converted to inorganic mercuric ion. Four of the target
organs were blood, liver, kidney, and GI tract. Methyl mercury was introduced in a single oral dose.
19. Benzene is biotransformed in the body to phenyl sulfate as shown below
Which of the following statements is true?
a) Both steps are examples of Phase I reactions
b) Both steps are examples of Phase II reactions
c) Step I is a Phase I and step II is a Phase II reaction
d) Step I is a Phase II and step II is a Phase I reaction
15. Which of the following toxins would likely react with glutathione?
g) CH3CH2CH2CH3 b) c) d) CH3CH2COOH
Glutathione is a nucleophile. Means it reacts with carbon atoms that carry a positive charge (such as alkyl halides) or metal ions.
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