ETM 503 Toxicology Exam

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ETM 503                                                   Exam I                                                Fall 2017

Toxicology

 

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 modules for your answer, please provide the link.

 

 

4 pts
  • 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.

  1. Why would this be a problem?
  2. How would you expect the circulating BPA in an infant to compare with an adult after the same oral dose in mg/kg?
4 pts

 

 

  1. 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 pts
  • Which of the following would be most likely to pass through a lipid bilayer by passive diffusion?
  1. a) NH4OH b) gasoline c) glucose (C6H12O6)

 

6 pts
  • 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.  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?

  1. Water has no permeability through the lipid bilayer of a membrane.
  2. Water moves through aquaporins by activated transport.

 

Explain how aquaporins transmit water molecules, but not protons?

 

 

2 pts
  • The term for the interaction of two toxins where the combined effect is greater than the sum is:
  1. Additive
  2. Synergistic
  3. Potentiation
  4. Antagonistic

 

4 pts
  • Which of the following is true about passive diffusion?
  1. a) Can move a substrate against a concentration gradient
  2. b) Does not require energy
  3. c) Is subject to saturation effects
  4. d) Can discriminate between substrates (selectivity)
5 pts

 

 

  1. 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?
3 pts

 

 

  1. Indicate the region of the respiratory system (ET, TB, or alveoli) where the following particles would most likely be deposited if breathing through the mouth.
  2. 10 µm
  3. 7 – 10 µm
  4. 1 – 5 µm

 

 

3 pts
  • What does 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) signify?
4 pts

 

 

  1. 2-butoxyethanol (butylcellosolve), C4H9-O-CH2CH2OH, is a colorless solvent used in paints, brake oils, liquid household cleaners, etc. A metabolite of 2- butoxyethanol, 2-butoxyacetic acid (BAA), C4H9-O-CH2COOH, has been identified in humans.  However, in rats, the glucouronide of 2-butoxyethanol has been identified instead of BAA.
  2. Discuss what these observations mean about how rats and humans metabolize 2-butoxyethanol.
  3. What are the implications in using rat studies of the toxicity of butylcellosolve?

 

3 pts
  • 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:
  1. Antagonistic to B
  2. A synergistic agent for B
  3. A potentiating agent for B
  4. None of the above

 

3 pts
  • By which mechanism do most toxicants cross cell membranes?
  1. Phagocytosis
  2. Membrane channels
  3. Passive diffusion
  4. Active transport

 

2 pts
  • Wet skin is ______ vulnerable to penetration by aqueous toxins than dry skin.
  1. More
  2. Less
  3. Equally

 

3 pts
  • Where does the exchange of carbon dioxide and oxygen take place in the respiratory system?
  1. Pharynx
  2. Bronchus
  3. Bronchioles
  4. Alveoli

 

3 pts
  • 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?
  1. CO2 potentiates the effect of CO
  2. CO2 is an antagonist for CO
  3. CO2 exerts a synergistic effect in combination with CO

 

3 pts
  • The specific endocytosis process by which liquids or very small particles are engulfed and transported across the membrane is known as :
  1. Phagocytosis
  2. Pinocytosis
  3. Exocytosis

 

3 pts
  • 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      “

  1. Which of these is the most lethal?
  2. How many mg of a bark scorpion bite would be lethal to a child, assuming that humans react the same as mice, if a child weighed 7.5 kg?

 

5 pts
  • 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 10 mg 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.

 

3 pts
  • In the diagram below, assuming the response is lethality:
    1. Does A or B have the higher LD50?
    2. Does A or B have the higher LOEL?
    3. Does A or B have a larger standard deviation of response?
A

 

 

B

 

3 pts
  • At pH 7.4 a weak organic acid with a pKa of 6.4 would be
  1. 10% ionized
  2. 40% ionized
  3. 60% ionized
  4. 90% ionized

 

4 pts pt s
  • Which of the following does not occur in a Phase I metabolism of a toxin?
  1. Oxidation
  2. Reduction
  3. Conjugation
  4. Hydrolysis

 

3 pts pt s
  • 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.

 

3 pts pt s
  • 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
  1. A Glucouronic acid conjugate
  2. A Sulfate conjugate
  3. A carboxylic acid
  4. An epoxide

 

6 pts pt s
  • Which of the following statements is true?
  1. Generally speaking, the ability of a substance to move across a membrane by passive diffusion by a decreasing octanol/water coefficient.
  2. Passive diffusion is subject to saturation effects.
  3. Facilitated diffusion can move substances across a membrane against a concentration gradient.
  4. The stratum corneum is rich in blood vessels.
  5. Defatting agents change the structure of cellular membranes by removing lipids.
  6. The epidermal layer of skin is easily penetrated by water.

 

5 pts
  • 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?

 

4 pts
  • Which of the following toxins would likely form a glucouronide in its initial biotransformation step? (can be more than one)
  1. a) b) CHCl3 c) CH3NH2                  d)

 

 

 

4 pts
  • Which of the following would likely react with glutathione? (can be more than one)
    1. Pb2+             c)
    2.       d)

 

 

10 pts
  1. Organomercury compounds are more dangerous to humans than inorganic forms. Is that true of arsenic as well?
  2. In general, are we more concerned about oral, inhalation, or skin exposure to arsenic?
  3. What is the oral acute MRL for inorganic arsenic?
  4. What problems are associated with using animals as models for humans for inorganic arsenic?
  5. The Mann PBPK model has how many forms of arsenic? What are the three routes of exposure considered?

 

4 pts
  • In a one box model for the elimination of a toxin
  1. The concentration of toxin in the blood is independent of the dose
  2. The half-life for elimination of the toxin is dependent on the dose
  3. The half-life for elimination of the toxin is dependent upon the route of exposure
  4. A plot of ln concentration of toxin in the blood vs time should be linear
4 pts

 

 

  1. Convert 35 ppm of methane (CH4) at 22 oC and 753 torr to mg/m3
3 pts

 

 

  1. The rate of transfer of compounds across a membrane by passive diffusion is affected by which of the following?
  2. Molecular weight
  3. Kow
  4. Molecular size
4 pts

 

 

  1. Which of the following organs plays the most minor role in biotransformation?
  2. Intestine
  3. Kidney
  4. Liver
  5. Skin

 

4 pts
  • 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.”
    1. Explain what this language means and how it could be used to arrive at a “safe” level of exposure.
    2. 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?
2 pts

 

 

  1. Blood is pumped from which part of the heart to the lungs?
  2. Left atrium
  3. Left ventricle
  4. Right atrium
  5. Right ventricle

 

2 pts
  • Which of the following amino acid residues in a protein would most likely be a target of a heavy metal such as Pb2+?
  1. Glycine
  2. Histidine
  3. Methionine
  4. Phenylalanine
5 pts

 

 

  1. Which of the following statements is true?
  2. The percent saturation of hemoglobin with O2 increases as the pH decreases.
  3. Infants are less able to reduce methemoglobin than are adults.
  4. Carbon monoxide inhibits the oxidative phosphorylation process.
  5. Disruption of the quaternary structure of proteins involves breaking peptide bonds.
  6. Cyanide competes with oxygen for binding to hemoglobin.
4 pts

 

 

  1. Explain why there is a difference in the binding curve of hemoglobin to oxygen vs myoglobin to oxygen. Why is this important?
4 pts

 

 

  1. The gas phase composition of cigar smoke is 9.7-12.7% carbon monoxide by volume. This compares to 1.9-6.3% CO in cigarette smoke (http://cancercontrol.cancer.gov/tcrb/monographs/9/m9_3.PDF).  Apparently this difference may be due to the lack of porosity in the cigar binder vs cigarette paper. What would the ratio of HbCO/HbO2 be in your blood if you were breathing air that was 12.7% CO?

 

4 pts
  • Which of the following would not be used in the treatment of poisoning by H2S?
  1. Pralidoxime
  2. Sodium nitrite
  3. Chelation therapy
  4. Sodium thiosulfate

 

4 pts
  • Which of the following inhibits cytochrome oxidase?
  1. Carbon monoxide
  2. Hydrogen sulfide
  3. Hydrogen cyanide
  4. Chlorine

 

4 pts
  • Carbon dioxide is best considered:
  1. An irritant
  2. A chronic toxin
  3. A simple asphyxiant
  4. A chemical asphyxiant
4 pts

 

 

  1. Which of the following must be in your diet?
  2. Aspartic acid
  3. Lysine
  4. Glycine
  5. Serine

 

5 pts
  • Use the HbO2 binding curve to explain your answers.
  1. Would hemoglobin be more or less likely to release oxygen in a rapidly contracting muscle cell than when the muscle cell is at rest?
  2. How would your answer change if a person was breathing 100 ppm of carbon monoxide?
  3. Why would someone suggest breathing into a paper bag to help a person who is hyperventilating?
4 pts

 

 

  1. Which of the following could cause hypoxia?
  2. Concentration of O2 in air dropping from 20.9% to 19.5%
  3. Drop in renal erythropoetic factor
  4. Breathing 1% amyl nitrite
  5. Breathing 1% helium
4 pts

 

 

  1. Pregnant women are discouraged from smoking for a number of reasons. One of them is that they are exposed to higher levels of CO when smoking.  If the presence of HbCO causes the HbO2 dissociation curve to shift to the left in pregnant women, how does that affect the fetus?

 

10 pts
  • Identify all of the following statements that are true.
  1. The LD50 of an ingested toxin may vary with the amount of food in the stomach.
  2. Particulate matter deposited in the alveoli can be cleared by the mucociliary system.
  3. Inhaled dust particles > 10 µm in diameter typically result in more toxic effects than PM5 particulate matter.
  4. Polycyclic aromatic hydrocarbons (PAHs) tend to bioaccumulate.
  5. Piperonyl butoxide (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.
  6. 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.
  7. Absorption through the skin is more likely to occur on a cold, dry day than when you are hot and sweaty.
  8. Glucose is likely to be transported through a membrane by passive diffusion.
  9. Sodium nitrite results in an increase in methemoglobin.
  10. If 2,4 D is ingested, it is less likely to be absorbed in the stomach than in the small intestine.
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