Toxicology

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 10?g 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.

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