Take-home Quiz for PG 661.
Fall, 1997

Answer any 5 questions on your own. Unless stated otherwise I anticipate that each answer should require about a page. Turn in your work, typed, on Oct 13, 1997.

1 Identify a compound that causes the following problems, state what the likely functional consequences would be. Also state where such an effect would likely appear on a functional observational battery as described in your readings. If you think that it won't appear then say so.

a. myelin degeneration

b. destruction of the hippocampus

c. degeneration of dopamine receptors

d. axonal degeneration in the peripheral nervous system

a. myelin degeneration

b. damage to hippocampus

c. degeneration of dopamine receptors

d. axonal degeneration in the peripheral nervous system

2. Define the following terms and illustrate them on properly labeled graphs:

a. ED 50

b. ED 01

c. LD 50

d. Tolerance

e. Sensitivity

f. Margin of Safety

3. a. 1,1,1 Trichloroethane, and trichloroethylene are organic solvents whose half-life of elimination has been estimated at 6 hours. Draw an accurately labeled graph showing the theoretical curve showing the elimination of this compound. Let the concentration at time t=0 be 100% (i.e., normalize to peak concentration) and show only the elimination curve.

b. Do the same for a compound, say a metal, whose half-life of elimination is 365 days.

c. How long does it take for 95% of each compound to be eliminated? Discuss the implications for the possibility of accumulation for each compound if exposure occurs once/week.

4. Summarize in 600 words or so, and up to 2 figures, how Cox et al. validated hair as a biomarker of mercury exposure. Do this in such a way that the general approach could be used as a model for developing a biomarker of exposure. For example, identify the key general elements in developing such a biomarker. Identify any gaps in this validation that should be addressed.

5. Some pesticides inhibit the action of acetylcholinesterase. Describe the autonomic signs that you would expect to see from this action. Describe a pharmacological intervention that could be used to treat such poisoning and state why this would work.

6. Define and discuss the concept of the discriminative stimulus. Include in your discussion some consideration of exteroceptive and interoceptive stimulus control, and whether and how these differ conceptually and methodologically. Be sure to describe the role of reinforcers in establishing a discriminative stimulus.

7. Pretend that you are in a position to start a new department to study neurotoxic chemicals for a large corporation, say, Dowpont-Kodiak, inc. You have adequate resources to support five Ph.D. level people and support staff. In two or three pages sketch a plan of action. Include a brief long-range plan describing how you would decide what initial approach you would take, what you hope to be doing in five years, and what realistic accomplishments you would like to achieve at the end of five years

Item pool.

1. This question pertains to an over-the-counter treatment for head-lice uses a pyrethroid insecticide. Feel free to use illustrations (drawn by you) to answer this question.

a. Give the name of the compound.

b. Describe its likely action on ion channels on the neural membrane.

c. Describe what this will do to the action potential.

d. What effect would this have at the synapse?

e. In a paragraph or two, state what considerations you would use in determining the risk to children associated with using this material.

2. Diagram a neuron and show the relevant structures.

3. Describe the importance of lipid solubility in understanding whether a compound is neurotoxic.

4. Identify a compound that causes the following problems, state what the likely functional consequences would be and state whether such an effect would likely appear on a functional observational battery as described in your readings.

a. myelin degeneration

b. damage to hippocampus

c. degeneration of dopamine receptors

d. axonal degeneration in the peripheral nervous system

5. Define the following terms and illustrate them on properly labeled graphs:

g. ED 50

h. ED 01

i. LD 50

j. Tolerance

k. Sensitivity

l. Margin of Safety

6. a. 1,1,1 Trichloroethane, and trichloroethylene are organic solvents whose half-life of elimination has been estimated at 6 hours. Draw an accurately labeled graph showing the theoretical curve showing the elimination of this compound. Let the concentration at time=0 be 100% (i.e., normalize to peak concentration) and show only the elimination curve.

b. Do the same for a compound, say a metal, whose half-life of elimination is 365 days.

c. How long does it take for 95% of each compound to be eliminated? Discuss the implications for the possibility of accumulation for each compound if exposure is weekly.

7. a. Summarize in 600 words, or so, and up to 2 figures, how Cox et al. validated hair as a biomarker of mercury exposure. Do this in such a way that the general approach could be used as a model for developing a biomarker of exposure. For example, identify the key general elements in developing such a biomarker. Identify any gaps in this validation that should be addressed.

8. Some pesticides inhibit the action of acetylcholine esterase. Describe the autonomic signs that you would expect to see from this action. Describe a pharmacological intervention that could be used to treat such poisoning and state why this would work.

9. Define and discuss the concept of reinforcement as defined in laboratory procedures. Keep your discussion focused on what is done and what happens, i.e., keep it operational. Describe how this concept has been used to evaluate learning in a laboratory.

10. Define and discuss the concept of the discriminative stimulus. Include in your discussion some consideration of exteroceptive and, interoceptive stimulus control, and whether and how these differ conceptually and methodologically.

11. Pretend that you are in a position to start a new department to study neurotoxic chemicals for a large corporation, say, Dowpont-Kodiak, inc. You have adequate resources to support five Ph.D. level people and support staff. In two or three pages sketch a plan of action. Include a brief long-range plan describing how you would decide what initial approach you would take, what you hope to be doing in five years, and what realistic accomplishments you would like to achieve at the end of five years.
 
 

1. Discuss the difficulties associated with identifying an ED01.

2. Name and briefly describe the types of neurons.

3. Name and briefly describe the different types of glial cells

4. Briefly describe the structure of the neuron.

5. Diagram a neuron

6. Describe the critical components of the action potential. Describe the roll of ion channels.

7. Describe the resting potential. What is its value? What does that mean?

8. What toxicants alter the function of ion channels, and what do they do? Which of these are toxins?

9. Describe the different stages of neurotransmission.

10. Memorize Table 2-2

11. Describe the blood-brain barrier. Be sure to describe gaps in it.

12. Describe the different ways in which compounds can penetrate (or fail to penetrate) the blood brain barrier.

13. Discuss "lipid-solubility." Define it and describe its roll in neurotoxicology.

14. When does neural development begin? When does it end?

15. What are some of the ways in which chemicals can interfere with neural development? How might you determine whether these result in functional consequences?

16. What are "trophic interactions?"

17. What compounds cause myelin degeneration? damage to hippocampus? degeneration of dopamine receptors? axonal degeneration in the PNS? What might be the functional consequences of such damage?

18. Describe anterograde and retrograde axonal transport. How fast does it take place? The longest neural process is about 1 meter long (in the human). How long will it take for these transport to take place in such a neuron.

19. Describe the actions of organophosphate pesticides. LSD. Hydrogen peroxide.

20. Describe the toxic sequelae associate with pyrethroid exposure. Name some pyrethroids. Don't memorize the structures.

21. Describe the toxic sequelae associate with n-hexane. Memorize the structure of n-hexane and 2,5 hexanedione.

22. Describe the toxic sequelae associated with MPTP. How many steps are involved in the conversion to MPP+? What prevents it.

23. What are the three general classes of events that biomarkers should mark?

24. Name and describe representative biomarkers for each of the three classes.

25. Define the following terms and illustrate them on properly labeled graphs:

a. ED 50

b. ED 01

c. LD 50

d. Tolerance

e. Sensitivity

f. Margin of Safety

26. Discuss the difficulties associated with identifying an ED01.

27. Describe the difference between "organic" and "elemental" mercury. Describe the different sources of these two species of mercury, their kinetics in the nervous system, and their transport across physiological barriers.

28. Discuss the rationale for using behavioral screens.

29. Discuss the "tiered" strategy for screening. What are their strengths? Weaknesses?

30. Describe the desirable characteristics of a behavioral screen. Be sure to mention reliability, sensitivity, the types of errors and their consequences.

31. Describe the role of Structure-Activity relationships in behavioral testing.

32. Discuss the merits and deficiencies of "in vivo" strategies for neurotoxicity testing. What are some of the strategies?

33. Describe the Functional Observational Battery. Why was it invented? What are its merits and deficiencies?

 

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