Biology 137 Introduction to Toxicology Midterm Exam 1 Part I. Multiple choice. Two points each. 1.

Name Fall Semester 2001

Toxicology is the study of A. prevalence of disease and death in a population B. adverse effects of chemicals on living organisms C. the appearance of symptoms produced by infectious agents D. word origins E. none of the above In the human body, toxicological processes ultimately take place at which level? A. cell B. tissue C. organ D. organ system E. the whole organism Which type of toxicologist is concerned with the use of toxicants by the public and in the workplace? A. descriptive toxicologist B. mechanistic toxicologist C. regulatory toxicologist Which is the best definition of the term toxicant? A. a chemical that causes no adverse effects B. a substance produced as a result of human activities C. a branch of toxicology D. an agent that neutralizes the effects of a poison E. a substance that is naturally produced The statement, "All substances are poisons; there is none which is not a poison. Only the dose determines that a thing is not a poison" , is attributed to which of the following? A. Hippocrates B. Theophrastus C. Mithridates D. Paracelsus E. Catherine DiMedici Toxicity is recognized when on the administration of a chemical an observable and quantifiable is identified. A. mutagen B. waste product C. dose D. end-effect or response E. safety factor A substance that is being tested for toxicity is injected intramuscularly mixed with peanut oil. The term vehicle in this case refers to: A. the syringe used B. the needle type used C. the manner in which the substance was transported to the lab D. the peanut oil E. none of the above

2. 3.

4.

5.

6.

7.

For the following (8-12) select the most appropriate answer in column B for each item in column A below. Column A 8. 9. 10. 11. 12. 13. acute toxicity systemic toxicity local toxicity delayed toxicity Column B A. Symptoms restricted to the site of initial exposure B. Toxicity occurring within less that 24 hours C. toxic effects occur within the body, at sites far removed from exposure site D. dead and lost cells replaced by cell division

reversible toxic effect E. the appearance of cancerous tumors 25-30 years after exposure to a toxin. The sigmoid (s) dose response curve for a toxicant indicates a threshold dose below which no effects are observed. A threshold occurs because of A. saturation of biotransformation pathways. B. saturation of protein binding sites. C. saturation of receptor sites. D. depletion of cofactors. E. All of the above are possible reasons. 1

14.

In the figure above, toxin A is than toxin B and toxin C is than toxin D. A. less potent, less efficacious B. more potent, more efficacious C. less potent, more efficacious D. more potent, less efficacious The sigmoid (s) dose response curve is usually converted into a probit probability presentation. Each probit unit of the transformed data represents A. 50% of the population B. 99.7% of the population. C. one standard deviation. D. two standard deviations. E. the LD50 value obtained from the plot. A weak organic acid with a pKa of 5.5 would be expected to be A. more ionized at low pH B. more ionized at high pH C. non-ionized at low pH D. non-ionized at high pH E. both (B) and (C) are true A contaminant in the local drinking water is at a concentration of 0.2 mg/ml. What will be the average daily dose (mg/kg) of the contaminant for a mouse. Mouse water consumption per day is 5 ml and the mouse weight is 30 grams. A. 6.66 mg/kg B. 33.33 mg/kg C. 0.033 mg/mouse D. 6.55 mg/ml E. 0.66 mg Column A Column B A. equal to the sum of effects of each agent given alone. B. combined effect of two chemicals is greater than the sum of effects of each. C. one substance is not toxic but when added to another toxic chemical it makes that chemical more toxic D. when two chemicals interfere with each other's actions

15.

16.

17.

For the following (18-21) match the item in column B with the item in column A. 18. 19. 20. Additive effects Potentiation effects Antagonistic effects

21.

Synergistic effects

22.

The "first pass effect" refers to A. rejection on a first date B. a toxicant passing through the circulation for one cycle C. elimination of a toxicant before it is distributed by the blood stream D. successfully completing this course the first time E. none of the above For a gas with a high solubility in plasma, absorption in the lungs depends more on respiration rate than on pulmonary blood flow. A. True B. False Chemicals are more readily absorbed through the skin or GI tract if they are A. polar compounds B. ionic compounds C. lipid soluble D. non-ionic, neutral compounds E. both (C) and (D) Metalothionein is a special protein that binds metals in the A. liver B. GI tract C. type I pneumocytes D. nasal passages With respect to excretion of toxic substances which of the following is the correct order of importance of the three major routes? A. fecal>lung>kidney B. lung>fecal>kidney C. fecal>kidney>lung D. kidney>fecal>lung Which of the following processes or interactions would interfere with the delivery of the ultimate toxicant to its target site (intracellular molecule) where it produces the toxic effect? A. increased porosity of capillaries B. reabsorption C. specialized membrane transporters D. activation of the toxicant (toxication) E. excretion Excretion of weak organic bases by the kidney is favored by and reabsorption of weak organic acids by the kidney tubule epithelium is favored by in the forming urine. A. high pH, high pH B. low pH, low pH C. high pH, low pH D. low pH, high pH Which of the following would be considered a detoxication biotransformation process? A. formation of electrophiles B. formation of free radicals C. conjugation with glucuronic acid D. formation of redox-active reactants E. Both (A) and (B) Dysregulation of gene expression can result from by the toxicant. A. disruption of DNA transcription B. interference with promoter regions of genes C. interference with phosphorylation networks involved in signal transduction D. interference with signal production E. all of the above. Class B substances that are excreted by the liver have a bile to plasma concentration ratio that is greater than 1. These substances are probably A. excreted by passive processes if they are lipophilic. B. actively transported by the hepatocytes. C. reabsorbed in the bile ducts. D. not excreted rapidly. Which of the following would enhance the absorption of a toxicant through the various skin layers. A. hydrophilicity B. lipophilicity C. active transport mechanisms D. hydration of the skin E. Both (B) and (D) Toxins get across the placenta to the developing fetus A. by active transport processes B. by simple diffusion C. by paracellular transport D. through fenestrated capillaries E. with difficulty because the placenta acts as a barrier much like the blood brain barrier. 3

23.

24.

25. 26.

27.

28.

29.

30.

31.

32.

33.

34

The most important contributing source for excretion of toxicants via the fecal route is A. intestinal secretion. B. exfoliation of intestinal cells. C. biliary excretion. D. pancreatic excretion. E. none of the above. Disposition refers to the of toxic substances. A. absorption B. distribution C. biotransformation D. excretion processes. E. All of these

35.

Part II Short essay. You must answer questions 36 and 37 and choose one more from the remaining three. Ten points each. 36. It is found that a toxin is more toxic when it is given in one large dose than when it is administered in small doses given at 6-8 hour intervals. It takes a larger total dose to produce the same effect when it is given in small increments than when the toxin is given as one large dose. Give at least three reasons to explain this phenomenon.

37.

Repair is an important process that may ultimately determine whether or not a chemical will manifest toxicity. Describe briefly the three levels of repair and give an example of each.

38.

Discuss four major anatomic and physiological properties that are responsible for the "blood brain barrier" in the central nervous system.

39.

Explain what an LD50 or ED50 is. Why are these values used to compare toxic responses of organisms to chemicals instead of lower or higher values?

40.

Describe four potential storage depots for toxicants. Provide an example of a storage mechanism or a type of toxicant that is stored in each depot.