Mercurio 1st Edition Test Questions & Answers

Chapter 1

1. Why are malformations of amphibians insufficient evidence for chemical toxicity?
2. How is toxicogenomics a form of cellular toxicology?
3. What toxicological information does the whole organism give toxicologists as exemplified by the injection of ¹⁴C –labeled esophageal carcinogen N-nitrosomethylbenzylamine?

Chapter 2

1. Why did Paracelsus believe that everything was poisonous?
2. How did the Pure Food and Drug Act open the way for the field of toxicology in the U.S.?
3. What did the book Silent Spring precede?

Chapter 3

1. What is a probit and why is it important in toxicology measurements?
2. What is an IC₅₀? Is it the same as an EC₅₀ or an LC₅₀?
3. What is an agonist and antagonist and how can both be toxic?
4. Which common medication that can be bought over-the-counter at a drug store are therapeutic as a dose and toxic as a dosage and which are therapeutic as a dosage but toxic as a dose?
5. Why is the log P or log K_OW an important factor in determining the bioavailability or toxicity of a compound?
6. Why is the MTD a controversial way of dosing an animal to assess toxicity?
7. Why might the toxicity of a substance actually drop with repeated exposures?
8. Why is TD₅₀ determined for human while the LC₅₀ is considered with environmental organisms?

Chapter 4

1. What is a QSAR? How does this apply to polychlorinated dibenzodioxins and dibenzofurans?
2. What is a hazard in risk assessment terms?
3. What is a LOEL, LOEC, NOEL and NOEC and how are they determined?
4. How is exposure determined? What is its usefulness?
5. Why is toxicokinetics and toxicodynamics the best but a very expensive approach to modeling a hazard and its risk?
6. What is an ADI?
7. What is the AUC?
8. What is a TWA?
9. What is a RgD?
10. How is carcinogenicity taken into account in risk analyses?

Chapter 5

1. What are aquaporins and how does toxicity result from disrupting their actions?
2. Using the Henderson-Hasselbalch equation, figure if someone accidently consumed the same concentration of the weak acid herbicide 2,4- dichlorophenoxyacetic acid, pK_a = 2.8, and the weak base herbicide atrazine, pK_a = 1.7, in the human intestinal pH of 6, which would be more absorbed on this factor alone.
3. Which transporter confers resistance to the cancer chemotherapy agent paclitaxel?
4. How do surfactants increase the permeability of membranes? These are sometimes used in pesticide mixtures to make the mixture miscible with water.
5. What is the Fenton reaction and how does this damage membranes?

Chapter 6

1. How does the Scatchard plot determine the potency of a given toxicant?
2. How does kainic acid cause toxicity to mammalian neuronal cells? What common local anesthetic agent do something opposite?
3. Why does targeting tyrosine kinase receptors lead to either cell proliferation or cell damage/death?
4. How can cAMP made by G-protein pathway be immunostimulatory or immunosuppressant?

Chapter 7

1. Why is the benzoyl-CoA reductase a key enzyme in the difference between the metabolism of anaerobic bacteria and facultative anaerobes?
2. What is the key reactant in the cytochrome P450 catalytic cycle and how is it formed?
3. What reactions reduce toxicity by CYPs and which ones lead to less toxic products?
4. Which inducers of CYPs lead to tolerance to medications while which ones cause more activation of procarcinogens?
5. Which enzyme class metabolizes/oxidizes various amines depending on its isozyme?
6. Which enzymes metabolize catecholamines and indolamines and their inhibition was used early on to help with depression, but also could lead to hypertension in cheese eaters?
7. Which enzymes metabolize arachidonic acid and inhibition of these enzymes led to the development (therapeutic medications) and adverse effects (toxicity) of NSAIDS?
8. Why does the metabolism of ethanol lead to a more toxic product to begin its conversion to a less toxic compound?
9. Indicate the possible phase 2 metabolites that may indicate the formation of a less toxic intermediate versus one that indicates a reactive intermediate.

Chapter 8

1. How does metabolism of allyl alcohol become a toxic product?
2. Why can a cationic electrophile be more toxic than its nonionic equivalent?
3. Why is benzene a leukemia agent when metabolized?
4. What kinds of toxic mechanisms does acetaminophen overdose cause?
5. Metabolism to a quinone imine damages the liver while the semiquinone imine metabolite damages the kidney by binding to protein. Acetaminophen also depletes glutathione and activates toxic signal transduction pathways.
6. What separates the effects of calcium from causing apoptosis to necrosis?
7. Indicate how an iron chelating agent can be a specific antidote and how that would work.

Chapter 9

1. What does the release of cytochrome c by mitochondria start?
2. What is the mitochondrial transmembrane electric potential?
3. What do cyanide and carbon monoxide toxicity share in common?
4. What do mammals and plant mitochondria share in common?
5. What role does the transmembrane electrochemical proton gradient play in chloroplast ATP synthesis?

Chapter 10

1. How was thimerosal’s (used in vaccine production) damage to the nuclear membrane assessed?
2. What kind of mutations does N-ethyl N-nitrosourea cause?
3. Why are PAHs involved in frameshift mutations?
4. How is the cis-dichloro, diaminoplatinum compound (cis-platinum) a cross-linking agent?
5. Why would interference with topoisomerase II cause clastogenesis?
6. What is the difference between genotoxic carcinogens and cell proliferation agents?
7. How is the Comet assay interpreted?

Chapter 11

1. 1. Why would polymorphisms of the OAT1B1 protein lead to liver cell hypersensitivity and polymorphisms of the MRP2 protein lead to liver cell hyposensitivity to the cholesterol lowering drug pravastatin?
2. How can a CYP polymorphism OR a GSTM polymorphism lead to an increase in toxicity of a compound?
3. People with polymorphisms in the ALDH1 gene don’t enjoy liquor. Why?
4. Women with the BRCA1 or BRCA2 gene polymorphism/mutation are known to have poor outcomes for prevention of breast cancer. How might alterations of other genes lead to similar prognoses?
5. Why do people with certain immune gene polymorphisms have dermal toxicity?

Chapter 12

1. What is malnutrition?
2. What does too little ascorbic acid cause? Excess?
3. What does vitamin A deficiency cause? Excess?
4. What does selenium deficiency cause? Excess?
5. What does calcium deficiency cause? Excess?
6. What antibiotic is known for causing calcium deficiency? What toxicities are elevated by this deficiency?
7. Sugar intake in the U.S. leads to a number of diseases. What may be there mechanisms of formation?

Chapter 13

1. Explain the skin absorption equation Ks = k_e x M[1-exp(-k_ex t)].
2. What are the models for small-molecular-weight absorption, high-molecular-weight absorption and protein absorption by the ocular route?
3. Why is the AUC rather than the concentration at one time point by oral administration used to calculate bioavailability?
4. What factors do the National Toxicology Program recommend to be included in a toxicokinetic study?
5. What is enterohepatic recirculation and how does it complicate modeling?
6. What is the problem with using the rat as a model of acetochlor or similar compound inhalation toxicity?
7. Why doesn’t paraquat have to be inhaled to damage the lung?
8. Why might a water soluble toxicant be as toxic via intravenous exposure as intramuscular or subcutaneous exposure while a hydrophobic toxicant may be initially less toxic via the nonvascular routes? What would the intraperitoneal route indicate?

Chapter 14

1. If an acid digestion is done on the brain of a corpse and steam is used to release the toxicants of interest, with what might this person might be poisoned?
2. If an athlete used an illegal performance-enhancing medication and this athlete’s samples were lost, what might still contain the drug weeks to a few months later?
3. If a person came in experiencing toxidromes consistent with changes in the anion gap and hepatic damage, which toxicants are consistent with these effects?
4. Liver enzymes found in the plasma are usually a sign of statin or acetaminophen toxicity but could be due to excess iron or other liver toxicants. What might separate the toxicity on a corpse but would not be highly recommended on a surviving person?

Chapter 15

1. Why does a strong solvent appear to give a burn?
2. What skin reactions involve T cells or proinflammatory release of cytokines from keratinocytes?
3. What type of acne is indicative of more serious internal toxicity?
4. Why do dogs develop a corneal opacity to 1,2-dichloroethane?

Chapter 16

1. Which substances are known to stain teeth, but not necessarily lead to other toxicity?
2. What toxic metal results in gingivitis but is not due to plaque formation or bacterial action on teeth?
3. What substance normally secreted into the intestinal tract cause ROS and RNS formation in the esophagus if GERD occurs?
4. Why does nickel target the jejunum?
5. What does chronic cocaine cause?
6. Can cancers of the exocrine pancreas be caused by ingestion of PAHs?
7. Why is allyl alcohol a model zone 1 toxicant of the liver while carbon tetrachloride would be a model zone 3 toxicant?

Chapter 17

1. What chemical formed by electrical discharges causes oxidant damage to the respiratory tract starting with the nasal epithelium?
2. Cancers of the larynx are fairly rare for most cigarette users, but marijuana smokers contract this disease. Why?
3. Why will vaping (nicotine electronically put into a vapor) increase the person’s response to other air pollutants similarly to a standard smoker of cigarettes?

(NNN) via α-hydroxylation pathways to reactive intermediates that form DNA adducts and subsequently lung cancer).

1. Why do metals that cause gill damage not only affect respiratory functions but also functions that appear in the mammal to be controlled by the kidney?

Chapter 18

1. How is methemoglobin not only a toxicity but a method for detecting other toxicants?
2. What effect does cadmium have on the vasculature?
3. Why does cardiomyopathy develop readily from exposure of the heart to cancer chemotherapy anthracyclines, ethanol, or the antiviral AZT?
4. Why is the heart so sensitive to potassium and calcium concentrations in the blood? Why do these change the ECG?

Chapter 19

1. How does benzene cause immune suppression similar to radiation?
2. Why are small molecules not necessarily recognized by the immune system?
3. Which interleukins recruit T4 helper cells or is produced by T4 helper cells to stimulate cytotoxic T cell clonal selection or antibody clonal selection?
4. What happens if a chemical or genetic abnormality eliminates or reduces Treg or Breg cells or both?
5. What is the effect of topic naphthalene on immunity?
6. Why are the presence of M1 macrophages an indication of acetaminophen toxicity in the liver while M2 macrophages indicates less toxicity?
7. When someone spills formaldehyde solution on the skin and a day or so later starts noticing a red area despite having washed most of it off, what likely is happening?
8. A person takes penicillin for the second time orally and develops a rash in the mouth, the tongues starts to swell, feels itchy and dizzy. Quickly it is hard to breath. What is happening?
9. Why are autoimmune reactions of blood cells (type II) or kidney glomeruli (type III) likely to come from chronic gold or mercury exposure?
10. Why do many cytotoxic agents cause immune suppression?

Chapter 20

1. What is the blood-brain barrier and how is it breached by agents such as 3-chloropropanediol?
2. How is the choroid plexus of interest in determining damage to the BBB?
3. How might calcium disruption cause brain toxicity?
4. How can protein disruption lead to CNS problems?

₃

1. What are examples of chemicals that alter gene expression to cause at least part of their neurotoxicity?

neurodegeneration (Al), and prolonged CNS depression (solvent exposures).

Chapter 21

1. Why is vitellogenin expression a measure of endocrine disruption?
2. What is a good model of thyroid disruption?
3. What discontinued persistent chlorinated pesticide affected GnRH?
4. The adrenal effects could just be a stress response. How can a scientist differentiate between stress and endocrine disruption in this organ?

Chapter 22

1. How does bisphenol A cause epigenetic developmental disruption?
2. How does BPA also affect early male development?
3. How can the organochlorine pesticide methoxychlor affect egg layers, such as amphibians?
4. Why might exposure to burn products from forest fires be problematic for reproduction?
5. What is the A/D ratio?

Chapter 23

1. Why does severe kidney damage always cause prerenal azotemia?
2. Why do cytotoxic cancer chemotherapy agents mainly damaging the vasculature?
3. How do aminoglycoside antibiotics such as neomycin cause kidney damage?
4. Why is the loop of Henle a problematic area for a number of compounds?
5. What is a marking feature of collecting duct damage?

Chapter 24

1. In a framework for comparative toxicity assessment of Figure 24-2, what are differences between calculating human versus ecosystem effects?
2. Why is concentration in air, water or soil models worst case in the U.S.?
3. Why is a plume model used in air, soils, and other dispersion calculations?

Chapter 25

1. Ammonia is known as a mitochondrial toxicant which results in neurotoxicity in humans. How do other species’ susceptibility indicate other actions of ammonia?
2. Which herbicides appear to be the most toxic to mammals? To plants?
3. Which insectides are mostly toxic to the insects and why? Which are toxic to insects and humans and may also affect bees?
4. Why are all fumigants toxic?
5. Why can cholecalciferol (vitamin D₃) be used as rodenticide or warfarin?

Chapter 26

1. What is CSE and how does it develop?
2. How does CS₂ markedly differ from methanol in its toxicity?
3. Why is CYP2E1 linked to the toxicity of highly chlorinated solvents?
4. Why is benzene a carcinogen, and toluene and xylenes mainly neurotoxins?
5. Why is hexachlorobenzene more like a dibenzodioxin rather than a bromobenzene?

Chapter 27

1. How is As toxicity manifested?
2. Why does Cd focus on the kidney for its toxic action?
3. Why is cobalt a nutrient and a toxicant?
4. Lithium is used to treat bipolar disease. What are its adverse effects?

Chapter 28

1. What is the difference between a simple vs. a chemical asphyxiant?
2. What are the effects of cadmium oxide?
3. Why is the size of asbestos so important in the toxicity to the tract. Is the asbestos or the body’s reaction to it that causes the problems?
4. The Fukushima nuclear meltdown workers were allow 250 mSv of radiation exposure and there was 570 PBq of ¹³¹I released from the plant. What are the concerns for long-term versus short-term problems associated with these exposures?
5. Why are alpha particles much more toxic to cells surrounding a source than beta or gamma irradiation?

Chapter 29

1. Based on its toxicity, why might triclosan be banned in the state of Minnesota?
2. Why are sewage effluents from cities considered one of the most potent source of estrogenic endocrine disruptors?

Chapter 30

1. Why might land-based snakes (crotalids) have a different venom composition than that of elapids or sea snakes?
2. Venom economy is a concern to desert animals. Why would they be likely to use their jaws or constriction rather than venom if possible?
3. Why is it important for a frog to secrete a poison onto its skin to prevent being eaten?
4. What is the proper origin of botulism toxin?
5. Moldy corn cannot be mixed with uncontaminated corn and sold for feed. Why not?

Chapter 31

1. Why is the rosary pea’s toxicity somewhat related to certain bacterial toxins?
2. Why are soybeans toxic if not heat-processed
3. Why is artificial licorice better for children than naturally-flavored licorice?
4. What part of plants usually contains drugs of abuse? Give examples and their properties.
5. What would vinca alkaloids have opposite effects to paclitaxel but both interfere with mitosis in cancer cells?