1. The antifungal drug ketoconazole specifically inhibits a cytochrome P450 isozyme responsible for the biotransformation of many drugs, among them midazolam. In a patient taking ketoconazole (200 mg/day PO), what would be the difference, if any, in this patient’s exposure (AUC0-24h) to midazolam if midazolam was administered intravenously (IV) vs. orally and why?
A) no difference in IV vs. oral exposure because oral bioavailability of midazolam is 100% and is not metabolized by enterocytes
B) increased exposure by the oral route because ketoconazole inhibits both the intestinal and hepatic P450 isozymes
C) decreased exposure by the oral route because ketoconazole increases midazolam export from enterocytes via P-glycoprotein.
D) decreased exposure by the IV route because ketoconazole preferentially inhibits P450 metabolism in enterocytes
2. In a reproductive toxicity study, what is the “fertility index”?
A) the percentage of live fetuses per litter
B) the percentage of attempted matings that result in pregnancies
C) the ratio of fetuses at 14 days gestation/total implantations)
D) the ratio of early fetal deaths/total implantations
3. What changes in serum enzyme levels are indicative of acute hepatocellular injury?
A) increased alanine aminotransferase and aspartate aminotransferase)
B) increased lactate dehydrogenase and decreased bilirubin
C) increased sorbitol dehydrogenase and lipase
D) increased 5′ nucleotidase and decreased urea nitrogen
4. What are the four core tester strains of Salmonella typhimurium used in the Ames (bacterial reverse mutation) assay?
A) TA 1535, TA 100, TA 1538, TA 98
B) TA 1540, TA 200, TA 1520, TA 80
C) TA 1548, TA 202, TA 1505, TA 92
D) TA 1536, TA 110, TA 1518, TA 85
5. The in vivo micronucleus test is often used in a standard battery of genetic toxicity assays. In this test, what do the observed micronuclei represent?
A) pyknotic nuclei from cells with decreased cytoplasmic to nuclear ratios
B) clumps of ribosomes and associated RNA fragments
C) membrane-bounded structures that contain chromosomal fragments or whole chromosomes
D) binucleated remnants of germ cells
1. A patient is admitted to the emergency room with decreased heart rate, blood pressure, body temperature, and pupil size. At intake, the patient appeared very sleepy, and a family member stated that he was recovering from recent surgery. Exposure to what class of agent explains the patient’s symptoms?
A) a narcotic analgesic
B) a non-narcotic analgesic
C) an antacid
D) a benzodiazepine tranquilizer
2. What food-borne exposure poses the greatest human-health risk worldwide?
A) chemical contaminants/adulterants
B) bacterial contamination
C) mycotoxins and molds
D) food additives
3. What point source is the most significant contributor to air pollution by mass in suburban areas?
A) cattle farms
C) electric power generation
D) waste disposal
4. Drug X is available as a 2.5% solution (w/v) in a 100-ml bottle. The desired intravenous dosage of this drug is 5 mg/kg body weight. What volume of drug should be injected if the patient weighs 50 kg?
A) 0.2 ml
B) 1.0 ml
C) 2.0 ml
D) 10 ml
5. Ethanol, retinoids, valproic acid, and the angiotensin converting enzyme (ACE) inhibitors share what primary characteristic?
A) induce liver toxicity
B) lower blood pressure
C) cause developmental toxicity
D) induce central nervous system effects
1. What form of ionizing radiation has the shortest range (i.e., travels the shortest distance in tissue) for the same initial energy?
A) alpha particle
B) beta particle
C) gamma ray
D) x ray
2. What property of beryllium-containing compounds is the reason they are not readily absorbed from the gastrointestinal tract?
A) they form insoluble phosphate precipitates at the pH of the intestinal tract
B) they are chelated by bile salts in the small intestine
C) their size prevents passage through cell membranes
D) they are converted to an oxide form
3. What is the mechanistic basis for cyclosporin A-induced cholestasis?
A) interaction with the cytoplasmic receptor, cyclophilin
B) inhibition of transcription of message (mRNA) for critical cytokines
C) induction of programmed cell death in centrilobular hepatocytes
D) inhibition of ATP-dependent transporter(s) in the bile canalicular membrane
4. What is the mechanism of neurotoxicity for strychnine?
A) glycine receptor antagonist
B) GABA uptake inhibitor
C) glutamate receptor agonist
D) blockade of muscarinic cholinoceptors
5. What condition will increase transport of a substance across the blood-brain barrier?
A) high ionization
B) strong binding to lipoproteins
C) strong binding to plasma proteins
D) cysteine binding
1. What is the default assumption in human-health risk assessment when male reproductive effects are observed in animal studies and no mechanistic data are available?
A) an agent that produces an adverse reproductive effect in experimental animals is assumed to pose a potential reproductive hazard to humans
B) a non-threshold is assumed for the dose-response curve for male reproductive toxicity
C) effects of xenobiotics on male reproduction are assumed to diverge radically across mammalian species
D) rodent reproductive processes are too dissimilar to those of humans to be used for human-health risk assessment
2. What is defined as “a measurable biochemical, physiological, or other alteration within an organism that indicates health impairment or disease”?
A) biomarker of exposure
B) biomarker of susceptibility
C) biomarker of effect
D) biomarker of disease
3. In what way is a point of departure (POD) from an animal study usually modified in order to determine a Reference Dose (RfD)?
A) an uncertainty factor of 100 is applied to the NOAEL in chronic animal studies
B) a risk factor of 1000 is applied to the NOAEL in chronic animal studies
C) a risk factor of 10,000 is applied to the NOAEL in subchronic animal studies
D) multiplying the NOAEL from chronic animal studies by 100
4. What is a limitation of the benchmark dose approach in risk assessment?
A) does not use the full range of doses and responses studied
B) cannot be used when a clear “no observed adverse effect level” (NOAEL) has already been attained
C) is based on a predefined benchmark response that is arbitrary
D) cannot be used to extrapolate beyond the range of administered doses
5. What characteristic of perceived risk renders it difficult to quantify?
A) rarely incorporated into risk communication decisions
B) based on the precautionary principle
C) highly influenced by factors such as familiarity and controllability
D) too subjective
1. What is the expected response of an individual exposed to a single absorbed dose of 10 rads (0.1 Gy) of whole body X-irradiation?
A) severe bone marrow depression
B) permanent sterilization
C) no adverse response
2. What form of mercury was the cause of Minamata Bay disease?
A) mercuric salts
B) mercurous salts
C) organic mercury
D) elemental mercury
3. What was the regulatory response to the Delaney clause?
A) permitted most food additives to be declared generally recognized as safe (GRAS)
B) prohibited EPA from setting safe exposure levels for environmental carcinogens
C) prohibited FDA from approving food additives found to cause cancer in animals
D) was applied only to food additives demonstrating human evidence of carcinogenicity
4. What does a threshold limit value-time weighted average (TLV-TWA) for a chemical represent?
A) an airborne concentration of a chemical that can never be exceeded during an 8-hour workday
B) a mean airborne concentration of a chemical believed to cause no adverse health effects to workers exposed for 8 hours/day, 40 hours/week
C) an airborne concentration of a chemical that cannot be exceeded for longer than 15 minutes during an 8-hour workday
D) An acceptable mean airborne concentration of a chemical established by the Occupational Safety and Health Administration (OSHA)
5. What is the target organ of streptomycin-induced toxicity?