The sample exam questions provided are representative of the new exam format that was implemented in 2017 and updated in 2022.

Domain I: Conduct of Toxicology Studies

1. 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

2. 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

3. 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

4. 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

5. What is the target organ of streptomycin-induced toxicity?

A) eye
B) heart
C) ear
D) liver

Answers to Domain I

1. B
2. A
3. A
4. C
5. C

Domain II: Mechanistic Toxicology

1.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

2. 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

3. 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

4. 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

Answers to Domain II

1. A
2. D
3. A
4. D

Domain III: Risk Assessment

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. 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
D) vomiting

3. 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

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) 1.2 ml
C) 2.0 ml
D) 10 ml

5. 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

Answers to Domain III

1. B
2. C
3. C
4. D
5. C

Domain IV: Applied Toxicology

1. 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

2. 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

3. What point source is the most significant contributor to air pollution by mass in suburban areas?
A) cattle farms
B) transportation
C) electric power generation
D) waste disposal

4. 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

Answers to Domain IV

1. C
2. A
3. B
4. B