Casarret & Doulls Flashcards
What is Descriptive Toxicology?
The emphasis is on the testing of toxicants, typically on animals. It focuses on the dose–response relationship and extrapolation to humans.
What is Mechanistic Toxicology?
Looks at how the agent induces its biochemical or physiological effect on the organism, that is, modes
of action. Biochemical and Molecular Toxicology is a synonym
for this branch.
What is Clinical Toxicology
This branch’s focus is on the effects of drugs
and other chemicals on humans, particularly, but also on other
animals.
What is Forensic Toxicology?
Concerned with the cause of death from toxic
agents, often in instances of drug abuse or misuse
What is Environmental Toxicology?
Investigates the effects of toxicant exposures on the general environment and living organisms therein. Thus,
pollution of air, water, and soil, and effects on plants and wildlife
would fall within this branch. Ecotoxicology, a more specialized
area, is devoted to the effects of toxic chemicals on populations,
communities, and terrestrial, freshwater, and marine ecosystems.
What is Occupational Toxicology?
Deals with the study of chemical and
other agents in the workplace, worker exposures, safety and
health, and standard setting.
What is Regulatory Toxicology?
Focuses on ways in which humans and the
environment can be protected from toxic effects, through regulations and standard setting. Considers scientific decision-making
within a societal and legal framework. Relies heavily upon risk
assessment.
What is Toxicogenomics?
Concerned with the compilation and synthesis of information regarding gene and protein expression in
order to understand molecular mechanisms involved in toxicity. Toxicogenomics calls upon proteomics, metabolomics, and
transcriptomics to identify biomarkers that predict toxicity and
genetic susceptibility to harmful substances
What is Computational Toxicolo9gy?
Deals with the use of modern computational approaches and information technologies to elucidate mechanisms of toxicity. May also be referred to as
toxicoinformatics
Aflatoxin is an example of what fungus that grows on foods such as corn and nuts? Exposure cases an increase in what clinical disease?
Aspergillus; liver cancer
Cloracne, is observed in individuals exposed to what chemical?
TCCD (2,3,7,8-tetrachlordibenzo-p-dioxin)
Which regulatory body is responsible for enforcing the Comprehensive
Environmental Response, Compensation and Liability Act
(CERCLA, later revised as the Superfund Amendments
Reauthorization Act [SARA]), more commonly called the
Superfund Act
EPA
What regulatory body is responsible for conducting research and making recommendations for the prevention of
work-related injury and illness, making occupational toxicology
an important component of regulatory toxicology
The National Institute
for Occupational Safety and Health (NIOSH) as part of the Centers
for Disease Control and Prevention (CDC) in the Department of
Health and Human Services (DHHS)
What is Chemical idiosyncrasy?
The abnormal reactivity of an
individual to a chemical based on its genetics or other individual
sensitivity factors. Idiosyncratic reactions can occur in any organ system; however, the skin, liver, hematopoietic, and immune systems are the
most often affected
What are the differences between additive, synergistic, potentiation and antagonism effcets?
An additive effect occurs when the combined responses of two
chemicals is equal to the sum of the responses to each chemical given alone.
A synergistic effect is observed when the combined responses
of two chemicals are much greater than the sum of the response
to each chemical when given alone.
Potentiation occurs when one substance does not produce any
toxicity on a particular tissue or system but when added to
another chemical makes that chemical much more toxic.
Antagonism occurs when two chemicals administered together
interfere with each other’s actions or one interferes with the
action of the other.
Define Dispositional tolerance.
Occurs when the amount of chemical
reaching the site of action decreases over time, leading to the
reduced responsiveness of the tissue to stimulation.
A chemical known to produce dispositional tolerance is phenobarbital.
The barbiturate, phenobarbital, produces tolerance to itself
by increasing the expression of enzymes in the liver that are
responsible for its biotransformation to pharmacologically
inactive products, a process known as “biotransformation
enzyme induction.”
What are the two major factors that influence toxicity as it relates to the exposure of a specific chemical?
Route
Duration & Frequency
What is a Threshold of toxicological concern (TTC)?
TTC suggests
that there are levels of exposure for chemicals below which the
risk to human health is not appreciable. It was first proposed in
the context of food safety.
What shape is a nonmonotonic dose-response curve?
For natural or endogenous chemicals that
are required for normal physiological function and survival (e.g.,
vitamins and essential trace elements such as chromium, cobalt,
zinc, manganese, and selenium), the “graded” dose–response relationship in an individual over the entire dose range can be U-shaped
On the non-monotonic dose response curve, what is the region of homeostasis?
The dose range that doesn’t induce deficiencies or toxicities. It lies below the threshold for adverse responses.
What is assessed in the therapeutic index?
Toxic dose / effective dose
TD50/ED50
What is assessed in the margin of safety?
TD1/ED99
No cumulative effect would be 1, where a cumulative effect would be 90.
What is the differences between efficacy and potency?
Efficacy is an assessment of the extent to which a chemical can
elicit a response and is often interpreted using the ordinate axis
(or y-axis). By comparison, the potency is determined by the range
of doses (on the x-axis) over which a chemical produces increasing responses.
What size/dimension of inhaled particles would favor their deposition in the respiratory (alveolar)
region of the lung?
A. ≥2.5 micrometers in diameter
B. <0.01 micrometers in diameter
C. 1 x 200 micrometer elongated fibers
D. between 0.01 and 2.5 micrometers in diameter
Answer: D
Explanation and Reference:
Particles reach the alveolar region on the lung by sedimentation and diffusion. Sedimentation is not
favorable for particles ≤0.5 μm aerodynamic diameter but diffusion is favorable for this dimension
down to 0.01 μm. Particles >2.5 μm would be trapped in the upper airway by impaction. An
elongated fiber would be trapped in the bronchial tree by interception. C&D 8th, pp. 702-703
Particles ≤100 nm in at least one dimension are nanoparticles. When inhaled, why do these particles
generally result in greater pulmonary inflammation than an equal mass of larger size particles?
A. nanoparticles have a significantly greater surface area to mass ratio
B. nanoparticles deposit deeper in the respiratory tract than larger sized particles
C. nanoparticles are generally more water soluble than larger particles
D. nanoparticles reduce the clearance capability of alveolar macrophages
Answer: A
Explanation and Reference:
The toxicity of nanoparticles is attributed primarily to the increased surface area that can generate
secondary reactions (oxidative stress) or carry co-pollutants into the lung. They have no effect on
macrophages but may not be effectively cleared by these cells. They do not necessarily deposit
deeper in the lungs, depending on their shape. Since most nanoparticles are carbon fibers or metals,
it would be incorrect to characterize them generally as “water soluble.” C&D 8th, p. 703
For what type of toxicity study is the hen (chicken) used as the test species in the registration
package for organophosphate insecticides?
A. teratogenicity
B. acute delayed neurotoxicity
C. 90-day oral toxicity
D. acute oral toxicity
Answer: B
Explanation and Reference:
Chickens are a sensitive species for ChE inhibition. The adult hen is the required animal model for
this assay under OECD Guideline 419 and US EPA Health Effects Test Guideline OPPTS 870.6100.
C&D 8th p. 938, Table 22-7
What modification of the LD50 assay is described by the following? Animals are dosed one at a time,
starting at an estimated LD50 dose. If the first animal survives, the next one receives a higher dose. If
the first animal dies, the next one receives a lower dose. The spacing of dosing generally is adjusted
by a factor of 3.2.
A. the up-and-down method
B. approximate lethal dose method
C. the acute toxic class method
D. the fixed dose procedure
Answer: A
Explanation and Reference:
In the up/down method the animals are monitored for overt signs of toxicity until death. Methods A,
B, and D are all modifications of the LD50 assay designed to reduce animal numbers and/or
increase quality and quantity of information collected. Hayes 6th p. 1152
A 20 kg child has consumed 300 mg of caffeine in a dietary supplement. The volume of distribution
(Vd) per kg of body weight for caffeine is 0.75 liter/kg. What is the child’s estimated initial blood level,
assuming 100% gastrointestinal absorption?
A. 50 mg/liter
B. 20 mg/liter
C. 5 mg/liter
D. 200 mg/liter
Answer: B
Explanation and Reference:
Vd= Dose/Co, where Co is initial concentration assuming instantaneous equilibration. Rearranging
and solving for Co yields a new equation, Dose/Vd = Co. The dose (or dosage) is 300 mg/20 kg = 15
mg/kg divided by the Vd, 0.75 liter/kg = 20 mg/L. C&D 8th p. 372
Calculate the achieved dosage in mg/kg/day of a chemical fed to rats at a concentration of 0.5%
(5000 ppm) in the diet. The rats had a mid period group mean body weight of 250 g and ate 210
g/week of the chemical diet admixture.
A. 600
B. 42
C. 60
D. 420
Answer: A
Explanation and Reference:
5000 ppm is 5000 mg/kg diet x 0.030 kg diet/day (210 g/wk divided by 7 = 30 g or 0.030 kg diet/day)/
0.25 kg rat = 600 mg/kg-day. Hayes 6th, p. 1217-1220
What would be considered an advantage of the Cohort epidemiological study design?
A. requires a small number of subjects
B. suitable for rare diseases
C. yields incidence and risk rates
D. short follow-up period with subjects
Answer: C
Explanation and Reference:
Cohort studies evaluate multiple effects following exposure. They are prospective studies yielding
incidence and risk rates. The follow up can last years, in contrast to a cross-sectional study that
yields quick results. Case-control studies are best for rare diseases and use small numbers of
subjects. C&D 8th p. 131, Table 4-5
100 mg of Drug X is administered by rapid IV bolus. Assuming conditions of a one compartment
model, what is the apparent volume of distribution (Vd) given a half life of 10 hours and an initial
plasma concentration of 4 mg/L?
A. 25 L
B. 10 L
C. 20 L
D. 5 L
Answer: A
Explanation and Reference:
Vd can be in units of L or L/kg. The simple formula is Vd=Dose/Co, where dose can be in mass (mg)
or relative mass (mg/kg) and Co is the initial concentration in mass/volume (mg/mL). In this question,
Co and dose are given, and applying the formula, 100 mg/4 mg/L=25 L. The t½ in the question is a
distractor. One could also calculate Vd knowing t½ and Clearance. C&D 8th pp. 371-373.
Conventional approaches to toxicity testing of pharmaceuticals may not be appropriate for
biopharmaceuticals. In developing a monoclonal antibody in accordance with ICH S6 guidelines, what
is the first consideration when designing IND-enabling in vivo safety studies?
A. selecting a dose level producing clear toxicity
B. assuring the test article is non-immunogenic
C. understanding the mode of action
D. choosing a relevant test species
Answer: D
Explanation and Reference:
Preclinical safety testing should consider: (1) Selection of the relevant animal species; (2) age; (3)
physiological state; (4) the manner of delivery, including dose, route of administration, and treatment
regimen; and (5) stability of the test material under the conditions of use in that order. Reference:
ICH S6, Preclinical Safety Evaluation of Biotechnology-derived Pharmaceuticals, July 1997, pp.2-8.
(specifically Section 1.2, Para 2)
What IND-enabling preclinical studies are recommended in the ICH S6 and M3 guidelines for both
monoclonal antibody and small molecule pharmaceutics?
A. immunogenicity studies
B. tissue cross reactivity studies
C. pharmacokinetic and toxicokinetic studies
D. in vitro genotoxicity studies
Answer: C
Explanation and Reference:
Single and multiple dose pharmacokinetics, toxicokinetics, and tissue distribution studies in relevant
species are recommended for both types of programs. Immunogenicity and tissue cross reactivity
would be unusual for a small molecule and genotoxicity studies are generally not applicable to
biotechnology products. ICH guidelines S6 (Section IV.B.(4.2.1) and IV.G.(4.7) and M3; also Hayes
6th, pp. 332-333, 355
In evaluating differences between mean values of clinical chemistry variables from an animal toxicity
study on Day 1 vs. Day 14, statistical analyses are used, and a p-value of <0.05 for several
comparisons were derived. What does a p-value of <0.05 mean?
A. the differences between the variable means are statistically and biologically significant
B. the significant differences between means were caused by the treatment
C. the probability that the the observed response had no effect is less than 1 in 20
D. the probability that the observed response had no effect is less than 1 in 20
Answer: C
Explanation and Reference:
The significance level is the chance of obtaining a false positive result due to sampling error (known
as a Type I error). It is usually set at 5%, although lower levels are sometimes specified. In other
words, it is the probability that the null hypothesis is true. Statistical significant tells the investigator
nothing about biological significance or whether the differences are true or not. Hayes 6th, p. 377
In risk assessment, what results can be obtained by using DNA microarrays in toxicology studies?
A. many genes can be evaluated simultaneously to detect patterns of response to a toxicant
B. detection of differential gene expression, eliminating the need to test the toxicant in whole animals
C. changes in gene expression that can be precisely correlated to changes in organ function
D. measurements of gene expression that can be precisely quantified following exposure to a
toxicant
Answer: A
Explanation and Reference:
Sophisticated analysis of microarrays can be used to analyze patterns of gene espresssion between
comparative sets of samples. These analyses can be linked to functional intepretations and classic
toxicological endpoints. C&D 8th, pp. 140, 1281-1282
In evaluating dose-response relationships, the benchmark dose approach offers what advantage over
the NOAEL approach?
A. establishes a mode-of-action for threshold effects
B. provides greater certainty with fewer animals
C. establishes a mode-of-action for nonthreshold effects
D. includes a measure of variability in the data set
Answer: D
Explanation and Reference:
The benchmark dose includes a measure of variability whereas the NOAEL does not. It also allows
consideration of the shape of the entire dose-response curve and permits a specified benchmark
response (BMR) level for RfD calculations. C&D 8th, p. 134-135
The following dosages of a test drug were administered to male rats by oral gavage daily for 28 days:
10, 50, and 100 mg/kg. The only observed toxicity was focal hepatocyte necrosis, observed at the
100-mg/kg dose level. Based on these data, what is the no-observed adverse effect (NOAEL)?
A. 10 mg/kg
B. greater than 50 mg/kg, but less than 100 mg/kg
C. 100 mg/kg
D. 50 mg/kg
Answer: D
Explanation and Reference:
The NOAEL is a professional opinion based on the design of the study, indication of the drug,
expected pharmacology, and spectrum of off-target effects. It requires a decision of what findings are
adverse to the test system under the conditions of study.
http://www.fda.gov/CDER/guidance/5541fnl.pdf “Guidance for Industry Estimating the Maximum Safe
Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers”; C&D 8th p. 134
(also C&D 9th, pp. 36-37)
What analytical method would be used on tissue samples to detect drug-induced alterations in
specific RNA sequences?
A. western blot
B. northern blot
C. eastern blot
D. southern blot
Answer: B
Explanation and Reference:
The northern blot is a technique to study gene expression by measuring the cellular production of
RNA. Hayes 6th p. 303
What in vivo assay is designed and used primarily for the detection chromosomal breakage
(clastogenicity)?
A. Drosophila sex-linked recessive lethal assay
B. rodent bone marrow micronucleus assay
C. TK assay in mouse lymphoma cells
D. chromosomal aberration assay in human lymphocytes
Answer: B
Explanation and Reference:
The rodent micronucleus test is the only in vivo assay for detecting clastogenicity. Two chromosomal
aberration assays, one in CHO cells and the other in human peripherla blood lymphocytes, are also
used, but they are in vitro assays. The mammalian-microsome reverse mutation assay is, like the
Ames assay, is intended to detect mutagenicity (e.g. point mutations, forward mutations). Hayes 6th,
pp. 1258-1260, Table 25.4
Fluorescein-conjugated nucleic acid probes are used as tools in a technique called Fluorescence In
Situ Hybridization (FISH). For what primary purpose is this technique used in genetic toxicology?
A. facilitates counting micronuclei in polychromatic erythrocytes
B. locates point mutations in mammalian chromosomes
C. more accurately quantitates sister chromatid exchanges
D. facilitates cytogenetic analysis by “chromosome painting”
Answer: D
Explanation and Reference:
FISH uses fluorescent probes to bind and visualize nucleic acids with a high degree of similarity.
C&D 8th, pp.465-466 and 471-472
A treatment-related increase in the number of micronucleated cells in a genotoxicity study indicates
what type of adverse effect?
A. chromosomal translocation
B. toxicity to bone marrow cells
C. DNA point mutations
D. clastogenicity and/or aneuploidy
Answer: D
Explanation and Reference:
The micronucleus assay measures the number or chromatic erythrocytes, which are remnants of
clastogenic DNA damage in mature red blood cells. The technique also detects aneuploidy. C&D 8th,
p.466-467
What animal model in considered the best predictor of dermal absorption of chemicals for humans?
A. rat
B. pig
C. mouse
D. rabbit
Answer: B
Explanation and Reference:
Historical research has shown that, in general, chemical penetration of the human skin is similar to
that of a pig or monkey, and much slower than that of the rat and rabbit. C&D 8th p. 167
The single-cell gel electrophoresis assay (Comet test) is used to detect what genotoxic endpoints?
A. single and double strand DNA breaks in cells and tissue
B. point mutations in bacterial and mammalian cells
C. sister chromatid exchanges (SCE) in mammalian cells
D. aneuploidy in bone marrow cells
Answer: A
Explanation and Reference:
The COMET assay measures isolated DNA fragments using a gel electrophoresis method; smaller
fragments migrate further in the gel and length can be measured. C&D 8th p. 460 and Table 9-2
During a reproductive and developmental toxicology study in mice, a statistically significant and dose
related decrease in the number of live fetuses per litter was determined following mating of treated
males and naive, untreated females. No decrease in mating and fertility ratios or evidence of preimplantation
loss was found. To what would you attribute the decreased number of live fetuses per
litter?
A. a decrease in male libido
B. a dominant lethal mutation in sperm
C. a decrease in the number of ova fertilized
D. a decrease in viable sperm per male
Answer: B
Explanation and Reference:
From the information provided, there are no adverse effects of treatment on mating, fertility, and
implantation. The scenario is one of post-implantation loss, and in this case toxicity to sperm is
suspect. A test specific for this effect is known as the Dominant Lethal Male Assay for mutagenicity.
Hayes 6th, pp. 440-443, 1623
In the evaluation of lung exposure to airborne particulates, what is considered the measure of the
inspired respiratory volume?
A. forced expiratory volume in 1 sec (FEV1)
B. total inspiratory capacity (IC)
C. breathing rate (f) multiplied by tidal volume (Vt)
D. vital capacity (VC) including the functional residual capacity (FRC)
Answer: C
Explanation and Reference:
Breathing rate multiplied by tidal volume determines minute ventilation, and increased minute
ventilation in a polluted atmosphere increases the deposition of toxic materials. C&D 8th, p.699
The murine local lymph node assay (LLNA) has been used as a substitute for the guinea pig
maximization test (GPMT). What is the measurement endpoint in the LLNA?
A. ear edema using Draize criteria
B. size of the submandibular lymph nodes
C. H3 thymidine uptake into proliferating lymphocytes
D. ear erythema using Draize criteria
Answer: C
Explanation and Reference:
The murine LLNA measures H3 thymidine uptake into proliferating lymphocytes of the lymph nodes
draining the injection site. The LLNA is a measure of induction; inflammation and erythema are
measures of elicitation. Measuring the size of the submandibular lymph node is too non-specific and
variable to be useful. C&D 8th, p.586
What characteristics of a xenobiotic would favor dermal absorption?
A. ionic, low molecular weight
B. hydrophobic, low molecular weight
C. nonionic, high molecular weight
D. hydrophilic, low molecular weight
Answer: B
Explanation and Reference:
Compounds that are lipophilic and of low molecular volume are most likely to penetrate the skin. C&D
8th, p. 166
What is the disadvantage of using renal component systems (e.g., slices, isolated tubules or isolated
perfused kidneys) in mechanistic toxicology research?
A. limited viability and correlation to whole-animal
B. variables from single-animal sources cannot be controlled
C. tubular transport studies cannot be performed
D. specific nephron segments of interest cannot be isolated
Answer: A
Explanation and Reference:
Freshly prepared cell models have limited lifespan (2-24 h); whereas, primary renal cell cultures or
cell lines may last several weeks. With all models, however, all models exhibit less differentiated
functions and similarity to the in vivo system. C&D 8th p. 778
What bacterial strain included in the core strains of the Ames assay can specifically detect mutagens
that induce frame-shift mutations, other small deletions, and some complex mutations?
A. TA97
B. TA102
C. TA1538
D. TA100
Answer: C
Explanation and Reference:
TA1538, along with TA98, can measure frameshift, small deletion, and some complex frameshift
mutations. C&D 8th, p. 462, Table 9-3
What is the most common spontaneous neoplasm in control male Fischer (F344) rats observed in
two-year bioassays?
A. liver adenoma/carcinoma
B. thyroid c-cell adenoma/carcinoma
C. testicular interstitial cell tumors
D. pituitary adenoma/carcinoma
Answer: C
Explanation and Reference:
Based on the NTP 2-year rodent carcinogenicity studies, testicular interstitial cell adenomas are the
most commonly found neoplasm in controls. C&D 8th, p. 38, fig. 2-15
What two genotoxicity assays would detect point mutations?
A. in vivo micronucleus assay and in vitro metaphase analysis in CHO cells
B. in vitro sister chromatid exchange assay and in vitro micronucleus assay
C. in vitro unscheduled DNA synthesis and in vivo mouse heritable translocation assay
D. in vitro bacterial reverse mutation (Ames) assay and forward mutation assay with mouse
lymphoma L5178Y cells
Answer: D
Explanation and Reference:
The Ames test (Salmonella typhimurinum), in particular, strains TA100 and TA1538, and the mouse
lymphoma assay detect point (substitution) mutations. C&D 8th, pp.425-426, Table 8-21 and pp. 461-
463, Table 9-3
In reproductive/developmental toxicology, what is the “gestation index”?
A. percent of mated females that deliver viable litters
B. percent of matings resulting in pregnancy
C. percent animals born that survive four or more days
D. percent of animals that survive the 21-day lactation period
Answer: A
Explanation and Reference:
The gestation index is one of the four primary variables that are of interest in any reproduction study
and is defined as given in the correct foil (C). The other three variables are the fertility index, the
viability index, and the lactation index. Hayes 6th, p. 440
The Comet Assay is used for what type of assessment?
A. evaluating serum neurotoxic esterase activity
B. monitoring carbon monoxide exposure in red blood cells
C. measuring DNA damage using single-cell gel electrophoresis
D. electrophoretic measurement of sperm motility prior to fertilization
Answer: C
Explanation and Reference:
COMET measures DNA damage in variable sections that create “tails” that can be measured to
determine extent of DNA damage in tissue of concern. C&D 8th, p.460
What is the experimental unit in a “Segment II” (ICH S5A Stage C) rat teratology study for the
purpose of statistical analysis (i.e., basic unit of comparison)?
A. litter or mating pair
B. individual live pups born
C. treated, fertile maternal animal
D. non-viable pups born
Answer: A
Explanation and Reference:
The primary focus of the Segment II study is to evaluate viability and morphology of the conceptus
prior to birth. When employing statistics, the mating pair or litter, not the fetus or neonate should be
used as the basic unit of comparison. ICH S5A(R3), Section 8.2, Statistics (2020)
What are the primary purpose and limitation of juvenile toxicology studies for pharmaceutical and
biotechnology products?
A. they are required for all new drug but not pesticide registration
B. they assess safety and efficacy but not risk
C. they assess the safety but not efficacy of a product .
D. they assess the efficacy but not safety of a product
Answer: C
Explanation and Reference:
Juvenile toxicology studies may be requested by the FDA to evaluate safety under pediatric
conditions. Hayes 6th, pp. 362-363
What genetic toxicology assay measures not only mutagenic but also recombination, deletion and
aneuploidy endpoints?
A. mouse micronucleus test
B. mouse lymphoma assay
C. Ames assay
D. comet assay
Answer: B
Explanation and Reference:
The mouse lymphoma assay has been used traditionally as a core test because it can serve as an in
vitro measure of both gene mutation and chromosomal aberrations. This is because mutations of the
target gene (TK) can be induced by either base pair substitution at the mutant site or by deletions of
the allele through chromosome breakage. The Ames assay measures reverse mutations in bacteria;
the micronucleus test and Comet assay measure clastogenicity. C&D 8th, p. 463 and Hayes 6th p.
1186
Intraocular melanin is involved with drug and environmental chemical toxicity to the retina by what
mechanism?
A. melanin has low binding affinity for most environmental chemicals
B. melanin is not located intraocularly
C. binding PAHs, chloroquine, and heavy metals.
D. melanin is depleted in the uveal tract between sclera and retina
Answer: C
Explanation and Reference:
Intraocular melanin exists in multiple regions of the eye, has a high affinity for chloroquine, heavy
metals, including lead, and other drugs where they can accumulate, and then are released slowly.
C&D, 8th, pp. 52, 780-785
The European Union banned all animal testing for what product category after 2009?
A. organohalogens
B. cosmetics
C. preservatives
D. petrochemicals
Answer: B
Explanation and Reference:
Under the seventh amendment to the EU cosmetics directive, the use of animals in safety
assessment for cosmetics is not permitted after 2009. There are no such proscriptions by the EU or
any other jurisdiction for the safety testing of organo- halogens, petrochemicals, or preservatives.
Hayes, 6th, p.1259
To demonstrate definitively that a chemical has the potential to act as a teratogen in rats, when during
gestation would you expose the dam?
A. during organogenesis
B. pre and post fertilization of the female
C. during the implantation period
D. throughout the entire gestation period
Answer: A
Explanation and Reference:
Teratogens are most effective when administered during organogensis (Day 7 to 17 in the rat). C&D
8th, p. 36 and ICH S5(R3), 2020, Annex 1: In Vivo study designs, Section 1.1.2.3, Table 3
What actions must be included when assessing embryo-fetal developmental toxicity under ICH S5?
A. examination of weanlings for gross and visceral abnormalities
B. treatment of male and female rodents for 60 days to assure implantation
C. assessments of resorptions, fetal body weights, and fetal malformations
D. assessments of neurobehavioral deficits incurred during prenatal exposure
Answer: C
Explanation and Reference:
These are needed to determine extent of unsuccessful implantations, predictive in fetal toxicity, and
diagnostic for teratagens. ICH S5(R3), 2020, Annex 1 In Vivo study designs, Section 1.1.2.3, Table 3
The presence of growth retardation, malformations and embryo lethality are commonly considered
with what test?
A. Segment I: fertility and general reproduction study
B. Segment III: perinatal study
C. OECD: Extended one-generation reproductive toxicity study
D. Segment II: teratogenicity study
Answer: D
Explanation and Reference:
The endpoints for the Seg II study are viability and anatomy of fetuses prior to birth. This is the
classic study for the detection of chemical teratogens where the dams are exposed from implantation
(or mating) to the end of organogenesis (or term). C&D 9th pp. 568-570 and Table 10-7.
The potential for xenobiotic-induced embryo-fetal developmental toxicity is best evaluated during
what gestational period in the rat (where conception=gestation day 0)?
A. gestation days 0-21
B. gestation days 6-17
C. gestation days 0-5
D. gestation days 6-21
Answer: B
Explanation and Reference:
Gestational days 6-17 is the primary period of organogenesis in rodents. This is the period of
development that is highly sensitive to teratogenesis. C&D 9th, pp. 554-55 (Table 10-4) and pp. 568-
570 and Table 10-7; also ICH S5 (R3) 2020 Section 1.1.2.3, Table 3.
Particle deposition by impaction is most prevalent in what region of the human lung?
A. first-generation tracheobronchial
B. bronchial tree
C. bronchiolar-alveolar
D. naso-pharyngeal
Answer: A
Explanation and Reference:
The deposition of particles in the respiratory system occurs either by interception, impaction,
sedimentation, or diffusion. As a result of inertia, particles between 2.5 and 10 μm in aerodynamic
diameter would be expected to deposit in the first branches of the upper airway. There is a trick to
this question. Particles > 10 μm would be deposited by impaction in the nose and oropharynx but
these regions are outside the lung. C&D 9th, pp. 804-805.
What feature is common to all four types of hypersensitivity reactions?
A. prior antigenic exposure
B. production of IgG
C. the generation of T cells
D. production of IgE
Answer: A
Explanation and Reference:
Prior antigenic exposure and formation of a protein-hapten conjugate is the common antecedent to all
four hypersensitivity-type reactions. C&D 9th, pp. 689-694, Fig. 12-22.
What in vivo assay measures only the induction phase of chemical sensitization?
A. the guinea pig maximization assay
B. the Draize test
C. the mouse local lymph node assay
D. the Magnusson-Kligman test
Answer: C
Explanation and Reference:
The murine local lymph node assay measures mitogenesis of immune cells in the mouse lymph
nodes following stimulation. It is the only assay that measures only the induction phase of
sensitization. All other require a second exposure and measurement of the elicitation phase. Hayes,
5th, p. 11102.
Alternative non-animal methods for testing the potential for chemicals to cause topical injury to the
eye have been developed by an international consortium and adapted by several regulatory
agencies. What animal test do these alternative methods replace?
A. the Draize test in rabbits
B. the Hay’s test in mice
C. the maze test in rats
D. the gaze test in primates
Answer: A
Explanation and Reference:
The correct answer is the Draize test in rabbits. This had been the standard since the 1940s but has
been criticized in the 21st Century for high inter-laboratory variability, subjective scoring, poor
predictive value, and for causing undue pain and distress to the test animals. The gaze test is used
to evaluate the ability to generate and hold a steady gaze without drift or gaze-evoked nystagmus.
This is a test used in humans and other primates. The maze test is used to test memory, cognition,
and behavior, commonly in rats. Hay’s test is a method for detecting bile salts in urine in any species.
C&D 9th pp. 885-886.
Reticulocytosis following high therapeutic daily doses of a drug is most characteristic of what
response?
A. a drug-induced normal physiologic response
B. drug-induced red blood cell destruction.
C. drug-induced polycythemia
D. drug-induced aplastic anemia
Answer: B
Explanation and Reference:
In cases of drug-induced red cell destruction, reticulocyte count can be useful in the diagnosis,
because increased destruction is usually accompanied by an increase in reticulocytes (young
erythrocytes) into the circulation. Reticulocytosis would not be considered normal drug response, and
polycythemia would be expected to decrease the production of new red cells. In the case of aplastic
anemia, the bone marrow would be unable to make a response; hence, reticulocytosis would not
appear. C&D 9th, p. 496-598
Chemicals such as chloramphenicol, phenylbutazone, and phenytoin can cause a condition known as
aplastic anemia. What is the specific cellular target of these chemicals?
A. colony forming unit-erythrocyte (CFU-E)
B. colony forming unit-granulocyte (CFU-G)
C. polymorphonuclear cells (PMN)
D. hematopoietic stem cell (CFU-S)
Answer: D
Explanation and Reference:
Aplastic anemia occurs through destruction of RBC stem cells in the bone marrow. C&D 9th pp. 598-
599
What cellular enzyme biomarkers in blood indicate the possibility of liver damage?
A. lactate dehydrogenase and liver phosphodiesterase
B. mitochondrial pyruvate oxygenase and creatine kinase
C. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
D. sorbitol dehydrogenase and serum oxygen transferase
Answer: C
Explanation and Reference:
Alanine aminotransferase and aspartate aminotransferase are considered two of the standard clinical
chemistry tests used in preclinical toxicology studies as indices of hepatocellular injury. Lactate
dehydrogenase is not liver specific, and liver phosphodiesterase is not a biomarker of toxicity. While
sorbitol dehydrogenase can be used to indicate hepatocellular injury, it is not a standard test and is
therefore not recommended. Oxygen transferases are not indicators of liver toxicity nor are
mitochondrial pyruvate oxygenases. Creatine kinase is a biomarker for cardiac toxicity. C&D 9th pp.
732-733
Clinical assessment of drug-induced liver injury using Hy’s Law considers what test results?
A. >3-fold increases in serum ALT and >2-fold increases in total bilirubin
B. >3-fold increases in ALT, AST, and ALP without increased total bilirubin
C. >3-fold increases in ALT, AST and >2-fold increases in total cholesterol
D. >3-fold increases in ALT, AST, and ALP with >2-fold increases in total bilirubin
Answer: A
Explanation and Reference:
Hy’s Law is useful as a prognostic indicator in drug-induced liver injury. It combines serum ALT
>3XULN and serum total bilirubin >2XULN in making a prediction of outcome. C&D 9th pp. 732-733.
Based on current OECD Guidelines, what tester strains of Salmonella typhimurium that revert at GC
base pairs should be used in the Ames Assay?
A. TA 1536, TA 110, TA 1518, TA 85
B. TA 1548, TA 102, TA 1505, TA 92
C. TA 1535, TA 100, TA 1538, TA 98
D. TA 1540, TA 200, TA 104, TA 80
Answer: C
Explanation and Reference:
The correct answer lists the recommended tester strains in which reversion by GC base-pair
substitutions and frameshift mutations in several DNA sequence contexts can be detected and
distinguished. The other answers give wrong numbers for some of the strains. C&D 9th, pp. 520-521
The in vivo micronucleus test is often used in a standard battery of genetic toxicity assays. In this test,
what do the micronuclei actually represent?
A. clumps of ribosomes aggregated around rough endoplasmic reticulum
B. binucleated remnants of germ cells in the intracellular space
C. membrane-bound structures that contain chromosomal fragments or whole chromosomes
D. pyknotic nuclei from a cell with decreased cytoplasmic to nuclear ratios and thickened
micronuclear membrane
Answer: C
Explanation and Reference:
Because the micronuclei represent chromosomal fragments, they are simple indicators of DNA
damage, both clastogenesis and aneuploidy. They are not nuclear fragments or ribosomal clumps.
The micronucleus test is run in lymphocytes or erythrocytes, not germ cells. The test is widely
recognized as one of the most useful and reliable tests for carcinogens that act by causing DNA
damage. The test is part of the OECD guidelines for testing chemical safety. C&D 9th, pp. 525-526.
What assay is most commonly used to assesses the ability of a test material to induce chromosomal
aberrations in vivo?
A. thymidine kinase assay
B. rodent micronucleus test
C. bacterial-Ames assay
D. sister chromatid exchange assay
Answer: B
Explanation and Reference:
The micronucleus test is widely recognized as one of the most useful and reliable tests for
carcinogens that act by causing DNA damage. The test is part of the OECD guidelines for testing
chemical safety. C&D 9th, pp. 525-526.
How, in the Functional Observational Battery, would one evaluate the potential effects of a toxicant
on vision?
A. evaluation of ocular irritancy
B. observing the pupillary response to light
C. scoring the degree of lens opacity
D. evaluation of rod and cone density
Answer: B
Explanation and Reference:
Only two visual responses are tested in the FOB; pupil contraction based on light and approach to the
eye. C&D 9th, p. 888.
What do the Buehler and Maximization assays characterize?
A. minipig respiratory efficiency
B. potential of a product to produce skin irritation
C. ribosomal transcription efficiency
D. delayed-contact hypersensitivity
Answer: D
Explanation and Reference:
The Buehler assay was originally developed to test for moderate and strong contact sensitizers using
guinea pigs (GP), while the GP maximization test was designed to maximize the sensitivity of tests
utilizing GPs. Both techniques are used to assess contact allergies and reactions are typically scored
24-48 hrs after challenge or re-challenge. Hayes 6th, pp. 1447-1448.
During Ames testing for genotoxicity, the test compound is usually treated with a homogenate from
mammalian liver before the addition of the bacteria. What is the basis for this treatment?
A. IARC and FDA regulations specifically require this step, though it can be omitted when using
some of the newer assays
B. enzymes from the mammalian liver are needed to degrade and deactivate possible mutagens in
the test compound before testing
C. many compounds are not mutagenic or carcinogenic, but can be activated into mutagens or
carcinogens by metabolism
D. the mammalian liver homogenate is used to normalize the test samples for protein concentration
in the test
Answer: C
Explanation and Reference:
The liver homogenate (S-9 fraction) are added to simulate liver metabolism to consider transformation
to mutagenic metabolites. C&D 9th, p. 468
What genotoxicity endpoint(s) can be detected by the mouse lymphoma assay?
A. germ cell cytogenetic changes
B. unscheduled DNA synthesis
C. micronuclei degradation
D. forward mutations in mammalian cells
Answer: D
Explanation and Reference:
The mouse lymphoma assay identifies evidence of point mutations, deletions and translocations, and
recombinations. ICH Guideline S2B, Section VI, Note (2) and C&D 9th p. 468.
What primary organ system is affected after consumption of grain treated with mercurial (organic)
fungicides?
A. respiratory
B. hepatic
C. renal
D. nervous
Answer: D
Explanation and Reference:
The nervous system is the target for organic mercury compounds. C&D 8th, p. 999.
What effect is clearly indicative of exposure to nickel?
A. nephropathy
B. Menkes disease
C. contact dermatitis
D. encephalopathy
Answer: C
Explanation and Reference:
Nickel-induced contact dermatitis is found in 10-20% of the population.
Exposure to ethylene glycol monomethyl ether (EGME) and/or one of its metabolites, methoxyacetic
acid (MAA), will induce testicular damage in rats by primarily affecting what cell types?
A. Leydig cell
B. Cowper’s gland
C. Sertoli cell
D. myoepithelial peritubular cell
Answer: C
Explanation and Reference:
Mechanistic studies have shown the Sertoli cell to be affected which disrupts spermatocyte
maturation. C&D 8th, pp. 1078-1079
What organ systems are classic targets of acute and chronic carbon disulfide exposure?
A. upper and lower respiratory system
B. skeletal and cardiac muscle
C. central and peripheral nervous system
D. vascular and lymphatic system
Answer: C
Explanation and Reference:
Exposure to CS2 (dithiocarbonic anhydride) affects a number of organ systems. The effects are
prominent in central and periphernal nervous, system, retina, and as an atherogenic agent. Classic
lesions of CS2 exposure are found in both the peripheral and central nervous systems. There is
evidence that CS2 also modifies low density lipoprotein and enhances arterial fatty de
The Local Lymph Node Assay (LLNA) is an internationally approved method to detect what
pathogenic response?
A. induction of carcinogenesis by a chemical applied to the skin
B. elicitation of sensitivity to a chemical applied to the skin
C. elicitation of carcinogenesis by a chemical applied intratracheally
D. induction of allergic contact dermatitis
Answer: D
Explanation and Reference:
The LLNA is a refinement of the classic GP-MAX and Buehler assys for allergic contact dermatitis.
Whereas the classsic assays measure both induction and elicitation of skin sensitization, the LLNA
only measures induction, resulting in a shorter assay. The LLNA is now the recommended method
for determining allergic contact dermatitis potential of chemicals. Hayes 6th, pp. 1100-1102.
Acetaminophen hepatotoxicity requires what intermediate step?
A. the toxicity does not depend on metabolism of acetaminophen
B. interaction with sodium nitrosulfate
C. binding to cellular macromolecules
D. inhibition by ethanol co-administration
Answer: C
Explanation and Reference:
The toxic metabolite of acetaminophen binds to glutathione; when cellular glutathione is depleted, the
metabolite binds to cellular macromolecules, particularly proteins. C&D, 8th, pp. 651.
Several inhibitors of cyclooxygenase-2 (COX-2) have been removed from the market due to what
potential type of toxicity?
A. hepatic
B. neurologic
C. cardiovascular
D. renal
Answer: C
Explanation and Reference:
These compounds may cause hypertension which elevates the risk of heart attack and stroke. C&D,
8th, pp. 819-824.
What substance is the most effective agent for treating acute mild inorganic mercury intoxication?
A. British Anti-Lewisite (BAL)
B. hydrochlorothiazide
C. intravenous glucose
D. aminophylline
Answer: A
Explanation and Reference:
The chelating agent BAL, also called as dimercaprol, is effective with inorganic poisoning. C&D 8th,
p. 999
Why is beryllium unique among metals?
A. it causes injury in skin and lung through an immune mechanism
B. it is not excreted in the urine following uptake in lymph
C. it cannot be absorbed orally
D. it is readily absorbed through the skin
Answer: A
Explanation and Reference:
Beryllium causes an inflammatory immune reaction. C&D 8th, pp. 989-999
Organic solvents are a group of compounds that have what characteristics?
A. low vapor pressure at room temperature
B. high molecular weight side chains including -OH groups
C. cannot be absorbed across the skin in significant amounts
D. common effects on the central nervous system
Answer: D
Explanation and Reference:
CNS effects are common to solvents. C&D 8th, pp. 1031-1036.
The “Elixir Sulfanilamide” tragedy, resulted in the passage of the Copeland Bill in 1938 due to what
environmental effects?
A. diethylene glycol induced acute kidney failure
B. ethanol induced liver toxicity and blindness
C. diethylene glycol induced acute liver failure
D. polyethylene glycol induced renal failure
Answer: A
Explanation and Reference:
The drug was found to be more soluble in diethylene glycol and sold as that formulation, but
diethylene glycol caused acute renal failure in several patients. C&D 9th, p. 12
Acute poisoning by malathion is recognized by what group of effects?
A. acute renal failure followed by lacrimation and defecation
B. burning and discoloration of the mucous membranes
C. salivation, lacrimation, headache, and dizziness
D. pulmonary fluid accumulation and respiratory failure
Answer: C
Explanation and Reference:
Malathion is an OP with symptoms as described in C&D 8th, p. 941, Table 22-9
For most systemically administered drugs, what measure is used to convert the animal dose to a
human equivalent dose (HED)?
A. mg/m2
B. Cmax
C. AUC
D. mg/kg
Answer: A
Explanation and Reference:
mg/m2 is the recommended conversion, the other values should be adjusted depending on toxicity
observed in animal studies. FDA Guidance (2010) M3(R2), Table 3
Organophosphates and carbamates exhibit which characteristics?
A. they act by a common mechanism, but arise from two distinctively different chemical classes
B. they do not undergo extensive biotransformation in most species
C. their binding to the acetylcholinesterase is irreversible except in rare instances
D. they were first developed as warfare agents during World War I
Answer: A
Explanation and Reference:
Organophosphates and carbamates both inhibit acetylcholinesterase. C&D 8th, pp. 939-947
Based on your knowledge of toxicology, what is the general line of treatment for scombrotoxicosis?
A. induced emesis with apomorphine
B. intramuscular injection of cortisone
C. intravenous injection of sodium nitrite
D. enteral or parenteral administration of antihistamine
Answer: D
Explanation and Reference:
Histidine occurs naturally in many fish, and at temperatures above 60°F on air contact it is converted
to the biogenic amine histamine via the enzyme histidine decarboxylase produced by enteric bacteria.
Histamine is not destroyed by normal cooking temperatures, so even people eating properly cooked
fish can be affected. Hayes 6th, pp. 662-663
What oxidation state of arsenic is considered to be the most toxic?
A. divalent
B. pentavelent
C. trivalent
D. hexavalent
Answer: C
Explanation and Reference:
Trivalent forms of As are more toxic compared to pentavalent forms. C&D, 8th ed., 986-989.
What characteristic clinical sign is associated with industrial exposure to vanadium pentoxide dust?
A. non-fibrotic pneumoconiosis
B. greenish-black discoloration of the tongue
C. glucosuria
D. gastroenteritis, polyneuropathy, and alopecia
Answer: B
Explanation and Reference:
Glucosuria is a common sign of uranium-related renal toxicity; non-fibrotic pneumoconiosis is
commonly assocxiated with chornic exposure to tin; gastroenteritis, polyneuropathy, and alopecia are
classic signs of thallium poisoning. The blue-green discoloration of the tongue is very characteristic
of Vanadium exposure in industrial settings. C&D 8th, pp. 1018-1021.
What is the recommended treatment for methanol intoxication?
A. intravenous hemoperfusion
B. forced diuresis with emetic.
C. inhibition of alcohol dehydrogenase by 4-methylpyrazole (fomepizole)
D. inhibition of aldehyde dehydrogenase by disulfiram
Answer: C
Explanation and Reference:
Metabolic blockade by ethanol or 4-methylpryazole is first line treatment. Sodium bicarbonate by i.v
can by used to correct metabolic acidosis and folate can be used to enhance formate excretion. C&D
8th p. 1073.
What is the basis for the use of ethanol as an antidote for accidental oral methanol poisoning?
A. it binds with methanol and increases urinary excretion
B. it competitively inhibits the metabolism of methanol
C. it increases metabolism of methanol to formaldehyde
D. it chemically alters methanol to formate
Answer: B
Explanation and Reference:
Inhibits alcohol dehydrogenase blocking the formation of formic acid. Folate is also given to enhance
efficiency of formate oxidation. C&D 7th, pp 1012-1014; C&D 8th, p. 1073
What is the most effective treatment for mammalian organophosphate (OP) toxicity?
A. atropine
B. diazepam
C. 2-PAM
D. epinephrine
Answer: A
Explanation and Reference:
As a muscarinic receptor antagonist, atropine prevents the action of accumulating acetylcholine on
cholinergic receptors. The administration of pralidoxime (2-PAM) early after OP exposure can help
prevent acetylcholinesterase aging. Diazepam may be used for relieving anxiety, muscle
fasciculations, and convulsions. C&D 7th, p.891; C&D 8th p. 941.
What is the preferred treatment of cyanide poisoning?
A. sodium nitrite
B. atropine followed by 2-PAM
C. dimercaprol and pralidoxime
D. calcium disodium edetate (EDTA)
Answer: A
Explanation and Reference:
Nitrite converts hemoglobin to methemoglobin which in turn competes effectively for CN with the
mitochondrial cytochrome oxidase complex. Hayes 6th p. 22
In the field of epidemiology, what parameter is defined as the risk difference between exposed and
unexposed groups, divided by the risk in the exposed group?
A. attributable risk
B. relative risk
C. proportional mortality ratio
D. absolute risk
Answer: A
Explanation and Reference:
Absolute risk is more a concept than a calculation and revolves around the question whether a
specific disease among an exposed group is greater than the absolute risk of that same disease in an
unexposed group. Relative risk (RR) is the ratio of incidence rates in two different groups (e.g.,
exposed versus unexposed). The proportional mortality ratio (PMR) is not to be confused with RR or
absolute risk. This is the number of deaths within a population due to a specific disease or cause
divided by the total number of deaths in the population during a time period such as a year. The
correct answer (A) is attributable risk where rate ratios and rate differences are based on exposure
status. The attributable risk gives a better indication of causality than the other indices. Hayes 6th, p
535.
What are the classic clinical features of the anticholinergic toxidrome?
A. mydriasis, hyperalert, increased pulse, increased blood pressure
B. miosis, decreased pulse, altered mental status
C. miosis, decreased level of consciousness, decreased pulse, no change in blood pressure
D. mydriasis, altered mental status, increased pulse, no change in blood pressure
Answer: D
Explanation and Reference:
Anticholinergic syndrome is produced by the inhibition of cholinergic neurotransmission at muscarinic
receptor sites. Signs include ileus, urine retention, tachycardia, hypertension, confusion, fever, dry
skin, mydriasis. A number of plant exposures can produce this syndrome through the action of
natural constituents such as atropine and scopolomine. Hayes 6th, p. 961.
What is the first step in treating a suspected poisoning victim?
A. submission of blood and urine for immediate analysis
B. administration of the antidote
C. prevention of further toxin absorption
D. stabilization of the patient
Answer: D
Explanation and Reference:
First step is almost always stabilization of the patient (breathing, pulse, etc.). C&D 9th, p. 1533
What is a major limitation of epidemiology studies?
A. exposure conditions are unrealistic
B. exposure is not well-defined or controlled
C. effects are measured in humans
D. interactive effects among individual chemicals cannot be measured
Answer: B
Explanation and Reference:
Exposure is often not well defined and controlled in epidemiological studies especially environmental.
C&D 9th, p. 136
Data from standard toxicology studies conducted with pharmaceuticals are evaluated for signs of
immunotoxic potential. According to ICH S8, what is evidence of immunotoxic potential?
A. alterations in immune system organ weights and/or histology
B. decreased incidence of infections
C. hematological changes such as erythrocytopenia/erythrocytosis
D. mild thymic atrophy accompanied by decreased food consumption and a significant decrease in
body weight gain
Answer: A
Explanation and Reference:
Changes in the hematology panel would not suggest mild changes in the immune system; therefore,
it would be a very insensitive high-level index of immunotoxicity. Similarly, mild thymic atrophy could
be caused by many things including stress. In animals showing decreased food consumption and
body weight, thymic atrophy would be a common finding and not indicative of immunotoxicity. Finally
an increased incidence of infections would suggest immunocompromise; however, a decreased
incidence of infections has little meaning in a preclinical safety study. The correct answer (B),
changes in immune system organ weights and histology, would be routinely measured in a preclinical
study and would require further immune system testing. ICH S8 Harmonized Tripartite Guideline
Immunotoxicity Studies for Human Pharmaceuticals S8, 15 September 2005, Section 2.1.1 page 3.
A 16-year-old harvester was brought to the emergency room after working for 2 days in rain-soaked
tobacco fields. He complained of vomiting, weakness, dizziness, headache, and dyspnea. His vital
signs were a heart rate of 120 beats/minute, blood pressure
A. organophosphates
B. pyrethrin
C. nicotine
D. paraquat
Answer: C
Explanation and Reference:
Green tobacco sickness (GTS) is an illness resulting from dermal exposure to dissolved nicotine from
wet tobacco leaves; it is characterized by nausea, vomiting, weakness, and dizziness and sometimes
fluctuations in blood pressure or heart rate Green Leaf Tobacco Sickness. C&D 9th, p. 858
Repeated occupational exposure to toluene diisocyanates are a common cause of what condition?
A. fibrotic lung disease
B. asthma
C. hemangiosarcoma
D. peripheral neuropathy
Answer: B
Explanation and Reference:
Some individuals develop an allergic reaction to toluene diisocyanates following inhalation exposure.
Re-exposure to the chemical can cause severe asthma symptoms that can be immediate or delayed
for an hour or more. However this usually happens in the workplace and the general public is not
expected to be exposed to such levels. Long-term inhalation exposure can also cause lung damage.
C&D 9th, p. 689-690
What prospective epidemiological study design assesses development of disease in a population of
known exposure?
A. cross-sectional
B. case-control
C. cohort
D. cross-over
Answer: C
Explanation and Reference:
Case Control - two source populations; assumption that non-cases are representative of the source
population of cases; Correct Answer: Cohort uses exposed and non-exposed populations; Cross over
- longitudinal study in which subjects receive a sequence of different treatments (or exposures);
Cross-sectional - where only ONE set of observations is collected for every unit in the study, at a
certain point in time, disregarding the length of time of the study as a whole; C&D 9th, pp. 136-137
What is the “prevalence” of a disease?
A. the incidence rate
B. the number of cases at a specified moment of time
C. the rate at which new cases develop
D. the cure rate
Answer: B
Explanation and Reference:
Prevalence is what is observed at a single point in chronological or biological time. Hayes 6th, p. 531
What type of epidemiological study is used to compare disease prevalence or health status between
groups of workers classified according to job titles, work site, or exposure status in present time?
A. case-control
B. cross-sectional
C. retrospective cohort
D. prospective cohort
Answer: B
Explanation and Reference:
Cohort studies are always prospective and report out incidence. Case-control studies are
retrospective and report out fractional percent of disease vs non-disease subjects. Only the crosssectional
study design reports out prevalence- where only ONE set of observations is collected for
every unit in the study, at a certain point in time, disregarding the length of time of the study as a
whole. C&D 8th, p. 131.
An individual has taken an overdose of atropine. What is the appropriate treatment/antidote?
A. methyl-atropine, another competitive acetylcholine antagonist
B. nicotine, a nicotinic antagonist
C. physostigmine, an acetylcholinesterase inhibitor
D. succinylcholine, a nicotine antagonist
Answer: C
Explanation and Reference:
Physostigmine, given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5 to 1.0 mg
in children), rapidly abolishes delirium and coma caused by large doses of atropine. Since
physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and
repeated doses may be required. Artificial respiration with oxygen may be necessary. Ice bags and
alcohol sponges help to reduce fever, especially in children. C&D 9th, p. 1064
What is the most frequently encountered xenobiotic among emergency toxicology cases?
A. ethanol
B. methamphetamine
C. painkillers
D. heroine
Answer: A
Explanation and Reference:
Nearly 88,000 people die annually in the United States as a direct or indirect exposure to alcohol.
C&D 9th, p. 1525
What testicular tumor is a frequently occurring endocrine tumor in rodent chronic
toxicity/carcinogenicity studies (i.e., observed at a background incidence in the F344 rat of 70-90%)?
A. granulosa cell tumor
B. dendritic cell tumor
C. Leydig cell tumor
D. Sertoli cell tumor
Answer: C
Explanation and Reference:
Control F344 rats have an extremely high spontaneous incidence of Leydig cell tumors. Therefore,
these tumors are believed to be irrelevant to men. C&D, 8th ed., pp. 1055-1056.
What is a common observation in rodent models when thyroid hormone homeostasis is disrupted?
A. increased incidence of thyroid tumors
B. disruption in body temperature maintenance
C. reductions in overall animal body weight
D. Due to reserve capacity of the thyroid, hormone disruption does not result in observable toxicity.
Answer: A
Explanation and Reference:
A reduction of thyroid hormone concentrations and increased thyroid-stimulating hormones have
shown to induce neoplasia in the rodent thyroid. C&D 8th, pp. 412-413.
Delayed Type Hypersensitivity is associated with what characteristic?
A. chemical presentation to Langerhans cells
B. absence of inflammation
C. clonal expansion of B cells
D. cell-mediated response
Answer: D
Explanation and Reference:
Delayed Type Hypersensitivity (DTH) is cell, not antibody mediated. C&D 9th, p. 1038-1040
What would produce a level of great concern for the development of human cancer, based on
preclinical laboratory and animal data?
A. toxicity associated tumors
B. not genotoxic
C. a finding of tumor site concordance between species
D. single species effect
Answer: C
Explanation and Reference:
Examples shows a weight of evidence approach between species to extrapolate to humans. C&D 9th,
p. 478
Different cell populations of the mammalian testes exhibit different thresholds of sensitivity to different
toxicants. What region/cell type in the testes is generally considered to be the most sensitive to
chemical insult?
A. rete testis
B. germ cells
C. the seminiferous epithelium
D. Leydig cells
Answer: B
Explanation and Reference:
Germ cells are typically the most sensitive. C&D 8th,pp. 874-878.
Where is inhibin, a regulator of FSH production and a biomarker for male reproductive damage,
secreted/produced from?
A. Leydig cells
B. spermatogonia
C. Sertoli cells
D. epididymides
Answer: C
Explanation and Reference:
Inhibin is produced by Sertoli cells in the seminiferous tubules, not in the spermatogonia or
epididymides. Leydig cells are the sites of testosterone biosynthesis. Hayes 6th, p. 1621.
What is the fate of very water-soluble gases in the respiratory system?
A. trapped by bronchiolar mucus and removed by the mucociliary escalator
B. transported directly to the deep lung and absorbed into the general circulation
C. absorbed into the systemic circulation through the capillaries of the nose
D. transported directly to the deep lung where they react chemically with Type II pneumocytes
Answer: A
Explanation and Reference:
Highly water-soluble gases are filtered through the nasal turbinates and are efficiencly absorpbed
from that site. Such gas species rarely make it to the respiratory sections of lung. C&D 8th, p. 692
What common characteristic is shared by all four types of hypersensitivity responses?
A. involves formation of specific immunoglobulin molecules
B. requires prior exposure to an antigen
C. involves activation of mast cells in respiratory bronchioles
D. are cell-mediated responses that are delayed
Answer: B
Explanation and Reference:
One characteristic common to all four types of hypersensitivity reactions is the necessity of prior
exposure leading to sensitization in order to eliciti a reaction upon subsequent challenge. C&D 9th
edition, page 646
What pair of immune-mediated hypersensitivity reactions to chemicals is the most frequently reported
in humans?
A. Type I and Type III
B. Type IV and Type I
C. Type II and Type IV
D. Type III and Type IV
Answer: B
Explanation and Reference:
Mostly manifested as contact and respiratory sensitization, respectively. C&D 9th, p. 660
Which ocular structure is most often affected following systemic long-term or high dose use of
corticosteroids in humans?
A. cornea
B. lens
C. retina
D. iris
Answer: B
Explanation and Reference:
Long-term systemic use of corticosteriouds is implicated in cataracts. C&D 9th edition, page 880
Exposure of rats to a naphthalene-derived pesticide resulted in a loss of circulating erythrocytes that
was accompanied by reticulocytosis and hemoglobinuria. No pathological changes were observed in
the bone marrow; however, spleens were found to be enla
A. anemia due to iron deficiency
B. mechanical (march) hemoglobinuria
C. aplastic anemia
D. non-immune hemolytic anemia
Answer: D
Explanation and Reference:
The data in this case suggest mature red blood cell destruction, possibly caused by xenobiotic
production of reactive oxygen species (explaining the decreased reduced glutathione). The
reticuloytosis suggests that the bone marrow is intact and producing new red cells, so iron-deficient
and aplastic anemias are ruled out. There is no history of mechanical stress. A chemically induced,
non-immune hemolytic anemia is the most likely diagnosis given the history and clinical data. C&D
9th, p. 602-603
Most inhaled particles with a mean aerodynamic diameter of 1 micron are deposited in what
respiratory region?
A. alveoli
B. nasopharyngeal region
C. bronchioles
D. bifurcations of major bronchi
Answer: A
Explanation and Reference:
Particles of ~1 μm are typically deposited in the alveolar region. C&D 9th, p. 795
What is the primary factor that determines the region of the respiratory tract where a particle or an
aerosol will be deposited?
A. size of the particle
B. chemical composition of the particle
C. particle shape
D. respiratory rate
Answer: A
Explanation and Reference:
The efficiency of particle deposition in various regions of the respiratory tract depends mainly on
particle size. C&D 9th, p. 803
Type III hypersensitivity reactions are mediated by what combination of immunoglobulin or cell type?
A. IgG and antigen
B. IgE and macrophages
C. T lymphocytes and macrophages
D. IgE and mast cells
Answer: A
Explanation and Reference:
Type III Hypersensitivity involve the IgG against soluble antigen in the serum. C&D 9th, p. 647
What ocular structure is the target of chronic, high-dose tamoxifen therapy?
A. cornea
B. lens
C. retina
D. conjunctiva
Answer: C
Explanation and Reference:
Tamoxifen, a nonsteroidal antiestrogenic drug that competes with estrogen for its receptor sites and
used for treatment of metastatic breast carcinoma, causes retinopathy following chronic high-dose
therapy. C&D, 9th ed. p. 892
What toxico-pathological feature characterizes hepatic steatosis?
A. accumulation of smooth endoplasmic reticulum in hepatocytes
B. accumulation of lipids in hepatocytes
C. hepatocyte nuclear lysis
D. retention of bilirubin
Answer: B
Explanation and Reference:
Steatosis or “fatty liver” is the accumulation of lipids, primarily triglycerides, within the hepatocytes.
Hayes, 6th ed., pp. 1447-1448; C&D 9th pp. 727-728.
What toxic food contaminant is a major by-product of cooking at high-temperatures?
A. heterocyclic amine
B. botulinum toxin
C. fumonisin
D. trichothecene
Answer: A
Explanation and Reference:
Heterocyclic amines are formed as a result of high-temperature cooking of foods high in proteins and
carbohydrates. C&D 9th, p1350
The presence of melamine as an adulterant in infant formula and pet food was associated with
mortalities in human infants and pets in the mid-2000s. What was the mechanism of action
underlying melamine-related toxicity?
A. acute hepatic toxicity
B. acute cardiac toxicity
C. blockade of mitochondrial oxidative phosphorylation
D. formation of crystaline precipitates in renal tubules
Answer: D
Explanation and Reference:
Melamine often in combination with cyanuric acid has been associated with renal failure in children
and companion animals. The mechanism of toxicity is crystal formation in the tubules and bladder.
The source of melamine was its illegal addition to increase nitrogen content in order deceive test
inspections for protein content. Torres and Bobst, Toxicological Risk Assessment for Beginners, p.
23.
Ethanol, retinoids, valproic acid, and the angiotensin converting enzyme (ACE) inhibitors share what
common toxicological characteristic?
A. cause liver toxicity
B. have central nervous system effects
C. are human developmental toxicants
D. lower blood pressure
Answer: C
Explanation and Reference:
These are known to cause craniofacial malformations, heart and limb malformations oligohydramnios,
fetal growth retardation, pulmonary hypoplasia, joint contractures, hypocalvaria, neonatal renal
failure, hypotension, and death. C&D 9th, p. 550, 551,
What adverse effect related to low level exposure to lead in blood is of greatest public health concern
?
A. anemia
B. proximal tubular nephropathy in the elderly
C. cognitive delays and behavioral changes in children
D. encephalopathy
Answer: C
Explanation and Reference:
Neurological changes in the developing brain are the most sensitive and greatest concern from lead
exposure. C&D 9th, p 863
John really enjoys grapefruit juice and consumes several large glasses per day. He recently started
taking a new medication and has begun to experience severe muscle aches. Lab tests have
revealed elevated creatine kinase and alanine aminotransferase le
A. acetaminophen
B. atorvastatin
C. naproxen
D. cyclosporine
Answer: B
Explanation and Reference:
Components in grapefruit juice inhibit intestinal CYP3A4 which blocks the metabolism of statins such
as atorvastatin. C&D 9th, p 290-291, 307-310
Why might epidemiological data be considered to be preferable for dose-response modeling in certain
cases?
A. by using biomarkers, the doses associated with effects can be more precisely defined, thereby
avoiding the need for external dose estimation
B. it is possible to model dose-response relationships directly in humans, thereby avoiding concern
for species differences
C. the impact of exposure over a lifetime can be more easily examined than in a multiyear laboratory
animal study
D. the causal relationship between dose and response can be easily established
Answer: B
Explanation and Reference:
Epidemiology studies do monitor dose-response relationships in humans by directly evaluating
human data on exposure and incidence. Confounding factors such as life style, multiple exposures
and robust exposure estimates impact the outcome. C&D 9th, p 136
Two contractors hired by a health club to refinish the racquetball court floors were using a varnish
stripper to remove the old finish. They were found dead on the court after the management requested
they seal the air vents due to patron complaints about
A. myocardial sensitization due to the use of n-hexane
B. narcosis and chemical hypoxia from the use of methylene chloride
C. central nervous system depression from carbon disulfide exposure
D. pulmonary edema from the use of methyl n-butyl ketone
Answer: B
Explanation and Reference:
Metabolism of methylene chloride releases carbon monoxide resulting in carboxyhemoglobin and
tissue hypoxia. C&D 7th, p. 1003
Cutaneous paresthesia is the primary adverse effect from occupational exposure to what pesticide?
A. deltamethrin
B. parathion
C. carbaryl
D. dichlorodiphenyltrichloroethane (DDT)
Answer: A
Explanation and Reference:
Metabolism of methylene chloride releases carbon monoxide resulting in carboxyhemoglobin and
tissue hypoxia. C&D 9th, 1191
Cadmium may accumulate in the kidney without toxic effect for what reason?
A. cadmium decreases the excretion of urinary proteins
B. cadmium binds to metallothionein and forms a metal-protein complex
C. cadmium increases renal tubular absorption of phosphate
D. cadmium produces oliguria
Answer: B
Explanation and Reference:
Cadmium induces metallothionine with subsequestration of cadmium as Cd-MT complex. C&D 9th p.
783`
What primary factor would increase the oral bio-availability of metals from a soil matrix?
A. increased fraction of metals tightly bound to the soil matrix
B. increased ratio of soil lead: arsenic dissolving in gastric acid
C. increased age of the exposed individual
D. increased water solubility profiles of metals in the soil matrix
Answer: D
Explanation and Reference:
This is the primary effect from occupational exposure to pyrethroids such as deltamethrin. C&D 9th,
p. 1073
What is the primary target organ for xylene and ethylbenzene toxicity?
A. central nervous system
B. lungs
C. bone marrow
D. reproductive organs
Answer: A
Explanation and Reference:
These compounds have limited capacity to adversely affect organs other than the CNS. C&D 9th p
1202
What is the mechanism for a polar organic solvent to enter the body via the skin?
A. inhibition of oxidative phosphorylation in the stratum granulosum
B. inhibition of acetyl coenzyme A in melanocytes of the subdermis
C. affects fatty acid synthesis in the dermis
D. disruption of lipids in the stratum corneum thereby increasing the skin’s permeability
Answer: D
Explanation and Reference:
Solvents can (1) remove much of the lipid matrix of the stratum corneum, making holes on artificial
shunts in the penetration barrier; (2) alter keratin configuration to change protein structure; and (3)
function as a swelling agent. Hayes 5th, pp. 692-693, C&D 9th, 9th p. 173
Inhibition of what enzyme is involved in acute toxicity of organophosphate insecticides?
A. carboxylesterase
B. acetylcholinesterase
C. neuropathy target esterase
D. butyrylcholinesterase
Answer: B
Explanation and Reference:
The target of organophosphate and carbamate insecticides is acetylcholinesterase. Both AChE and
NTE may be targets for OPs, but AChE is responsible for the actue effects, and NTE is responsible
for delayed effects (OPIDN) for some OPs. C&D 9th, p. 1064
Paraquat is a herbicide associated with what mechanism of toxicity?
A. alkylating DNA
B. GABA Inhibition
C. free radical formation
D. anticholinesterase inhibition
Answer: C
Explanation and Reference:
Paraquat is associated with free radical formation through its redox potential. DNA alkylation is not a
primary mechanism of pesticides. Organophosphate and carbamate insecticides inhibit acetylcholine
esterases. Type II pyrethroid, cyclodiene, and phenylpyrazole insecticides inhibit GABA receptors.
C&D 9th p. 1085 and Table 22-8
What is the mechanism of toxicity of carbon monoxide?
A. methemoglobinemia
B. inhibition of cytochrome oxidase
C. formation of cyanohemoglobin
D. formation of carboxyhemoglobin
Answer: D
Explanation and Reference:
The toxic action of CO is formation of carboxyhemoglobin preventing oxygenation of the blood.
Cyanide inhibits cytochrome oxidase. Methemoglobin can be induced using sodium nitrite as an
antidote to cyanide poisoning to facilitate the formation of cyanohemoglobin. C&D 9th, p. 1499
What inhaled particles typically deposited in the nasopharyngeal region of an adult human?
A. 2 - 3 μm
B. > 10 μm
C. < 0.5 nm
D. 0.1 - 1.0 μm
Answer: B
Explanation and Reference:
Particles larger than 5 micrometers are generally trapped in the upper airways. (Nasopharyngeal: >10
um; Tracheobronchiolar: 2.5-10 um; Alveoli: <5 um) C&D 9th, p. 795
What type of radiation has the highest linear energy transfer (LET)?
A. alpha particles
B. beta particles
C. gamma rays
D. x-rays
Answer: A
Explanation and Reference:
Alpha particles are characterized by a high energy loss per unit path length and a high ionization
density along the track length, i.e., high LET. X-rays, gamma-rays, and β particles of similar energies
produce sparse ionization tracks and are classified as low-LET radiation. C&D 9th, p. 1258
What elements are essential nutrients?
A. iron, nickel, copper
B. zinc, copper, cobalt
C. vanadium, thallium, manganese
D. copper, beryllium, selenium
Answer: B
Explanation and Reference:
Cobalt, copper, iron, magnesium, manganese, molybdenum, selenium, zinc, and contraversially,
trivalent chromium are essential metals. Nickel, beryllium, thallium, and vanadium are not essential
nutrients. C&D 9th, pp. 1131-1140
How does 4-methylpyrazole inhibit ethylene glycol poisoning?
A. blocks the metabolic activation of ethylene glycol
B. increases glucuronide conjugation of ethylene glycol
C. increases in the glomerular filtration of ethylene glycol
D. blocks the absorption of ethylene glycol
Answer: A
Explanation and Reference:
4-Methylpyrazole (fomepizole) is an alcohol dehydrogenase (ADH) inhibitor which blocks metabolic
bioactivation of ethylene glycol (EG). C&D 9th, p. 1211
What is the mechanism of DDT toxicity?
A. inhibition of GABA receptors
B. inhibition of acetylcholine receptors
C. activation of sodium channels
D. activation of acetylcholinesterase
Answer: C
Explanation and Reference:
DDT and Type I pyrethroids activate sodium channels. Type II pyrethroid, cyclodiene, and
phenylpyrazole insecticides inhibit GABA receptors. Activation of acetylcholine esterase is not a
primary mechanism of pesticides. Organophosphate and carbamate insecticides inhibit acetylcholine
esterases. C&D 9th, p. 1062, Table 22-8;
Piperonyl butoxide inhibits CYP450 and increases the toxicity of which compounds
A. mirex
B. carbamates
C. organophosphates
D. pyrethroids
Answer: D
Explanation and Reference:
Inhibition of CYP450 by piperonyl butoxide increases the toxicity of pyrethroids. C&D 9th, p. 1071
What reaction is responsible for the neurotoxic effects induced by pyrethroid insecticides?
A. activation of chloride channels
B. modification of sodium channel gating
C. inhibition of acetylcholinesterase
D. inhibition of glutamine synthetase
Answer: B
Explanation and Reference:
The principal mode of action of pyrethroids in mammals is the same as in insects: disruption of the
voltage-gated sodium channels. Type II pyrethroids, but not type I compounds, also bind to and inhibit
GABAA-gated chloride channels. Other reported targets for pyrethroids include calcium ATPase and
voltage-gated calcium channels. C&D 9th, p. 1093
What is the mechanism of fluoroacetate/ fluoroacetamide rodenticide toxicity?
A. inhibition of the Kreb’s cycle
B. inhibition of coagulation
C. induction of GI tract necrosis
D. displacement of oxygen from heme
Answer: A
Explanation and Reference:
Fluoroacetate is incorporated into fluoroacetyl-coenzyme A, which condenses with oxaloacetate to
form fluorocitrate, which inhibits mitochondrial aconitase. This results in inhibition of the Krebs cycle,
leading to lowered energy production, reduced oxygen consumption, and reduced cellular
concentration of ATP. Blockage of energy metabolism is believed to account for most signs of toxicity.
C&D 9th, p. 1093
What is the mechanism of ingested zinc phosphide toxicity?
A. phosphoric acid released from hydrolytic reaction of water in the stomach
B. phosphorus released from hydrolytic reaction of water in the stomach
C. phosphine gas formed from hydrolytic reaction of water in the stomach
D. zinc salts released from hydrolytic reaction of water in the stomach
Answer: C
Explanation and Reference:
Phosphine is highly toxic causing widespread cellular damage to the G.I. tract, liver, and kidney. Zinc
would form insoluble salts at this pH without any adverse effects. It is unlikely that any significant
amounts of phosphide would be converted to phosphorus (non-toxic). Phosphoric acid is a FDAapproved
GRAS substance and commonly found in soft drinks. It is essentially non-toxic. C&D 9th, p.
1093
What is the cellular mechanism of hydrogen sulfide toxicity?
A. damage of mitochondrial DNA
B. depletion of ATP reserves
C. inhibition of cytochrome oxidase
D. disruption of cell membranes
Answer: C
Explanation and Reference:
Hydrogen sulfide forms a complex bond with iron in the mitochondrial cytochrome enzymes, thus
preventing cellular respiration. C&D 9th, p. 93, Table 3-5 and p. 601
Fungistatic azole drugs block the synthesis of what critical cell membrane components?
A. cholesterol
B. usnic acid
C. mevalonate
D. ergosterol
Answer: D
Explanation and Reference:
They inhibit the synthesis of ergosterol (the main fungal sterol). C&D 9th, p. 1091; G&G 12th, p. 1576
What is the primary mechanism of action for mercury-induced non-specific cell injury or cell death?
A. cellular mimicry and replacement of divalent zinc in metalloenzymes
B. formation of DNA adducts or DNA-protein crosslinks
C. uncoupling of mitochondrial oxidative phosphorylation
D. high-affinity binding of divalent mercury to sulfhydryl groups of proteins
Answer: D
Explanation and Reference:
Oxidative stress plays a significant role in Hg toxicity. C&D 9th p. 1129
What is the first step in the enzymatic biotransformation of ethylene glycol to the ultimate toxic
metablite oxalic acid?
A. microsomal oxidation
B. alcohol dehydrogenase oxidation
C. microsomal o-dealkylation
D. cytosolic aldehyde oxidase oxidation
Answer: B
Explanation and Reference:
The first step in ethylene glycol metabolism is oxidation via alcohol dehydrogenase to glycolic acid,
which is further oxidized to oxalic acid. C&D 9th p. 1209, Figure 24-11
What is the first critcal step in transforming carbon tetrachloride into a hepatotoxin?
A. formation of trichloromethyl radicals via CYP2E1 metabolism
B. generation of HCl via oxidative dehalogenation
C. generation of aldehydes by alcohol deydrogenase
D. formation of toxic metabolites via glutathione s-transferase
Answer: A
Explanation and Reference:
For CCl4 to be toxic it must be biotransformed by CYP450 enzymes to highly reactive trichloromethyl
radicals that covalently bind to critical cellular components resulting in lipoperoxidation and loss of
membrane integrity. C&D 9th, p 742
What enzyme is involved in organophosphate-induced delayed polyneuropathy?
A. butyrylcholinesterase
B. ATPase
C. neuropathy target esterase
D. acetylcholinesterase
Answer: C
Explanation and Reference:
NPTE causes digital sensorimotor axonopathy. C&D 9th, p. 1066
What is the plant-specific toxicity resulting from glutamine synthetase inhibition by the herbicide
glufosinate?
A. a toxic build up of aldehydes
B. a toxic build up of ammonia
C. a toxic build up of reactive nitrogen species
D. a toxic build up of glutamine
Answer: B
Explanation and Reference:
Because of the enzyme inhibition, plants die of ammonia accumulation and lack of glutamine, both of
which result in inhibiting photosynthesis and respiration. Mammals have other enzyme systems that
compensate for the effects on glutamine synthetase, so it is relatively non-toxic. High exposure levels,
however, may affect brain and cardiovascular function in humans. C&D 9th, p. 1088
What is the mechanism of pyrethroid toxicity?
A. activation of a a2-adrenergic receptors
B. interference of hormone metabolism
C. disruption of voltage-gated sodium channels
D. inhibition of acetylcholinesterase (AChE)
Answer: C
Explanation and Reference:
Pyrethroids act through disruption of sodium channels. C&D 9th, p. 1072
How do coumarin derivative rodenticides antagonize the synthesis of clotting factors II, VII, IX and X?
A. inhibition of Vitamin K epoxide reductase
B. inhibition of Vitamin D reductase
C. inhibition of Vitamin K epoxide carboxylase
D. inhibition of Vitamin D epoxide reductase
Answer: A
Explanation and Reference:
Coumarins antagonize the action of vitamin K in the synthesis of clotting factors (factors II, VII, IX,
and X). Their specific mechanism involves inhibition of the enzyme vitamin K epoxide reductase,
which regenerates reduced vitamin K necessary for sustained carboxylation and synthesis of relevant
clotting factors. C&D 9th, p. 1092
What chemical asphyxiant forms carboxyhemoglobin and prevents oxygenation of blood?
A. carbon monoxide
B. natural gas
C. kerosene
D. carbon disulfide
Answer: A
Explanation and Reference:
Carbon monoxide has a high affinity for hemoglobin forming carboxyhemoglobin and producing tissue
hypoxia by blocking the reversible binding of oxygen to hemoglobin. Natural gas (methane) is an
asphyxiant because it displaces oxygen from the atmosphere decreasing the percentage of oxygen
available for respiration. Kerosene (jet fuel) is not an asphyxiant and does not form
carboxyhemoglobin. It’s toxicity is most associated with ingestion and aspiration pneumonia.
Similarly, carbon disulfide is not an asphyxiant, with both acute and chronic exposures associated
with nervous and cardiovascular system lesions. C&D 9th pp. 1499-1500, p. 1556 Table 34-2
Oligomycin, cyhexatin, DDT, and chlordecone interfere with mitochondrial ATP synthesis by what
mechanism?
A. inhibition of ADP phosphorylation by acting on ATP synthase
B. inhibition of electron transport complex I (NADH-coenzyme Q reductase)
C. inhibition of oxygen delivery to the electron transport chain
D. inhibition of transcription of key mitochondrial proteins
Answer: A
Explanation and Reference:
These four compounds are classic inhibitors of ATP synthase (A). Inhibitors of the electron transport
chain include rotenone, paraquat, cyanide, and antimycin-A. Classic inhibitors of oxygen delivery to
the electron transport chain include those compounds that would affect the respiratory system,
including gas exchange, and the ability of hemoglobin to carry oxygen. Antiviral drugs and antibiotics
have been associated with impaired transcription of key mitochondrial proteins. C&D 9th, p. 93 Table
3-5
Small insoluble particles that reach the lower respiratory tract (alveolar region) will be cleared
predominantly by what mechanism?
A. diffusion into the blood
B. mucociliary escalator
C. macrophage phagocytosis
D. dissolution in lung fluid
Answer: C
Explanation and Reference:
Deposition of small soluble particles as far as the terminal bronchioles would be cleared by the
mucocilarily escalator. Insoluble particles deposited into the terminal airways and alveoli occurs
below the mucocilarily apparatus would be cleared by alveolar macrophages. Dissolution in lung fluid
is not a clearance mechanism. Insoluble particles would not be expected to cross the alveolar lining
into the blood. C&D 9th p. 808
What liver enzyme defect causes some individuals within ethnic populations, such as Asians and
Native Americans, to have difficulty metabolizing alcohol?
A. CYP1A2
B. alcohol dehydrogenase
C. acetaldehyde dehydrogenase
D. CYP2E1
Answer: C
Explanation and Reference:
Inactive allele for ALDH results in acetaldehyde-induced flushing, tachycardia, nausea, vomiting and
hyperventilation. C&D 9th p. 244-246
By what mechanism do phenobarbital and the peroxisomal proliferator nafenopin cause cancer?
A. hypomethylation of exon regions of growth factor genes
B. inhibition of apoptosis promoting clonal expansion
C. inhibition of DNA replication
D. hypermethylation of promoter regions of DNA
Answer: B
Explanation and Reference:
Apoptosis or controlled cell death is one of the mechanisms by which cells prevent the clonal
expansion of mutated precancerous cells. Both phenobarbital and nafenopin inhibit apoptosis of
initiated cells thereby acting as promoters. Promotors are also referred to as epigenetic carcinogens.
C&D 8th p. 115-116, Fig 3-34
What is the mechanism of thalidomide teratogenicity?
A. cytotoxicity to osteoblasts
B. proliferation of hematopoietic stem cells
C. inhibition of angiogenesis
D. stimulation of autoimmunity
Answer: C
Explanation and Reference:
Interferes with the expression of genes responsible for blood vessel formation, i.e. angiogenesis.
C&D 9th pp. 27, 81, 549
What is the most abundant hepatic cytochrome P450 sub-family in humans?
A. CYP2A
B. CYP2B
C. CYP3A4
D. CYP1A
Answer: C
Explanation and Reference:
CYP3A4 is abundantly expressed in both small intestine and liver and biotransforms many drugs,
herbals and food constituents. C&D 9th p. 288 Table 6-16
How do thiocyanate and perchlorate affect the thyroid?
A. inhibition of thyroid peroxidase
B. inhibition of iodide transport
C. inhibition of thyroid hormone secretion
D. stimulation of the sodium-iodide symporter
Answer: B
Explanation and Reference:
Perchlorate competitively blocks iodide from entering the thyroid by an effect on the Na+/I- symporter
thus preventing the further synthesis of thyroid hormone. C&D 9th, pp. 992, 1339
How is benzene detoxified in first phase metabolic reactions?
A. electrophilic regions of the molecular are conjugated with glutathione
B. mixed disulfides are formed with protein thiols
C. a functional group such as hydroxyl or carboxyl is introduced into the molecule
D. nucleophiles are formed and conjugated by sulfation
Answer: C
Explanation and Reference:
Phase I biotransformation reactions are typically hydrolysis, oxidation or reduction reactions and
prepare the substrate for conjugation in Phase II biotransformation reactions. C&D 9th, p. 73
What is the most effective treatment for protecting against systemic effects from hydrogen fluoride
(HF) burns?
A. sodium nitrite
B. potassium gluconate
C. calcium gluconate
D. sodium gluconate
Answer: C
Explanation and Reference:
Treatment of hydrogen fluoride (HF) burns commonly includes calcium-containing topical
medications. C&D 8th, p. 845, Table 19-2
What is the biochemical mechanism underlying lethality of ricin ?
A. damage to cellular DNA, specifically it causes non-repairable double strand breaks in the nuclear
DNA
B. stimulation of the host immune response, specifically activation of T-lymphocytes releasing proinflammatory
cytokines
C. blockage of ribosomal protein synthesis, specifically inhibition of the 28s rRNA of the ribosome
D. altered neurotransmitter release, specifically inhibition of release of acetylcholine from nerve
terminals
Answer: C
Explanation and Reference:
Ricin is an abundant protein component of Ricinus communis seeds (castor beans) that is exquisitely
toxic to mammalian cells. It consists of an enzymic polypeptide that catalyzes the N-glycosidic
cleavage of a specific adenine residue from 28S ribosomal RNA, joined by a single disulfide bond to a
galactose (cell)-binding lectin. The enzymatic activity renders ribosomes containing depurinated 28S
RNA incapable of protein synthesis. C&D 9th, p. 1280
The in vitro hERG assay is frequently used to evaluate the potential to cause QTc prolongation by
measuring what endpoint?
A. inhibition of sodium channels
B. inhibition of calcium channels
C. inhibition of potassium channels
D. inhibition of chloride channels
Answer: C
Explanation and Reference:
Almost all drugs that have been associated with QT prolongation block the rapid component of the
delayed rectifier potassium channel (IKR), which is coded by the human ether-a-go-go related gene
(hERG) . Blocking the IKR channel results in prolonging the action potential which appears as
lengthening of the QT on the ECG. This delayed ventricular repolarization leads to early after
depolarizations, which can result in just focal activity or re-entrant pathways, and thence TdP. ICH
Harmonised Tripartite Guideline S7B, May 12, 2005, pp. 2, 4
http://www.fda.gov/RegulatoryInformation/Guidances/ucm129121.htm
What anatomic or physiologic features limits access of some chemicals to the brain?
A. low blood flow to the brain compared to other tissues
B. higher concentration of phospholipids in brain tissue
C. presence of ATP-dependent efflux transporters in brain capillary endothelial cells
D. higher protein concentration in the interstitial tissue of the brain relative to other body fluids
Answer: C
Explanation and Reference:
Blood flow to the brain is greater than most other tissues. Carrier-mediated efflux transport enables
molecules with low lipid solubility to traverse the blood—brain barrier. The protein concentration in the
interstitial tissue of the brain relative to other body fluids is reduced. There are low levels of xenobiotic
metabolizing enzymes in the brain tissue. The higher concentration of phospholipids in brain tissue
limits the entrance to very lipophilic compounds The development of the cerebral microvasculature
and the morphological changes plus developmental changes in the endothelial cell carrier transport
systems affects brain uptake of substrates that may be substantially higher in neonates relative to
adults. C&D 9th, p. 840
An organic weak acid with pKa of about 4 is swallowed. What is the likelihood of absorption via
passive diffusion from the stomach (pH about 2) into the blood (pH about 7)?
A. passive diffusion cannot occur with substances capable of ionization; it would have to be
absorbed by a specialized ion transport mechanism
B. an acid cannot be absorbed directly from the stomach; it would have to pass into the small
intestine first
C. absorption will be favored because the acid will be largely non-ionized and diffusible in the
stomach, and largely ionized, non-diffusible and ion-trapped in the blood
D. absorption will not be favored, because the acid will be largely ionized (nondiffusible) and iontrapped
in the stomach and largely non-ionized (diffusible) in the blood
Answer: C
Explanation and Reference:
Organic weak acids are exceptions to diffusion. At pKa, 50% of a weak acid/base is polar
(cationic/anionic) and 50% is non-polar. Using the Henderson-Hasselbalch equation, weak acids are
greater than 50% non-polar in the presnece of a strong acid. The lower the pH, the more non-polar
the weak acid becomes. Therefore, at pH 2 the weak acid will be non-polar and absorbed. At pH 7
the weak acid will be polar and not readily absorbed. C&D 9th, p. 162 Figure 5-4
What is the cause of Heinz body formation?
A. irreversible denaturing of hemoglobin
B. an increased number of heme groups per cell
C. impairment of hemolysis
D. reduction of methemoglobin by methemoglobin reductase
Answer: A
Explanation and Reference:
Heinz bodies are formed by damage to the hemoglobin component molecules, usually through
oxidant damage, or from an inherited mutation (i.e. change of an internal amino acid residue). As a
result, an electron from the hemoglobin is transferred to an oxygen molecule, which creates a
reactive oxygen species (ROS) that can cause severe cell damage leading to premature cell lysis.
Damaged cells are cleared by macrophages in the spleen, where the precipitate and damaged
membrane are removed, leading to characteristic “bite cells”. The denaturing process is irreversible
and the continual elimination of damaged cells leads to Heinz body anemia. Hayes 6th, p. 1319
The pathway in both humans and non-human primates for the metabolism of methanol to
formaldehyde is mediated by what enzyme?
A. hydrogen peroxide catalase
B. formaldehyde dehydrogenase
C. formyl-tetrahydrofolate dehydrogenase
D. alcohol dehydrogenase
Answer: D
Explanation and Reference:
In nonprimates, methanol is oxidized by the catalase-peroxidase system, whereas in primates (Nonhuman
and human), the alcohol dehydrogenase system takes the main role in methanol oxidation.
C&D 9th, p. 1207
What is a cofactor for human cytochrome P450-mediated xenobiotic transformation reactions?
A. glutathione
B. NAD+ (nicotinamide adenine dinucleotide, oxidized)
C. NADPH (nicotinamide adenine dinucleotide phosphate, reduced)
D. UDP (uridine diphosphate)-glucuronic acid
Answer: C
Explanation and Reference:
Protons (H+) are usually delivered from the cofactor NADH or NADPH through specific amino acids in
the CYP enzyme, which relay the protons to the active site, where they are essential for a reductive
splitting of the oxygen so a single atom can be added to the substrate. C&D 9th, p. 272-274; 1442.
Among the cytochrome P450 (CYP) isoforms, which is the most abundantly expressed and involved
in the metabolism of about 50% of all clinically used drugs?
A. 3A4
B. 2D6
C. 1A2
D. 2C19
Answer: A
Explanation and Reference:
Cytochrome P450 3A4 (abbreviated CYP3A4) is an important enzyme in the body, mainly found in
the liver and in the intestine. Its purpose is to oxidize small foreign organic molecules (xenobiotics),
such as toxins or drugs, so that they can be removed from the body. C&D 9th, p. 307
Through what actions do both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated
biphenyls (PCBs) function as environmental endocrine disrupters?
A. retinoid agonists
B. estrogen antagonists
C. Ah receptor agonists
D. androgen agonists
Answer: C
Explanation and Reference:
The common mechanistic pathway for both TCDD and PCBs with regard to endocrine disruption is
binding to the aryl hydrocarbon receptor (AHR). The AHR is a cytosolic nuclear transcription factor
expressed in many tissues. Binding of xenobiotics to the AHR can affect many normal functions
including the immune system and in utero development. See Endocrine Disruptor Screening
Program at EPA [http://www.epa.gov/endo/] C&D 8th, p. 884; C&D 9th, pp. 318-320, 1438-1440.
To what is the difference in sensitivity of the human fetus to carbon monoxide (CO) compared to that
of adults attributed?
A. to the chemical asphyxiant properties of CO
B. to the shorter elimination time of CO from the fetus compared to adults
C. to the higher fetal COHb concentration compared to maternal COHb at the same CO
concentration
D. to the higher tissue oxygenation concentration in the fetus at identical carboxyhemoglobin (COHb)
levels
Answer: C
Explanation and Reference:
Fetal hemoglobin, or foetal haemoglobin, (also hemoglobin F, HbF, or α2γ2) is the main oxygen
transport protein in the human fetus during the last seven months of development in the uterus and
persists in the newborn until roughly 6 months old. Functionally, fetal hemoglobin differs most from
adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the
developing fetus better access to oxygen from the mother’s bloodstream. This would predispose it to
CO poisoning. C&D 9th, p. 1499-1500
The accumulation of cyclic GMP in the corpus cavernosum is enhanced by phosphodiesterase 5
(PDE5) inhibitors such as Viagra. What molecular mechanism of action is responsible for hypotension
induced in men taking Viagra for erectile dysfunction?
A. the formation and the accumulation of cyclic GMP are stimulated by NO and enhanced by the
PDE5 inhibitor, respectively, leading to contraction of vascular smooth muscles
B. the formation and the accumulation of cyclic GMP are stimulated by NO and enhanced by the
PDE5 inhibitor, respectively, leading to relaxation of vascular smooth muscles
C. the formation and the accumulation of cyclic GMP are inhibited by NO and by the PDE5 inhibitor,
respectively, leading to relaxation of vascular smooth muscles
D. the formation and the accumulation of cyclic GMP are inhibited by NO and by the PDE5 inhibitor,
respectively, leading to contraction of vascular smooth muscles
Answer: B
Explanation and Reference:
By blocking the degradation of cGMP, Viagra (sildenafil), as a PDE5 inhibitor, maintains and
increases the vasodilatory signal to the corpus cavernosum allowing and enhancing erection. It is
also a non-specific inhibitor of PDE3. When given alone to men with coronary artery disease, Viagra
can cause a 10% decrease in blood pressure; however, an interaction with organic nitrates can result
in dangerous hypotension. C&D 9th p. 937 and G&G 11th, p. 829-830.
Thiouracil and other goitrogenic compounds produce follicular cell adenomas in rats through what
mechanism?
A. decreasing the secretion of pituitary thyroid stimulating hormone (TSH)
B. receptor-mediated stimulation of thyroid gland by TSH
C. stimulation of the conversion of T4 to T3
D. inhibition of thyroid peroxidase- catalyzed oxidation of iodine (I2) to iodide (I-)
Answer: B
Explanation and Reference:
Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct
effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis and secretion of
thyroid hormones. This includes blockage of organic binding of iodine and coupling of iodothyronines
to form thyroxine (T4) and triiodothyronine (T3) (e.g. sulfonamides, thiourea, methimazole, and
aminotriazole, amongst others). This lowers circulating T3 levels which results in a compensatory
increased secretion of thyroid stimulating hormone (TSH), follicular cell hypertrophy and hyperplasia,
and an increased incidence of follicular cell tumors in 2-year or lifetime studies in rats. C&D 9th, p.
327
What is likely to precipitate a severe hypertensive crisis in a patient taking a monoamine oxidase
inhibitor?
A. grapefruit juice (CYP3A-inhibiting flavones)
B. tyramine-containing foods (sympathomimetic)
C. amitriptyline (tricyclic antidepressant)
D. hydroxocobalamine (vitamin B12 precursor)
Answer: B
Explanation and Reference:
A hypertensive crisis can result from ingestion of tyramine-rich foods in conjunction with monoamine
oxidase inhibitors (MAOIs). C&D 9th, p. 945
What is the underlying mechanism of paraquat lung toxicity?
A. increase in mRNA coding for fibronectin and procollagen preceded by release of cytokines such
as TGF-b and TNF
B. remodeling of the vascular bed with hyperplasia of capillary endothelial cells
C. oxidation of cellular NADPH and eventual depletion of the NADPH content of pulmonary cells
D. degradation of pulmonary surfactant causing accumulation of toxic substances in the pulmonary
phagocytic cells
Answer: C
Explanation and Reference:
Produces a superoxide radical while reducing NADPH + H+ to NADP in pulmonary cells. C&D 9th, p.
1084-1085
What is the mechanism of toxicity of the rodenticide fluoroacetate?
A. metabolism to fluorocitrate and inhibition of aconitase
B. inhibition of mitochondrial ATPase
C. obstruction of renal tubules by precipitation as calcium fluroacetate
D. release of fluoride with subsequent inhibition of water reabsorption by the kidney
Answer: A
Explanation and Reference:
Fluoroacetate is similar to acetate, which has a pivotal role in cellular metabolism. Fluoroacetate
disrupts the citric acid cycle (also known as the Krebs cycle) by combining with coenzyme A to form
fluoroacetyl CoA, which reacts with citrate synthase to produce fluorocitrate which binds very tightly to
aconitase, thereby halting the citric acid cycle. This inhibition results in an accumulation of citrate in
the blood. Citrate and fluorocitrate are allosteric inhibitors of phosphofructokinase-1 (PFK-1), a key
enzyme in the breakdown of sugars. As PFK-1 is inhibited cells are no longer able to metabolize
carbohydrates, depriving them of energy. C&D 9th, p. 92, 857
At what site in DNA is the most abundant alkyl adducts produced by alkylating agents, a site that has
the highest negative electrostatic potential?
A. N7 position of guanine
B. N1 position of adenosine
C. N3 position of cytosine
D. O6 position of thymidine
Answer: A
Explanation and Reference:
An important and abundant source of nucleophiles is contained not only in the DNA bases, but also in
the phosphodiester backbone. Although carcinogen–DNA adducts may be formed at all sites in DNA,
the most common sites of alkylation include the N7 of guanine, the N3 of adenine, the N1 of adenine,
the N3 of guanine, and the O6 of guanine . As the most nucleophilic site in DNA, the guanine N7
atom is a major site of adduction by a large number of alkylating mutagens and carcinogens. Aflatoxin
B1, a powerful mutagen, is believed to act through its reaction with this DNA site. C&D 9th, p. 506
Why is the adrenal cortex predisposed to the toxic effects of many hydrophobic xenobiotic chemicals?
A. a lack of cytochrome P450 enzymes
B. pituitary hormone actions
C. bioactivation of long chain aliphatic compounds
D. large stores of lipids
Answer: D
Explanation and Reference:
Adrenal lipophilic steroid hormones are so hydrophobic they must be bound to serum lipids to be
transported. The adrenal cortex is predisposed to the toxic effects of xenobiotic chemicals for three
reasons. 1. the adrenocortical cells contain large stores of lipids for steroidogenesis. 2. membranes of
the adrenocortical cells contain high levels of unsaturated fatty acids that are susceptible to the
generation of reactive species such as free radicals via lipid peroxidation. 3. adrenocortical cells
express enzymes involved in steroidogenesis, including those of the cytochrome P450 (CYP) family,
which are capable of metabolizing xenobiotic chemicals to reactive toxic species. Thus the adrenals
are particularly sensitive to hydrophobic xenobiotics. C&D 9th, pp. 977, 981
What is a recognized mechanism of toxicity for endotoxins?
A. release of inflammatory mediators from Kupffer cells
B. covalent binding to DNA
C. activation of Ito cells
D. inhibition of mitochondrial oxidative phosphorylation
Answer: A
Explanation and Reference:
Kupffer cells are a type of phagocytic cell that forms the lining of the sinusoids of the liver and can
react to endotoxins (bacterial toxins such as lipopolysaccharides) exacerbating their influence in
manifesting toxicity through the release of reactive oxygen and pro-inflammatory cytokines (i.e., TNFalpha,
IL-1B, IL-6, IL-10). C&D 9th, p. 729 Figure 13-9, 731
What features characterize apoptosis?
A. nuclear chromatin patterns become predominantly euchromatic
B. cytoplasmic shrinkage and nuclear fragmentation
C. intracellular organelles swell and disintegrate with membrane lysis
D. inflammatory mediators respond to cell debris in the extracellular matrix
Answer: B
Explanation and Reference:
Characteristic signs of apoptosis include the shrinking of the cell with fragmentation and condensation
of both nuclear and cytoplasmic materials. The cell then breaks into membrane-bound fragments that
are phagocytized. Chromatin condensation is not a feature of apoptosis and neither is the swelling of
intracellular organelles. Apoptosis is the opposite of necrosis and does not initiate an inflammatory
response. Apoptosis is distinct from necrosis in that necrosis results from cellular damage whereas
apoptosis is a tightly regulated suicide of the cell. C&D 9th, pp. 97-98.
What cytochrome P450 (CYP) is the most abundant in the normal human liver?
A. CYP2D6
B. CYP3A4
C. CYP2E1
D. CYP1A2
Answer: B
Explanation and Reference:
CYP3A4 Is present in large amounts both in liver and small intestine. This isozyme metabolizes a
wide range of drugs and natural products it is very important in some drug-drug interactions. There
are as many as 60 CYPs in the normal human liver, of which CYP3A4 is one of the most important.
C&D 9th, pp. 307-309.
How is the mechanism of flushing syndrome observed after alcohol consumption in a high percentage
of the Pacific Rim Asian population is explained?
A. decreased aldehyde dehydrogenase activity
B. decreased alcohol dehydrogenase activity
C. immediate hypersensitivity
D. increased CYP2E1 activity
Answer: A
Explanation and Reference:
There are a large number of people of Asia-Pacific origin who have a mutation in the gene coding for
the enzyme aldehyde dehydrogenase. This is a single-nucleotide polymorphism (SNP). The clinical
consequence of this mutation is that ethanol is rapidly metabolized by alcohol dehydrogenase to
acetaldehyde where it accumulates because of the decreased aldehyde dehydrogenase activity. It is
the accumulation of acetaldehyde that causes the characteristic flushing of the face and
extremities.The flushing reaction is the result of an accumulation of acetaldehyde in the skin. C&D
9th, p. 740-741, Figure 13-16
What is the most important mechanism for deposition of ultrafine particles <0.2 microns aerodynamic
diameter in lung alveoli?
A. diffusion
B. inertial impaction
C. sedimentation
D. condensation
Answer: A
Explanation and Reference:
Diffusion is the correct answer as most particles <0.5 um will reach the lower lung and alveoli by this
mechanism. Most particles >10 um will be deposited in the nose and pharyx by impaction. While
sedimentation of fine particles (>5 microns) controls deposition in the smaller bronchi, the
bronchioles, and the alveolar spaces, sedimentation is not a signifcant route of ultrafine particle
deposition at sizes <0.5 um. Condensation is not a mechanism of particle deposition. C&D 9th, p.
795, Figure 15-1; p. 805 Figure 15-7
The ability of metallothionein to bind metallic cations is a function of its high content of what
molecule?
A. methionine
B. cysteine
C. lysine
D. N-acetylcysteine
Answer: B
Explanation and Reference:
Metallothioneins (MTs) include any inducible low molecular weight cytosolic protein with highly
conserved cysteines and numerous cysteinyl thiol groups allowing them to bind to a diverse group of
metals. Hayes 6th, p. 2095; C&D 9th p. 1111-1112.
The cytochrome P-450 monooxygenases are concentrated mainly in what two cell types in the lung?
A. Type 1 and Type 2 epithelial cells
B. Type 1 epithelial and Clara cells
C. Clara and Type 2 epithelial cells
D. Type 1 epithelial and endothelial cells
Answer: C
Explanation and Reference:
The major Phase-1 metabolic activities in the lung are primarily mediated by cytochrome P450
enzymes. The cells with the highest concentrations of P450 in the lung are the Clara cell followed by
the Type 2 pneumocyte. Clara, or Club cells, are old terms for the mucus-producing bronchiolar
secretoglobin cells (BSCs). Type 2 cells, also called great alveolar cells or septal cells, are granular
and generally cuboidal in shape. C&D 9th, p. 801
What is the mechanism of carbon disulfide neurotoxicity?
A. impaired protein synthesis
B. interference with acetylcholine
C. neurofilament cross-linking
D. depolymerization of microtubules
Answer: C
Explanation and Reference:
Carbon disulfide (CS2)-induced peripheral neuropathy results from the reaction of CS2 with protein
amino groups to yield initial adducts (dithiocarbamate derivatives). The adducts decompose to an
electrophile (isothiocyanate), which in turn reacts with protein nucleophiles on neurofilaments to
cause covalent protein cross-linking. Progressive cross-linking of neurofilaments occurs during
neurofilament transport along the axon, and covalently cross-linked masses of neurofilaments are
thought to occlude axonal transport at the nodes of Ranvier, ultimately resulting in axonal swelling
and degeneration Crosslinking reagents, such as carbon disulfide, are molecules that contain two or
more reactive atoms capable of binding primary amines, sulfhydryls or other reactive components of
proteins or nucleic acids. C&D 9th, pp. 1225-1226
Cocaine initially causes euphoria, hyperactivity and talkativeness. What mechanism explains this
effect for cocaine?
A. blocking of potassium channels and the reuptake pump in the parasympathetic nervous system
where acetylcholine is the neurotransmitter
B. blocking the reuptake of dopamine, norepinephrine, and serotonin; as well as release of dopamine
from storage vesicles.
C. inhibition of the release of the neurotransmitter in the synapses of the parasympathetic nervous
system and blocking calcium channels
D. blocking of the reuptake of neurotransmitters in synapses of the parasympathetic nervous system
and opening caclium channels
Answer: B
Explanation and Reference:
Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin; as well as release of
dopamine from storage vesicles. These events are credited with the addictive and euphoric
responses to this drug. C&D, 8th ed., pp. 753.
What is a key characteristic of urticaria?
A. responses are independent of histamine
B. contact urticaria is produced by only a few substances
C. reactions occur through a Type 4 hypersensitivity reaction
D. responses are primarily mediated through mast cells
Answer: D
Explanation and Reference:
Urticaria is a skin reaction following release of histamine from sensitized mast cells. The release of
histamine is triggered by exposure of allergens to IgE antibodies on the mast cell surfaces. This is an
immediate-type hypersensitivity response in contrast to a Type-4 cell-mediated hypersensitivity
reaction. Urticaria is common, produced by many substances. C&D 8th, pp. 852-853; C&D 9th, p.
966.
For non-corrosive agents, what characteristics are likely to have the greatest impact on absorption
through the skin?
A. hydrophobic agents with low molecular weight
B. hydrophobic agents with high molecular weight
C. hydrophilic agents with high molecular weight
D. hydrophilic agents with low molecular weight
Answer: A
Explanation and Reference:
While the skin is generally a very good barrier to xenobiotic exposure, small, hydrophobic molecules
can move easily through the skin into the bloodstream. For certain exposure pathways this can be a
major source of internal dose. C&D 9th, p. 955
What is the term given to the severe, acute dermatologic hypersensitivity reaction to various drugs,
characterized by epidermal sloughing leading to a true medical emergency and lethality in some
cases?
A. toxic epidermal necrolysis
B. Grover’s Disease
C. chondrodermatitis helicis
D. Schamberg’s Disease
Answer: A
Explanation and Reference:
Toxic epidermal necrolysis is a rare but life-threatening skin disease resulting from hypersensitivity
reactions to drugs. The Stevens-Johnson syndrome is a milder form of this disease but can still be
fatal. Recovery from Stevens-Johnson reactions can take months and requires avoidance of the
offending drug and similar chemical analogs for life. C&D 9th, p.969
Why is allyl alcohol primarily associated with periportal (zone 1) hepatocellular necrosis?
A. higher concentration of P450 isozyme for bioactivation to acrylic acid
B. disruption of hepatocellular cytoskeletons by binding to actin filaments
C. higher periportal oxygen concentration for bioactivation to acrolein
D. canalicular cholestasis as a consequence of bioactivation to acrolein
Answer: C
Explanation and Reference:
Allyl alcohol is bioactivated by alcohol dehydrogenase oxidation to acrolein and produces periportal
liver injury. Acrolein is a highly reactive α,β-unsaturated aldehyde. It rapidly binds to and depletes
cellular nucleophiles such as glutathione. Because periportal (zone 1) has the highest concentration
of glutathione and oxygen to oxidize allyl alcohol to acrolein, this is the region of toxicity. C&D 9th, p.
742 Figure 13-8; pp. 721-22
What region of the eye is more susceptible to systemic toxicants?
A. cornea and ciliary body
B. retinal pigment epithelium (RPE) and photoreceptors
C. iris and lens
D. cornea and iris
Answer: B
Explanation and Reference:
More vascularized regions of the eye are more susceptible to systemic toxicants. C&D C&D 9th, p.
884, Figure 17-3; p. 890
What is the main liver cell type that produces extracellular matrix proteins and is central to the
development of fibrosis?
A. stellate cell
B. Kupffer cell
C. endothelial cell
D. hepatocyte
Answer: A
Explanation and Reference:
Stellate cells are located between the hepatocytes and the sinusoids (the sinusoidal space). Thus
they are susceptible to toxicant damage and initiation of fibrosis. These cells express smooth muscle
actin; they are contractile and appear to control local flow of blood in the sinusoids. When activated,
especially during chronic injury to the liver, stellate cells can assume a myofibroblastic phenotype,
synthesizing and secreting collagen and other extracellular matrix proteins and thereby can initiate
liver fibrosis. C&D 9th, p. 723
What is the toxicological consequence of ingestion of large amounts of rhubarb leaves?
A. presence of oils capable of eliciting local irritation to the GI tract
B. high concentration of oxalate in the leaves leading to ethylene-glycol-like nephrotoxicity
C. high concentration of hyaluronidase in the leaves leading to local tissue necrosis
D. presence of cyanogenic peptides
Answer: B
Explanation and Reference:
Rhubarb (Rheum rhaponticum) is one of many plants that cause gastrointestinal irritation following
the release of raphides of oxalates. C&D 9th pp. 1278-1279, Table 26-4.
Indicators of kidney function after toxic damage include blood (serum) urea nitrogen(BUN), serum
creatinine, and urine specific gravity. Renal function can be assessed by what method?
A. comparing serum creatine kinase (CK) with serum creatinine
B. ratios of urine sorbitol dehydrogenase (SDH) or lactate dehydrogenase (LDH)
C. calculating glomerular filtration rate and/or Cystatin C clearance
D. measurement of urine output (volume over time)
Answer: C
Explanation and Reference:
Cystatin C is a protein coded by the CST3 gene and primarily used as a biomarker for kidney
function. C&D 9th, p. 777
Non-steroidal anti-inflammatory drugs (NSAIDs) induce acute renal failure which is reversible and
characterized by decreased renal blood flow, glomerular filtration rate, and oliguria in patients
suffering from hypotension, hypovolemia and/or cardiac insu
A. inhibition of lysosomal hydrolases
B. suppression of prostaglandin synthesis
C. disruption of mitochondrial membranes
D. accumulation in renal tubular fluid
Answer: B
Explanation and Reference:
NSAIDs act through the inhibition of prostaglandin synthesis. When the normal production of
vasodilatory prostaglandins (e.g., PGE2 and PGI2) is inhibited by NSAIDs, vasoconstriction induced
by circulating catecholamines and angiotensin II is unrestricted, resulting in decreased renal blood
flow and ischemia. C&D 9th, p. 785
What is the mechanism by which saccharin causes urinary bladder tumors in rats?
A. formation of DNA-reactive free radical metabolites of saccharin in the acidic environment of the
urine
B. the major urinary metabolite of saccharin causes cross-linking of DNA in bladder epithelial cells
C. DNA mutations in transitional epithelial cells of the bladder
D. precipitation of saccharin crystals in the bladder leading to local irritation and hyperplasia
Answer: D
Explanation and Reference:
Bladder cancer in rats administered saccharin only occurred under conditions where the compound
was at such high concentrations in the urine that it formed a crystalline precipitate. It was determined
that these findings were not relevant to humans at normal dietary intakes and beyond. Even at levels
of excessive dietary consumption, such high concentrations would not be achieved in humans. There
is no evidence that saccharin or its metabolites is mutagenic. C&D 9th, p. 135, Table 4-5.
What is the mode of action by which peroxisome proliferator activated receptor alpha (PPARalpha)
agonists cause tumors in rodent livers?
A. hypertrophy and hyperplasia of hepatocytes
B. increased apoptosis and decreased cell proliferation
C. decreased peroxisomal fatty acid degradation
D. decrease in hydrogen-peroxide-generating catalase in hepatocytes
Answer: A
Explanation and Reference:
Chronic administration of peroxisome proliferating chemicals to rats and mice causes hepatomegaly
and ultimate carcinogenesis through non–DNA-reactive mechanisms. PPARα plays a central role in
lipid metabolism and acts as a transcription factor to modulate gene expression following ligand
activation. This latter effect arises through the heterodimerization of PPARα and RXRα, which results
in binding to response elements (PPREs) and subsequent modulation of target gene transcription.
Following this event is the induction of cell proliferation and suppression of apoptosis. Relevance of
this effect to humans is a matter of controversy. C&D 9th, pp 451-452, Figure 8-17
What can cause follicular cell adenoma formation in the rat thyroid?
A. iodine-catalyzed free radical production
B. secondary induction of thyroperoxidase
C. excessive secretion of TSH
D. retarded metabolism of T3 to T4 in peripheral tissues
Answer: C
Explanation and Reference:
Excessive secretion of TSH can act in a proliferating manner. C&D 9th p. 454
The nucleotide excision repair system is initiated by what type of DNA lesion?
A. removal of bulky lesions from DNA
B. induction of aneuploidy
C. damage to individual DNA bases
D. DNA ligation as an initiating event
Answer: A
Explanation and Reference:
The NER system provides a mechanism to remove bulky lesions from DNA. Basic excision repair
mechanisms would be activated in cases of DNA-based damage. DNA ligation and the induction of
aneuploidy are not triggers for the NER system. C&D 8th, p. 452; C&D 9th p. 508.
The O6-methylguanine DNA methyltransferase repair mechanism is a process that protects cells
against DNA damage caused by what class of compounds?
A. ultraviolet light
B. ionizing radiation
C. alkylating agents
D. free oxygen radicals
Answer: C
Explanation and Reference:
Many anti neoplastic drugs are alkylating agents used to inhibit cell division by tumor tissues. C&D
9th, pp. 442, 510
What is considered an acute response of the lung to injury?
A. emphysema
B. interstitial granulomatosis
C. pulmonary edema
D. fibrosis
Answer: C
Explanation and Reference:
Lung injury due to inhalation of acid gas can result in lethal pulmonary edema within hours. C&D 9th,
pp. 813-814
The delayed neurotoxicity observed after exposure to tri-ortho-cresyl phosphate (TOCP) is best
attributed to what process?
A. inhibition of oxidative phosphorylation
B. a genetic polymorphism in the gene responsible for myelination
C. neurofilament protein crosslinking
D. covalent modification of neuropathy target esterase
Answer: D
Explanation and Reference:
TOCP modifies NTE which initiates degeneration of long axons in the peripheral nervous system.
C&D 9th, p. 851-52
The toxicity profile of an inhaled gas or vapor is determined by its site of pulmonary deposition. As a
general rule, where along the respiratory tract are water-insoluble gases such as nitrogen dioxide,
ozone, and methylene chloride absorbed?
A. they bypass the upper respiratory tract and are absorbed in the deep lung
B. they are completely absorbed in the nasal cavity
C. they are readily absorbed by the mucus covering of the conducting airways
D. they must be combined with particulates to reach the deepest areas of the lung
Answer: A
Explanation and Reference:
There are a number of determinants of where a gas or vapor will be absorbed along the respiratory
tract, but as a general rule, highly water soluble gases/vapors tend to be absorbed in the nasal cavity
whereas insoluble gases tend to deposit and be absorbed deeper in the lung. Other factors include
physico-chemical characteristics of the gas or vapor, such as diffusivity, partition coefficient, and
chemical reactivity. C&D 9th. p. 803; Hayes 6th p. 1414.
What is the mode of action for the neurotoxicity of compounds such as n-hexane and carbon
disulfide?
A. destruction of synaptic neurotransmitters
B. distal axonal swelling and degeneration
C. damage to the myelin sheath disrupting signal transmission
D. damage to dendritic processes in neuromuscular junctions
Answer: B
Explanation and Reference:
Both and-hexane and carbon disulfide cause a clinical polyneuropathy. The mode of action is
damage to peripheral axons characterized by axonal swelling and degeneration. The mechanism of
action at the molecular level is unclear; however, there are several working hypotheses. Hayes 6th,
pp. 698-700; C&D 9th 848-851, Table 16-2.
Botulinum toxin A causes flaccid paralysis of skeletal muscle by what mechanism?
A. blocking the release of acetylcholine from synaptic vesicles by exocytosis through the presynaptic
membrane of the neuromuscular junction
B. acting as a competitive antagonist that blocks the nicotinic acetylcholine receptors on the postsynaptic
membrane of the neuromuscular junction
C. blocking the release of neurotransmitters from synaptic vesicles by exocytosis from inhibitory
neurons that synapse with motor neurons
D. stimulating the release of acetylcholine from synaptic vesicles by exocytosis through the
presynaptic membrane of the neuromuscular junction
Answer: A
Explanation and Reference:
Botulinum toxin interferes with a key enzymatic reaction. It is a zinc protease that hydrolyzes the the
fusion proteins necessary for the exocytosis of acetylcholine, preventing its release, and leading to
paralysis. C&D 9th p. 75.
What is the significance of the “aging” reaction with respect to the acute cholinergic neurotoxicity of
an organophosphorus (OP) compound?
A. it slowly reverses the paralysis caused by delayed neuropathy
B. it renders the inhibited acetylcholinesterase (AChE) intractable to reactivation by therapeutic
oximes, such as 2-pralidoxime methiodide (2-PAM)
C. it accounts for the greater resistance of young animals to cholinergic agents
D. it catalyzes the destruction of excess OP compounds in the blood by butyrylcholinesterase
(BChE)
Answer: B
Explanation and Reference:
The characteristics of the aging process is highly dependent upon the type of organic phosphate
involved. C&D 9th, p. 1064
Kupffer and microglia cells are components of the body’s innate cellular immunity. From what cell
line are these cells terminally differentiated?
A. polymorphonuclear cells
B. natural killer cells
C. monocytes
D. T-lymphocytes
Answer: C
Explanation and Reference:
Kupffer cells and microglia are specialized macrophages residing in the liver and brain, respectively.
They are terminally differentiated monocytes (myeloid lineage). T-lymphocytes, natural killer cells,
and PMNs develop along different pathways from bone marrow stem cells (lymphoid lineage). C&D
9th, pp.637-38
A deficiency of folate or vitamin B12 results in an inhibition of thymidine synthesis. This can lead to
the development of what condition?
A. megaloblastic anemia
B. pure red cell aplasia
C. microcytic anemia
D. methemoglobinemia
Answer: A
Explanation and Reference:
A pure red cell aplasia is uncommon and is related to decrease erythroid production in the bone
marrow, but it is not related to deficiencies of either vitamin B12 or folate. Methemoglobinemia is
caused by agents that oxidize the heme protein; vitamin B12 and folate do not do this. Iron deficiency
is the most common cause of microcytic anemia, not deficiencies in vitamin B12 or folate.
Megaloblastic anemia is the characteristic morphological feature of vitamin B12 and folate deficiency.
C&D 9th, pp. 597-98
Of what importance is alpha-2 microglobulin nephropathy in humans?
A. it accumulates in the mitochondria of proximal tubular cells interfering with cellular respiration
B. it is actively secreted by the S2 segment of proximal tubular cells
C. elevated alpha-2μ-globulin is associated with renal hyperplasia
D. humans are not generally considered to be at risk of alpha-2?-globulin nephropathy
Answer: D
Explanation and Reference:
Alpha-2 microglobulin nephropathy is sex-and species-specific. Humans are not believed to be at risk
because 1) humans do not synthesize alpha-2 microglobulin, 2) humans secrete less proteins than
rats, and 3) low molecular weight proteins in human urine are not related to alpha-2 microglobulin.
C&D 9th, p. 783
What is the most common site of toxicant-induced renal injury?
A. glomerulus
B. connecting tubule
C. proximal tubule
D. loop of Henle
Answer: C
Explanation and Reference:
The proximal tubule is the most metabolically active area of the kidney and often the target of
xenobiotic activity. The glomerulus is the primary site for immune complexes, the loop of
Henle/collecting ducts for fluoride ions, and the medulla/papilla for chronically consumed analgesic
mixtures. C&D 9th, p. 776
What compound causes neurotoxicity by mechanism other than interfering with aerobic metabolism
(hypoxia)?
A. carbon disulfide
B. hydrogen sulfide
C. carbon monoxide
D. hydrogen cyanide
Answer: A
Explanation and Reference:
Carbon disulfide (CS2)-induced peripheral neuropathy results progressive cross-linking of
neurofilaments along the axon. C&D 9th, pp. 1224-1227
In what zone of the liver would you expect to see the most damage from CCl4 intoxication?
A. All Zones
B. Zone I
C. Zone II
D. Zone III
Answer: D
Explanation and Reference:
CYP2E1 is associated with activation of CCl4 to its active metabolite, and the highest concentration
of this P450 is in Zone 3 of the liver adjacent to the terminal hepatic venules. Zones 1 and 2 are not
highly associated with metabolic activation and are more rich in mitochondria. “All zones” is not
correct because CCl4 toxicity has been shown to be zone specific. C&D 9th, pp. 721-22, Figure 13-2
What is the basis for the renal toxicity of metals?
A. binding to carbonyl groups
B. initiation of lipid peroxidation
C. generation of reactive oxygen species
D. binding to sulfhydryl groups
Answer: D
Explanation and Reference:
Metals may bind to sulfhydryl group of proteins important to tissue function and survival. C&D 9th, p.
781
Allelic loss of what gene(s) may result in early age onset of cancers?
A. DNA repair genes
B. oncogenes
C. tumor suppressor genes
D. cell cycle genes
Answer: C
Explanation and Reference:
Tumor suppressor genes are comprised of two alleles. Allelic loss of one or both genes would
decrease tumor suppressing activity. Proto-oncogenes and oncogenes also play a role in cancer
induction; however, it is often through mutations that increase the activity of these genes. C&D 9th,
p. 463, Table 8-17
Alteration of normal microtubules function is the primary toxic effect for what compound?
A. cuprizone
B. carbon disulfide
C. taxol
D. atropine
Answer: C
Explanation and Reference:
Taxol (Paclitaxel) binds to tubules and stabilizes the polymerized form in the presence of calcium, a
condition that typically results in dissociation - can result in axonopathy. Carbon disulfide disrupts
neurofilaments causing axonopathy. Cuprizone acts to demyelinate axons causing axonopathy.
Atropine is an anticholineric agent causing acute neurotoxicity. C&D 9th, pp. 848-849, Table 16-2,
854,
What physiological response is characteristic of xenobiotic-induced Gell and Coombs Type I
immunopathy?
A. IgE binding to mast cells and basophils
B. hapten-carrier complex processed by Th1 cells
C. activation of naive T cells
D. complement-dependent lysis
Answer: A
Explanation and Reference:
Type I Hypersensitivity involves the production of IgE which activate mast cells. C&D 9th, p. 646-649
What is a key contribution of Kupffer cells with respect to hepatic toxicity?
A. drug protein adduct presentation does not produce immune activation
B. release of TNF-alpha contributes to idiosyncratic hepatotoxicity
C. activation is a common mechanism of acute hepatotoxicity of a compound
D. hepatotoxicity is due to direct effects of cytokines on hepatocytes
Answer: B
Explanation and Reference:
Kupffer cells release reactive oxygen and pro-inflammatory cytokines (i.e., TNF alpha, IL-1B, IL-6, IL-
10). TNF alpha has been shown to cause/contribute to hepatotoxicity in patients. C&D 9th, pp. 729,
Table 13-9, 730
What compound is a direct activating carcinogen that does not require metabolic activation to induce
cancer?
A. nitrogen mustard
B. azo dyes
C. aflatoxin
D. aromatic amines
Answer: A
Explanation and Reference:
Direct-acting carcinogens do not require metabolic activation or modification to induce cancer.
Examples include epoxides, imines, alkyl and sulfate esters, and mustard gases. Direct-acting
electrophilic carcinogenic chemicals typically test positive in the Ames test without additional
bioactivation with a liver metabolic fraction. Mustard is a direct acting carcinogen that can directly bind
to DNA. Azo dyes, aflatoxin, and aromatic amines are all indirect-acting genotoxic carcinogens that
require metabolic activation to induce cancer. C&D 9th, p. 440, Table 8-8
In the context of carcinogenesis, what are the correct respective designations for benzo[a]pyrene,
benzo[a]pyrene 7, 8 epoxide, and benzo[a]pyrene 7,8 diol-9, 10-epoxide?
A. procarcinogen, proximate carcinogen, and ultimate carcinogen
B. proximate carcinogen, ultimate carcinogen, and procarcinogen
C. carcinogen, partially detoxified carcinogen, and totally detoxified carcinogen
D. fluorescent carcinogen, phosphorescent carcinogen, and phototoxic carcinogen
Answer: A
Explanation and Reference:
BaP is a procarcinogen until metabolized by CYP1A1 to the oxide (proximate carcinogen), which is
further metabolided by epoxide hydrolase to the diol (proximate carcinogen), then metabolized again
by CYP1A1 to the epoxide (ultimate carcinogen). C&D 9th, p. 441, Table 8-4; p. 447
What is considered evidence of a mutagenic event and not a type of DNA damage?
A. adduct formation
B. intercalation
C. base substitution
D. strand breaks
Answer: C
Explanation and Reference:
Mutations occur from errors in DNA repair or replications. C&D 9th p 441-445
What is the key event of “promotion” in a multistage carcinogenesis model?
A. establishment of a stable, heritable change
B. additional mutagenic changes by chemical agents
C. the selective clonal expansion of initiated cells to produce a neoplastic lesion
D. conversion of benign preneoplastic lesions into neoplasia
Answer: C
Explanation and Reference:
In the multistage carcinogenesis model, initiation is damage to DNA that is stable and heritable and is
the first step in this process. Progression is the final step in this multi-step process whereby a benign
pre-neoplastic lesion becomes an active cancer. The middle step is promotion, and this step is
characterized by a selective clonal expansion of initiated cells to produce a preneoplastic lesion.
Promotion does not involve any additional mutagenic changes, and chemicals characterized as
“promoters” are not mutagenic and generally not able to cause tumors by themselves. They act
through mechanisms that involve changes in gene expresseion that in turn result in sustained cell
number in the target tissue either through cell proliferation and mitogenesis and/or the inhibition of
apoptosis. C&D 9th p 438-439
What is the purpose of including cytochalasin B in the in vitro micronucleus assay?
A. to improve assay sensitivity by increasing cellular proliferation rates
B. to facilitate automated scoring by improving uptake of stains for micronuclei in the treated cells
C. to detect kinetochores and enable distinguishing between micronucleus formation by aneugenic
versus clastogenic mechanisms
D. to block cytokinesis and avoid confusion associated with differences in cell proliferation kinetics
Answer: D
Explanation and Reference:
Cytochalasin B is used to block cytokinesis, inhibiting cell division. This results in binucleated and
multinucleated cells. C&D 9th p 441-445
An increase in abnormal sperm morphology indicates that a toxic agent has affected what cell type or
body compartment?
A. hepatocytes
B. caudal epididymis
C. germ cells
D. systemic circulation
Answer: C
Explanation and Reference:
As a general rule, an increase in abnormal sperm morphology suggests affects on germ cells. Effects
of a toxic agent on the systemic circulation or hepatocytes would not necessarily affect sperm
morphology. The caudal epididymis is a preferred site for sampling for both sperm number and
morphology. Hayes 6th, p. 1616
What toxic agent causes reproductive or developmental toxicity by damaging DNA directly?
A. diethylstilbestrol
B. thalidomide
C. retinoic acid
D. radiation
Answer: D
Explanation and Reference:
Of the listed developmental toxicants, radiation is the only agent that exerts its toxicity by directly
interacting with DNA. C&D, 8th ed., pp. 483-486, Table 10-1.
To what can the majority of maternal toxicity during pregnancy be attributed?
A. alcohol and smoking
B. prescription pharmaceuticals in the first trimester
C. unknown etiologies
D. chemical and other environmental exposures
Answer: C
Explanation and Reference:
Overt maternal toxicity can result from a number of underlying mechanisms, which are typically
unknown. C&D 9th p 563
What event or mechanism describes endocrine disruptors?
A. results in increased sperm counts in humans
B. no effect on reproductive tract organogenesis
C. receptor competition or inhibition of steroidogenesis
D. affects only female reproduction
Answer: C
Explanation and Reference:
Endocrine active chemicals are exogenous chemicals that exert their primary toxic effects via
modification of hormonal responses, at relatively low doses that are not seen at higher doses. Diverse
mechanisms have been proposed to eplain the shape of the nonmonotonic dose-response curves for
endrocrine active chemicasls, including dose-dependent cycotoxicity, cell- and tissue-specific
receptors and cofactors, receptor selectivity and down-regulation, receptor competition, and
endocrine negative feedback loops. C&D 9th p 40