questions from Linked In

Question 1

2,4-D, (2,4-dichlorophenoxy acid) has severe ocular toxicity. What about it predicts this effect?
A. LogP of ~2.8
B. Molecular weight of ~221
C. pKA of ~2.8
D. tPSA of ~46.5

Answer 1

A. LogP of ~2.8

Question 2

Yellowing of the eyes and skin is the result of an overdose of a common medication. What is the symptom called and what is the likely cause?
A. flushing and acetaminophen/paracetamol
B. icterus/jaundice and acetaminophen/paracetamol
C. flushing and niacin
D. icterus/jaundice and niacin

Answer 2

B. icterus/jaundice and acetaminophen/paracetamol

Question 3

ICH S5 R(3) Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals gives guidance on DART studies. How many species are generally recommended for testing of small molecules and if possible, for biopharmaceuticals?
A. One
B. Two
C. Three
D. Four

Answer 3

B. Two

Question 4

OECD 203 Gives guidance on how to perform acute fish toxicity testing. It requires what type of concentration information must be reported (i.e., is compulsory) for the test to be considered valid?
A. Difference between nominal and measured
B. Nominal
C. Measured (analytical)
D. Theoretical

Answer 4

C. Measured (analytical)

Question 5

What would be an example of a chemical (i.e., in chemico) assay as referenced in ICH S10 as something that should be tried before moving on to the next level of testing?
A. Animal is given a test chemical to see if there is a response to a given dose
B. Blood is given a test chemical to see if there is a response to a given dose
C. Chemical is given a test chemical to see if there is a response to a given dose
D. Data about a test chemical is put into a simulation to see if there is a response to a given dose

Answer 5

C. Chemical is given a test chemical to see if there is a response to a given dose

Question 6

There are several different metals used to make fireworks turn colors. Sodium stands out because even very small amounts of it can add a bright yellow color to the fireworks. What else is true about sodium?
A. Sodium channels play a key role in excitatory cells (e.g., myocytes, neurons) and are an important toxicological target in humans and other species
B. Sodium is an essential nutrient, but sodium is so common that hyponatremia (low sodium) has only been reported a couple of times in the medical literature
C. Sodium has such low intrinsic toxicity that hypernatremia (high sodium) has only been reported a couple of times in the medical literature
D. Sodium is damaged in cooking and canning so fresh raw foods tend to be better sources of sodium

Answer 6

A. Sodium channels play a key role in excitatory cells (e.g., myocytes, neurons) and are an important toxicological target in humans and other species

Question 7

I’m already hearing the fireworks although July 4th is an hour away. I grew up when fireworks were banned in North Carolina. Concerns about infection with poisonous bacteria leading to permanent paralysis after injury was part of the reasoning behind the ban and vaccination lessoned the risk of getting poisoned with what toxin(s)?
A. Tetanus toxin
B. Thallium compounds
C. Transmissible Spongiform Encephalopathies (TSE) causing prions
D. Trichlorfon created dichlorvos

Answer 7

A. Tetanus toxin

Question 8

Steatohepatitis can be caused by excessive alcohol consumption but can have other causes. Either way it involves the accumulation of lipids in the liver. The increase in the fat composition of a liver would be best captured under what type of “omics” study?
A. Genomics
B. Metabolomics
C. Proteomics
D. Transcriptomics

Answer 8

B. Metabolomics

Question 9

I ran across this small moth while walking around Barber-Scotia campus. It has many common names, southern flannel moth, puss moth,… but that it is also called the “asp” moth clues you into the fact that it starts out as one of the most venomous (and painful) caterpillars in the United States. What is the recommended (and toxicologically sound treatment) if a person gets the fine venomous hairs of the caterpillar stuck in their skin?
A. Adhesive tape because it attaches to the hairs making them easier to remove
B. British anti-Lewisite (BAL) because it binds to heavy metals
C. Compression because it causes the blood to flow slower
D. Diaper cream because it contains dermal protectants

Answer 9

A. Adhesive tape because it attaches to the hairs making them easier to remove

Question 10

The OECD 203 Fish Acute Toxicity Test provides guidance on how long to allow fish taken from larger pools to adjust to their new environment before testing can begin. What is this period called?
A. Acclimatization
B. Baselining
C. Cohabitating
D. Detention

Answer 10

A. Acclimatization

Question 11

An odor threshold is reported for the stripping agent and preservative benzyl alcohol. C&D 8th Chapter 34 explains how this information is derived. What is this type of study called?
A. Case-control
B. Case report
C. Challenge/clinical exposure
D. Cohort

Answer 11

C. Challenge/clinical exposure

Question 12

Why does the ICH recommend against using mice for certain short-term to medium-term testing?
A. Aging occurs too quickly (i.e., short life span)
B. Blood volume and organ sizes are very small
C. Challenging to breed and maintain
D. Diseases found in wild strains limit reliability of the assays

Answer 12

B. Blood volume and organ sizes are very small

Question 13

C&D Ch. 3 8th describes many different ultimate toxicants and their sources. Oxalic acid forms calcium oxalate which precipitates and damages the kidneys. Where does it come from?
A. Acetaminophen
B. Amygdalin
C. Ethanol
D. Ethylene glycol

Answer 13

D. Ethylene glycol

Question 14

ICH S8 covers drug-induced immunotoxicity studies. What does it say is a generally acceptable study design?
A. Daily dosing for 3 days
B. Daily dosing for 7 days
C. Daily dosing for 28 days
D. Daily dosing for 90 days

Answer 14

C. Daily dosing for 28 days

Question 15

If a NOAEL of 600 is found in a study for a chemical and a toxicologist makes the case that the standard 10-fold intraspecies uncertainty factor applies but that only an uncertainty factor of 5 is needed for interspecies variability using just those uncertainty factor what is the ADI (acceptable daily intake) they propose?
A. 12
B. 60
C. 120
D. 300

Answer 15

A. 12

Question 16

The US FDA has provided guidance VICH GL54 for establishing an Acute Reference Dose (ARfD) for residues of veterinary drugs. What is the primary purpose of these studies and ARfDs?
A. Protecting the environment from harmful veterinary drug levels
B. Protecting the farm animals from harmful veterinary drug levels
C. Protecting the farmers and veterinarians from harmful veterinary drug levels
D. Protecting the food supply and consumers from harmful veterinary drug levels

Answer 16

D. Protecting the food supply and consumers from harmful veterinary drug levels

Question 17

ICH M4 describes the Common Technical Document which since it has largely become electronic is generally referred to as the eCTD. It is structured into five modules. What is true about the first module?
a) Animal (i.e., nonclinical) summary reports are required
b) Basic summary of quality is required
c) Clinical study reports are required
d) Documents specific to each region are required

Answer 17

d) Documents specific to each region are required

Question 18

ICH S10 provides guidance on Phototoxicity testing. It describes both in chemico (e.g., Reactive Oxygen Species (ROS)) and in vitro assays (e.g., 3T3 Neutral Red Uptake). What is generally true about these assays?
a) They have both high false positive and false negative rates and are not very reliable.
b) They have both low false negative and false positive rates and either a positive or negative result is enough to preclude further study.
c) They have low false positive but high false negative rates, so a negative result is reliable, but a positive result is only an indication for follow-up studies.
d) They have low false negative but high false positive rates, so a negative result is reliable, but a positive result is only an indication for follow-up studies.

Answer 18

d) They have low false negative but high false positive rates, so a negative result is reliable, but a positive result is only an indication for follow-up studies.

Question 19

ICH S11 gives guidance on nonclinical testing for the development of pediatric pharmaceuticals. All other things being equal what would make further studies most likely to be needed based on the weight of the following evidence?
a) Adolescents will be treated with a high specificity pharmaceutical for acute use.
b) Babies (i.e., neonates and infants being treated with a low specificity pharmaceutical for chronic use.
c) Chronic use of a high specificity pharmaceutical for adolescents.
d) Duration of use is acute, specificity is low and children 2-11 years of age are the population being treated.

Answer 19

b) Babies (i.e., neonates and infants being treated with a low specificity pharmaceutical for chronic use.

Question 20

What is so critical about a Phase I trial?
A. A large number of patients are being treated.
B. Birth defects are a concern as it generally includes pregnant women and/or women who might get pregnant.
C. Children are typically involved.
D. Dogs, monkeys, mice or rats might have been tested preclinically but Phase I is typically the first time a drug is tried in a person.

Answer 20

D. Dogs, monkeys, mice or rats might have been tested preclinically but Phase I is typically the first time a drug is tried in a person.

Question 21

Chapter 2 C&D 9th describes idiosyncratic reactions. Which of the following reactions while idiopathic (i.e., caused by treatment) had a known cause and was not an unpredictable and/or rare event?
a) An antibody to CD28 is given to six phase I clinical trial participants. Within minutes after their first dose, they all develop multi-organ failure. This toxicity was not seen in rodents and non-human primates had only a minor cytokine release, but the patients suffered from a cytokine storm.
b) Barbituates have primary toxicities involving the CNS like excessive sedation and addiction but rarely some patients on phenobarbital will develop Steven’s Johnson syndrome or toxic epidermal necrolysis where part of the skin on their body starts to slough off in an overactive immune response.
c) Carbamazepine is a generally safe anti-epileptic drug but in rare cases severe toxicity of the liver, blood, skin and/or other organs occur. This is thought to be due to the interaction of reactive metabolites and an immune response.
d) Drug induced liver destruction occurs in a small number of patients using the anesthetic halothane. This is thought to be due to the interaction of reactive metabolites and an immune response.

Answer 21

unknown

Question 22

C&D Chapter 9 9th covers Genetic Toxicology. What do the Ames assays and the Big Blue® mouse and Big Blue® rat assays have in common?
a) Animals are always treated in all of the assays
b) Bacteria are always used in all of the assays
c) Colonies are always checked for color changes in all of the assays
d) DNA is always sequenced in all of the assays

Answer 22

b) Bacteria are always used in all of the assays

Question 23

Biological species are classified from very broad categories such domain (e.g., Archaea, Bacteria, Eukarya) down to very narrow and specific ones such as species (e.g., sapiens, radicans). The same is true for chemical species. ClassyFire is a computer program that can be used to classify a chemical. Often it is the more specific structural groups that are most relevant for specific toxicities (e.g., cholinesterase inhibition). Running chlorpyrifos through ClassyFire comes up with a dozen different classifications. Of the answer below, which is the most specific?
A. Heteroaromatic compounds
B. Hydrocarbon derivatives
C. Organooxygen compounds
D. Thiophosphate triesters

Answer 23

D. Thiophosphate triesters

Question 24

Delta 8 THC has unfortunately followed the footsteps of Delta-9 THC and is now being reported as requiring intubation (i.e., life support) for some small children ingesting large doses packaged in candy form. If a 100 kg adult drinks a single beverage with 25 mg Delta 8 THC and a 10 kg toddler eats candy containing 2,500 mg Delta 8 THC how much higher is the toddler’s dose as compared to the adult’s dose in terms of mg/kg?
A. 10
B. 100
C. 1,000
D. 10,000

Answer 24

C. 1,000

Question 25

Essential nutrients stand out for having U-shaped toxicity dose-response curves. Unlike with most chemicals, the absence of an essential nutrient causes harm to the organism. Phenylalanine is an unusual essential nutrient. As an amino acid it is needed to make proteins but too much phenylalanine can permanently damage the developing brain.

Normally the blood levels of phenylalanine are kept low by the enzyme phenylalanine hydroxylase (PAH) which converts excess phenylalanine to the less toxic amino acid tyrosine. However, people born with mutations in the gene that makes the PAH enzyme less effective can develop dangerously high levels of phenylalanine and the condition phenylketonuria (PKU) without careful management of the amount of phenylalanine in their diet.

For patients at risk of developing PKU how does the lack of a fully functioning PAH enzyme change their phenylalanine dose-response curve as compared to one for a patient with fully functioning PAH?

A. The doses of phenylalanine that start causing toxicity on the left side of the U of the dose-response curve increase
B. The doses of phenylalanine that start causing toxicity on the right side of the U of the dose-response curve increase
C. The doses of phenylalanine that starts causing toxicity on the right side of the U of the dose-response curve decrease
D. The dose response curve flips and now looks like an inverted U

Answer 25

C. The doses of phenylalanine that starts causing toxicity on the right side of the U of the dose-response curve decrease

Question 26

Pregnancy category A is the drug category assigned by the US FDA to pharmaceuticals that are thought to have the least risk towards pregnant women. What type of results are required for this kind of classification?
A. Animal reproduction studies have failed to demonstrate a risk to the fetus
B. Birth defects have been demonstrated in animal or human studies
C. Controlled studies in pregnant women have failed to demonstrate a risk to the fetus in the first trimester.
D. Defects have been demonstrated in investigational or marketing experience or studies in humans.

Answer 26

C. Controlled studies in pregnant women have failed to demonstrate a risk to the fetus in the first trimester.

Question 27

There are three employees who test positive for amphetamine on a drug screen. More sensitive testing confirms the presence of amphetamine and the absence of methamphetamine which confirms employee one’s story that they are only taking the prescription medicine Adderall (Dextroamphetamine/Amphetamine). For employee two both amphetamine and methamphetamine are detected which does not confirm their story that they are only taking the prescription medicine Adderall. With employee three, no amphetamine-like compounds are found. However, metabolites of the antidepressant drug bupropion are found in significant quantities in their urine sample. What do these initial test results represent with respect to amphetamines?
A. One: false positive; Two: true positive; Three: true positive
B. One: true positive; Two: false positive; Three: false positive
C. One: false positive; Two: true positive; Three: false positive
D. One: true positive; Two: true positive; Three: false positive

Answer 27

D. One: true positive; Two: true positive; Three: false positive

Question 28

Which chemicals are associated with peripheral neuropathy that is thought at least partly to be due to their symmetrical structures allowing parts of the neurons to be cross-linked but is definitely associated with axonal swelling.
A. Carbon dioxide and nitrogen gas
B. Carbon disulfide and n-hexane
C. Hydrogen cyanide and hydrogen sulfide gas
D. Lead and mercury

Answer 28

B. Carbon disulfide and n-hexane

Question 29

Which of the following is related specifically to the testing of chemicals (e.g., pesticides, pharmaceuticals) in such a manner as to be fit for regulatory submissions to agencies regulating those products (e.g., USEPA, USFDA)?
A. GAP
B. GDP
C. GMP
D. GLP

Answer 29

D. GLP

Question 30

Contrary to the conspiracy theories, the Moderna and Pfizer mRNA based Omicron variant targeted vaccine boosters were tested in human clinical trials before being approved. What is different about these vaccine studies as compared to a more traditional small molecule that is needing approval?
A. Age doesn’t matter so separate pediatric clinical trials weren’t needed
B. Bioburden testing of the materials used wasn’t necessary as cold kills all organisms
C. Clinical trial size was larger than typical for early phase trials because it’s a preventative measure and more subjects were needed to get sufficient power
D. Developmental toxicity was not a concern so pregnant women were enrolled in large numbers from the very beginning

Answer 30

C. Clinical trial size was larger than typical for early phase trials because it’s a preventative measure and more subjects were needed to get sufficient power