LinkedIn Study Questions

Question 1

How many half-lives are needed to get a drug to washout during a cross-over study design (i.e., get down to <1% of original dose)?
A. 2
B. 5
C. 7
D. 10

Answer 1

C. 7; 7 half lives reduced below 1% (~99.2% reduction). Half-live if a measure of the rapidity of elimination of a chemical once exposure has ended.

Question 2

What method would a researcher use to quantify a volatile chemical in an experimental system (e.g., microsomal metabolism, medical device extractables) or relevant sample (e.g., ambient air, drinking water)?
A. GC-MS Headspace
B. LC/MS Negative mode
C. LC/MS Positive mode
D. TLC

Answer 2

A. GC-MS headspace. This approach is used for gases and volatiles to capture gases/fumes/vapors released from a media into a container’s “headspace” for analysis by GC-MS.

LC/MS positive and negative modes are used for anions/cations found in mixtures (pg 1,512 C&D).

Question 3

The handbook recommends knowing how to select a relevant species for testing. Several species are recommended by the OECD for use in ecotoxicology testing. What do water fleas, earthworms and minnows have in common?
A. They all have vertebrae
B. They are all invertebrates
C. They are all form a critical part at the top of their respective food chains
D. They all form a critical part near the base of their respective food chains

Answer 3

D, They all form a critical part near the base of their respective food chains

Question 4

A researcher wants to test a hypothesis they have about the prevalence of polymorphisms and a particular disease state within a population. What kind of study design makes the most sense?
A. Case
B. Case-control
C. Cohort
D. Cross-sectional

Answer 4

B, Case-Control design

Question 5

Contrary to what many people still believe about about the relative safety of cannabis products, THC overdoses have resulted in intubations in some cases. What is the main factor behind this high level of respiratory depression in these severe overdose cases?

A. Absorption through IV administration dramatically increases the toxicity
B. Brodifacoum contamination affects the cardiovascular system
C. Children around 10 kg (i.e., toddlers) are eating near gram quantities of concentrated edibles
D. Delayed effects due to ingestion causes people used to the almost instant high from inhalation to take too much

Answer 5

C. Children around 10 kg (i.e., toddlers) are eating near gram quantities of concentrated edibles

Question 6

OECD 432 covers in vitro 3T3 NRU phototoxicity testing. What is not a requirement for this type of testing because it has not been demonstrated to be relevant in vivo?

A. Activation capacity should be confirmed using a positive control that requires metabolic activation as part of each test
B. BALB/c 3T3 cell line passage number should be kept below 100 or data must be available to demonstrate they still adhere to quality control standards
C. Chlorpromazine or some other phototoxic positive control should be part of each test
D. Dosimetry of the light should be checked before each test

Answer 6

A. Activation capacity should be confirmed using a positive control that requires metabolic activation as part of each test

Question 7

The OECD has approved the Mammalian Erythrocyte Pig-a Gene Mutation assay. This assay has the advantage of being able to be added to another in vivo study thus reducing the number of animals needed. What type of study is this type of assay addition most suitable for?
A. Acute to subchronic repeated dose toxicity studies
B. Bioequivalence studies
C. Carcinogenicity studies
D. Developmental toxicology studies

Answer 7

A, Acute to subchronic repeated dose toxicity studies

The Pig-a gene mutation assay (hereafter called the Pig-a assay) uses an endogenous mammalian gene, the phosphatidylinositol glycan class A gene (Pig-a), as a reporter of somatic-cell gene mutation. In vivo gene mutation tests, such as the Pig-a assay, are especially relevant for assessing mutagenicity because physiological factors, such as absorption of the test chemical from the site of exposure, distribution of the test chemical throughout the test system via systemic circulation, and in vivo metabolism and DNA repair processes, all contribute to the mutagenic responses. The Pig-a assay can be performed with commonly used strains of rats or mice and the test can be conducted without euthanizing the animals

Question 8

Assuming the same daily doses of both acetaminophen and ethanol, and no more than a five-day use of either what is most likely to cause liver toxicity?

Answer 8

B. Drinking alcohol both before and while taking acetaminophen.

APAP toxicity is primarily observed as centrilobular hepatocellular necrosis. APAP can be metabolized to NAPQI (N-acetyl-p-benzoquinone imine) which forms protein adducts if it is not conjugated to glutathione. Protein adducts in mitochondria are the primary driver of hepatotoxicity.

Question 9

OECD 413 describes conducting subchronic inhalation toxicity studies in rats. How many rats does it recommend per test group?

A. Starting out with 3 female and 3 male rats and if they all survive then testing an additional 7 female and male rats
B. 3 female and 3 male rats
C. 10 female and 10 male rats
D. 50 female and 50 male rats

Answer 9

C, 10 female and 10 male rats

This revised Test Guideline 413 (TG 413) has been designed to fully characterize test article toxicity by the inhalation route following repeated exposure for a period of 90 days, and to provide data for quantitative inhalation risk assessments. It was updated in 2017 to enable the testing and characterization of effects of nanomaterials tested.

Groups of at least 10 male and 10 female rodents are exposed 6 hours per day for 90 days to a) the test chemical at three or more concentration levels, b) filtered air (negative control), and/or c) the vehicle (vehicle control). Animals are generally exposed 5 days per week but exposure for 7 days per week is also allowed. Males and females are always tested, but they may be exposed at different concentration levels if it is known that one sex is more susceptible to a given test chemical. The results of the study include measurement and daily and detailed observations (hematology and clinical chemistry), as well as ophthalmology, gross pathology, organ weights, and histopathology. This Test Guideline allows the flexibility to include satellite (reversibility) groups, interim sacrifices, bronchoalveolar lavage (BAL), lung burden (LB) for particles, neurologic tests, and additional clinical pathology and histopathological evaluations in order to better characterize the toxicity of a test chemical.

Question 10

12. OECD 413 describes how to conduct inhalation toxicity testing in rats. How are the test animals divided with respect to bronchiolar lavage and histopathology?

A. So that an equal number of females and males get both
B. They are randomly divided into two equal sized groups
C. A crossover study design is used so that each rat gets both just at different times
D. Each rat gets both as the lungs are divided during necropsy

Answer 10

D, Each rat gets both as the lungs are divided during necropsy.

The right lung is used for histopathology, and the left lung is analyzed for bronchoalveolar lavage fluid (BALF).

Question 11

OECD 413 Covers Subchronic inhalation toxicity study design. What is an accurate statement about how the test is conducted?

A. Animals are exposed to the test chemical for 24 hours a day
B. Bronchoalveolar lavage is performed after lung histopathology
C. Concentration levels are assigned to unique animal groups
D. Dose range finding studies are not applicable for inhaled chemicals

Answer 11

C, Concentration levels are assigned to unique animal groups

Daily exposures are for a minimum of 6-hours per day, 5-7 days per week for 90 days. 24 hours/day is excessive and impractical for OECD 413. Bronchoalveolar lavage and histopathology are conducted on separate lungs, left and right respectively. Dose range finders are conducted for inhalation studies with a maximum of 5 animals per sex per treatment group.

Question 12

Which of the following answers is the longest study type performed in rats as part of pharmaceutical development?
A. Acute
B. Biomarker
C. Carcinogenicity
D. Developmental

Answer 12

C, Carcinogenicity

Carcinogenicity studies tend to be 18 months to 2.5 years depending on the species (mice versus rats).

There are 10 key characteristics of carcinogens.

Question 13

Young children drink more than adults. But they are also more susceptible to water-based contaminants than adults. What chemical is known for causing blue baby syndrome due to it’s ability to cause methemoglobinemia?
A. Arsenic in drinking water
B. Benzene in drinking water
C. Chromium (hexavalent) in drinking water
D. Drinking water contaminated with nitrate

Answer 13

D. Drinking water contaminated with nitrate

Question 14

The EPA provides guidance on how to sample for toxicants in the environment and describes several different sampling techniques paying particular attention to their benefits, costs and limitations. One of the more efficient methods when dealing with incomplete data about the source of contamination is the adaptive cluster sampling method. Anyone familiar with the game Battleship has almost certainly practiced this sampling method. Which of the answers below shows this type of sampling?
A. Random patterns
B. Organized grid
C. Initial clustering then random sampling outward
D. Focused clustering

Answer 14

C. Initial clustering then random sampling outward

Question 15

Extractables & Leachables studies and cytotoxicity studies for medical devices involve using different solvents and medium to try and determine what chemicals might leach out of a medical device and if they might be toxic. Which of the commonly used solvents/medium is used in “exhaustive” extraction because it’s such a strong solvent it can quickly cause plastic parts to fall apart?

A. 40% ethanol
B. Cell-culture medium
C. Hexane
D. Water

Answer 15

C. Hexane

Question 16

Substances of Very High Concern, SVHCs have been identified by ECHA as having characteristics that make them a toxicological concern. In spite of being persistent in the environment and bioaccumulating in humans, Perfluorooctanoic acid (PFOA) was not classified as just PB or vPvB. Why was this not the classification?
A. It’s carcinogenic so it was classified as CMR
B. It’s mutagenic so it was classified as CMR
C. It’s non-toxic so it wasn’t classified
D. It’s toxic to reproduction so it was classified as both PBT and a CMR

Answer 16

D. It’s toxic to reproduction so it was classified as both PBT and a CMR

Question 17

A clinical trial is designed to example both primary and secondary pharmacology as well as benefit and harm. What would be an example of a reported response being an example of biological significance that lacks toxicological significance.

A. Antineoplastic drug fails to have any partial or complete responses in any of the cancer patients, but several patients develop serious adverse events (e.g., anemia, emesis)
B. Blood pressure medication is effective to the point that they are no longer considered hypertensive but there are also no reports of hypotension
C. Cardiac arrhythmia occurs in some patients whose anti-histamine also reduced the severity of their allergies
D. Dilaudid (hydromorphone hydrochloride) causes analgesia in all of the patients but also causes hyperalgesia and dependence in many of them too

Answer 17

B. Blood pressure medication is effective to the point that they are no longer considered hypertensive but there are also no reports of hypotension

Question 18

Intrauterine Devices (IUDs) are an unusual form of contraception both because for years at a time they remove the problem of patient non-compliance. They are also noteworthy because when provided for free they have been shown to significantly reduce both unplanned pregnancies and subsequent abortions. And while the metal based IUD relies on ion release and surface interactions, the hormonal IUDs deliver a contraceptive drug. What is true about these IUDs.

A. Aluminum ions make the metal IUDs work while a progestin is used to make the hormonal ones work
B. Beryllium ions make the metal IUDs work while a progestin is used to make the hormonal ones work
C. Copper ions make the metal IUDs work while a progestin is used to make the hormonal ones work
D. Delivery of iron ions makes the metal IUDs work while a progestin is used to make the hormonal ones work

Answer 18

C, Copper ions make the metal IUDs work while a progestin is used to make the hormonal ones work

Question 19

The dose makes the poison and because toxicity can range over many orders of magnitude, Toxicologists often use logarithmic scales. What would 2 be equal to when shown plotted on a log10 scale (i.e., the antilog10 of 2)?

A. 1
B. 10
C. 100
D. 1000

Answer 19

C. 100

Question 20

While all of these organizations relate to toxicology in one way or another because of the scope of their regulations, one of them is solely focused on how animals and not people might be exposed to chemicals and is specific to the United States. Similar organizations exist in other countries, but they often have different names and organizational structures. Which organization fits this description? What are the others?

A. IACUC
B. IATA
C. ICH
D. ISO

Answer 20

A. IACUC

IATA refers to Integrated Approaches to Testing and Assessment

ICH is the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.

ISO is the International Organization for Standardization

Question 21

The Wizard of Oz movie was filmed long before modern movie safety standards were put into place. There were several chemical exposures that would not have been allowed today. What was not an issue on the set associated with using toxic makeup chemicals?

A. Aluminum paint caused Jack Haley (Tin Man) to have eye irritation that eventually became an infection
B. Brown iron oxides put on Bert Lahr (Cowardly Lion) and Ray Bolger (Scarecrow) caused corrosive skin burns
C. Copper used to make Margaret Hamilton (Wicked Witch) look green meant the actress had to sometimes be fed her meals to avoid copper poisoning
D. Dusting Buddy Epsen (the first Tin Man) with aluminum powder almost killed him and he had to be rushed to the hospital to get help breathing

Answer 21

D. Dusting Buddy Epsen (the first Tin Man) with aluminum powder almost killed him and he had to be rushed to the hospital to get help breathing

Question 22

Which regulatory agency is not one of the three governing bodies that made up the originally tripartite structure of ICH which has now expanded to include many more governing bodies?

A. EMA (Europe)
B. FDA (US)
C. PMDA (Japan)
D. TGA (Australia)

Answer 22

D. TGA (Australia)

The International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation (ICH) held the inaugural Assembly meetings on 23 October 2015 establishing ICH as an international association, a legal entity under Swiss law.

Harmonisation of regulatory requirements was pioneered by the EC, Europe, in the 1980s, as the EC, Europe moved towards the development of a single market for pharmaceuticals. The success achieved in Europe demonstrated that harmonisation was feasible. At the same time there were discussions between Europe, Japan and the US on possibilities for harmonisation. It was, however, at the WHO Conference of Drug Regulatory Authorities (ICDRA), in Paris, in 1989, that specific plans for action began to materialise. Soon afterwards, the authorities approached International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) to discuss a joint regulatory-industry initiative on international harmonisation, and ICH was conceived.

Question 23

Poison ivy (Toxicodendron radicans) is a major cause of delayed type hypersensitivity reactions. As such people often try and remove it from residential areas. What way is not a recommended means of removal?

A. Adding herbicide as poison ivy is completely resistant to all of them
B. Burning the plants as it can cause a potential lethal allergic reaction inside the lungs if the uroshiol is inhaled
C. Cutting the vines carefully and composting them as even bacteria cannot break down uroshiol and it can be spread in the garden
D. Deploying goats as they are even more sensitive to poison ivy than people

Answer 23

B, Burning the plants as it can cause a potential lethal allergic reaction inside the lungs if the uroshiol is inhaled

Question 24

The size of the volume of distribution for the anesthetic propofol helps to explain both its rapid distribution and efficacy. The volume of distribution for propofol is one of the answers is listed down below. Which one is correct for a 70 kg adult?

A. 0.06 Liters
B. 0.6 Liters
C. 6 Liters
D. 4200 Liters

Answer 24

D. 4200 Liters

The volume of distribution (Vd) is the apparent fluid volume occupied by a chemical. Vd<1 implies hydrophilic substances while hydrophobic substances have Vd>1. High values imply rapid uptake into tissues.

Question 25

28. ICH Q3D R(1) lists permissible daily exposures (PDEs) for metals (e.g., cadmium, thallium). However the metal calcium is left out of the appendix. Why?

A. It’s highly toxic so there is no permissible level
B. It’s moderately toxic so there are regional differences about what is permissible
C. It’s essentially non-toxic so there are no limitations needed
D. It’s an essential nutrient so recommended daily allowances are generally used instea

Answer 25

D, It’s an essential nutrient so recommended daily allowances are generally used instead

Question 26

The recent results of a Phase I clinical trial against rectal cancer made history when after at least 6 month of treatment 12/12 treated patients had a complete response. What else about this trial while normal for a cancer trial is unusual for a Phase I trial?

A. Adults but not children were treated
B. Biological mechanisms of action were already understood based on preclinical models and patient selection
C. Clinical efficacy was an endpoint
D. Drug was tested on fewer than 20 participants

Answer 26

C. Clinical efficacy was an endpoint

Question 27

Asbestos causes mesotheliomas in the lung through what mechanism?

A. Long fibers too big to be removed by macrophages get trapped in the lungs cause chronic inflammation that leads to carcinogenesis
B. Large surface area of nanoparticles generates reactive oxygen species causing chronic inflammation that leads to carcinogenesis
C. Asbestos contains carcinogens (e.g., benzo(a)pyrene) that leach out leading to carcinogen
D. Asbestos only causes mesotheliomas in the gut and not the lungs

Answer 27

A, Long fibers too big to be removed by macrophages get trapped in the lungs cause chronic inflammation that leads to carcinogenesis

This is referred to as “frustrated phagocytosis” where ROS are formed and cause DNA damage. Certain forms of asbestos contain iron that contribute to Fenton reaction.

Question 28

The CYPs are generally known as monooxygenases. As a group they can oxidize and metabolize a wide range of both endogenous compounds and xenobiotics. However, they also can function as redox enzymes and can either oxidize or reduce the same substrate depending on the conditions. This can been seen with the dehalogenation of halothane by CYP2A6 in the human liver. When this happens by reduction what is added during the dehalogenation process that becomes part of the new metabolite?

A. A hydrogen atom
B. An oxygen atom
C. A positive charge
D. Nothing is added

Answer 28

A. A hydrogen atom

OIL RIG

Phase I biotransformation (non-conjugation reaction). Reductive dehalogenation swaps a halogen for H, whereas oxidative dehalogenation swaps a hydrogen and a halogen for a double bonded oxygen.

Question 29

A TI is being calculated for a chemical based on a NOAEL reported in an oral animal study. Per ICH a default allometric scaling factor of 4 was used to address interspecies differences. But an additional factor of 2.5 was added to address additional species differences. What conditions would support these numbers?

A. Rabbit was used and based on metabolism is predicted to be less susceptible than humans
B. Rabbit was used and based on metabolism is predicted to be more susceptible than humans
C. Rat was used and based on metabolism is predicted to be less susceptible than humans
D. Rat was used and based on metabolism is predicted to be more susceptible than humans

Answer 29

C. Rat was used and based on metabolism is predicted to be less susceptible than humans

Rats are 4, rabbits are 2.3, monkeys are 2, mice are 7. the 2.5 accounts for “other” differences.

Question 30

The US FDA and other regulatory agencies require cGMP to be followed in the manufacturing of food, drugs and cosmetics to avoid harm to the public. During the COVID-19 pandemic there was a problem in the United States where alcohol-based hand-sanitizers were found to contain toxic methanol instead of the safer but more expensive to manufacture ethanol. A decade or so earlier a similar situation occurred where melamine was used in pet food and infant formula as a way to pass the products off as full of protein without having to purchase the protein and amino acids needed for growing puppies and babies. These cases of intentional substitution of toxic inferior raw materials are examples of what kind of crime?

A. Adulteration
B. Bribery
C. Cross-contamination
D. Denaturing

Answer 30

A. Adulteration

Question 31

What is not a term used to describe the follow-up surveillance activity towards a newly approved pharmaceutical?

A. Pharmacovigilance
B. Phase III
C. Phase IV
D. Post-marketing surveillance

Answer 31

B. Phase III

Question 32

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 32

B, Carbon disulfide and n-hexane

These target the neuron, causing cross-linkages between axon filaments. Metabolism of carbon disulfide via the thiourea pathway results in accumulative damage (irreversible crosslinks).

Question 33

Acetaminophen (aka paracetamol) is a major cause of liver failure worldwide particularly in countries that do not restrict its availability. What mechanism is most often used to try and reduce liver damage after an overdose when timing and blood levels indicate treatment is needed to preserve liver function?

A. Activator of PXR is administered to increase CYP expression and subsequent elimination
B. Blood transfusion is administered to increase elimination
C. Cofactor is administered to increase conjugation and subsequent elimination
D. Dialysis is administered to increase elimination

Answer 33

C, Cofactor is administered to increase conjugation and subsequent elimination

The cofactor is Acedadote (acetylcysteine). Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity. Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.

Question 34

36. ICH S5 gives guidance on DART studies with the aim to address the whole life cycle of an organism going from conception to conception. How many generations are involved in this type of approach?
    A. 1
    B. 2
    C. 3
    D. 4

Answer 34

C. 3

F0, F1 and F2. F2 includes the oocytes of females in the F1 as these are formed during gestation.

Question 35

Current Good Manufacturing Practices (cGMP) vary somewhat by region. Most regulatory agencies require dedicated facilities to produce beta-lactam antibiotics. But essentially all of them require this for penicillin. Why is the purpose for keeping the penicillin producing equipment and facilities separated?

A. Avoiding anaphylaxis and allergic reactions caused by cross contamination
B. Blocking bronchorrhea, bronchospasm, and bradycardia caused by cross contamination
C. Ceasing cancers caused by cross contamination
D. Denying developmental delays or defects caused by cross contamination

Answer 35

A. Avoiding anaphylaxis and allergic reactions caused by cross contamination

Immunotoxicity is due to the formation of neoantigens. Metabolism of penicillin produces a “hapten” which is a small molecule bound to a protein that triggers a response from the immune system.

Question 36

As per ICH M3 (R1) what group generally requires the most testing to have been completed prior to their being enrolled in a clinical trial where they will be given a new investigational pharmaceutical.

A. Adolescents and women of child-bearing potential
B. Boys and Men
C. Cancer patients with limited life-expectency
D. Developing embryos/ fetuses and their mothers

Answer 36

D. Developing embryos/ fetuses and their mothers

Question 37

Memorial day is a US holiday to honor soldiers who died while serving the US armed forces. What oxidizing, irritating and lung damaging chemical was first used as a chemical warfare agent against Allied soldiers in WWI, was used much more recently in Syria against civilians, and can be accidentally produced by combining certain household cleaners?

A. Ammonia
B. Bromine gas
C. Chlorine gas
D. Dioxin

Answer 37

C, Chlorine gas

Common household combinations include bleach and various acids (acetic acid, certain cleaners). Inhaled chlorine gas forms hydrochloric acid and bleach in the lung mucosa leading to irritation and necrosis of tissue.

Question 38

If based on the chemical structure and what is already known about related compounds low toxicity is expected for a type of organism (e.g., earthworm, daphnia magna, mouse) for a test chemical what type of acute toxicity test is generally recommended be tried first by OECD?

A. LC50
B. LD50
C. Limit test
D. Main test

Answer 38

C. Limit test

The limit test can be used efficiently to identify chemicals that are likely to have low toxicity. The test substance is administered generally in a single dose by gavage to animals fasted prior to dosing.

Question 39

Stability testing is required for pharmaceuticals by regulators across the globe. How does ICH primarily relate stability testing to toxicity and carcinogenicity?

A. Active Pharmaceutical Ingredients (APIs) losing potency and not being as effective as antidotes and antineoplastics.
B. Breakdown products causing toxicity and carcinogenicity when shelf-life or storage conditions are exceeded
C. Component appearance changing (e.g., yellowing) when shelf-life or storage conditions are exceeded
D. Doesn’t get related by ICH

Answer 39

B, Breakdown products causing toxicity and carcinogenicity when shelf-life or storage conditions are exceeded

Question 40

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 40

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

Pregnancy and Lactation Labeling Rule (PLLR).

Question 41

What is the appropriate order for normal pharmaceutical development?

A. Basic research, clinical trials, post-market surveillance, preclinical trials
B. Basic research, clinical trials, preclinical trials, post-market surveillance
C. Basic research, pre-clinical trials, clinical trials, post-market surveillance
D. Pre-clinical trials, basic research, post-market surveillance, clinical trials

Answer 41

C. Basic research, pre-clinical trials, clinical trials, post-market surveillance

Question 42

Endotoxins are released when gram negative bacteria cell walls break down into smaller pieces. They can trigger the innate immune response. What is NOT an expected response?

A. Anaphylactic reactions
B. Body temperature reduction
C. Complement activation
D. Death

Answer 42

B. Body temperature reduction

Question 43

Cost is always an issue in terms of sampling for contaminants in the environment. In terms of deciding when to start remediation for a defined area that is owned by an organization what is NOT a way to limit the number of samples needed?

A. Increasing the alpha
B. Increasing the beta
C. Sequential sampling to compare an average to a threshold
D. Systematic grid sampling

Answer 43

D. Systematic grid sampling

Question 44

OECD 442B covers how to perform the local lymph node assay. This can be done using an ELISA or flow-cytometry to measure the number of proliferating cells. Proliferating cells are identifiable because they uptake what compound?

A. Adenosine
B. BrdU
C. Congo Red
D. DNA

Answer 44

B. BrdU

The Local Lymph Node Assay: BrdU-ELISA (LLNA:BrdU-ELISA) is a non-radioactive modification to the LLNA method for identifying potential skin sensitizing test substances and measuring the proliferation of lymphocytes they induce in the auricular lymph nodes.

BrdU is 5-bromo-2-deoxyuridine, an analogue of thymidine, and its uptake is used as an indicator of proliferation.

Question 45

What is true about placebos with respect to clinical trials?

A. They are always required in a study even to determine equivalence
B. They are always the only treatment given to a patient in that treatment arm
C. They never demonstrate any efficacy with respect to the patients receiving no treatment for any condition
D. They never include an active pharmaceutical ingredient (API)

Answer 45

D. They never include an active pharmaceutical ingredient (API)

Question 46

Rare cases of relatively young and healthy people developing major lung damage requiring ECMO after being treated for infections with a widely used antibiotic combination (sulfamethoxazole and trimethoprim) have been reported. The lung infiltrates detected suggest an immune response. These drugs have also been associated with rare cases of severe dermal toxicities (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis). What type of toxicity do these reactions represent?

A. Allergenic and anaphylactic
B. Iatrogenic and idiosyncratic
C. Predictable and preventable
D. Rapid and respiratory

Answer 46

B. Iatrogenic and idiosyncratic

Question 47

Limit tests are used to reduce the number of animals needed for acute toxicity testing. What is the smallest number of animals that have to die before a limit test is stopped and the main test is started?

A. 1
B. 2
C. 5
D. 10

Answer 47

A. 1

Limit test is part of the “Up-and-Down Procedure” of OECD 425 Guideline for acute toxicity testing. Test dose is usually @ 2000 mg/kg but occasionally a higher dose of 5000 mg/kg may be allowed in certain instances. In either case, test animals (preferably female rats) are dosed one at a time at the selected test dose. If the first animal dies, then the main test is conducted to determine the LD50. If the animal survives, four additional animals are dosed sequentially until a total of five animals are tested (i.e. n= 5 as the upper limit of animals tested).

Question 48

Screening is being conducted for a metabolism disorder that results in permanent brain damage to the developing child if they are not diagnosed early on. The main treatment is dietary restriction that consists of limiting the presence of a single essential amino acid to only what is necessary. While for any assay having both high true positive and high true negative rates is ideal, for this type of condition where a severe toxicity can result from a false positive the true positive rate needs to be maximized. What would the developer of that type of assay be looking for primarily?

A. High selectivity
B. High sensitivity
C. Low selectivity
D. Low sensitivity

Answer 48

B. High sensitivity

Question 49

Putting parrotfish on your plate can cause paresthesia as part of ciguatera poisoning. Paresthesia is also associated with what kind of pesticide?

A. Paraquat and other quaternary ammonium herbicides
B. Parathion and other organophosphate insecticides
C. Permethrin and other pyrethroid insecticides
D. Piperonyl butoxide and other synergists

Answer 49

C. Permethrin and other pyrethroid insecticides