Non-clinical drug development – pharmacology and toxicology studies MCQs With Answer

Non-clinical drug development integrates pharmacology and toxicology studies to define a drug’s safety, pharmacodynamic effect and ADME profile before human trials. For B.Pharm students, mastering preclinical study types—safety pharmacology, toxicokinetics, genotoxicity, carcinogenicity, reproductive toxicity and GLP-compliant repeat-dose studies—is essential. These studies use in vitro assays (hERG, receptor binding), in vivo models, histopathology and biomarkers to determine endpoints such as NOAEL, MTD and LD50, support dose selection and meet regulatory guidance (ICH, OECD). A deeper grasp of study design, interpretation and regulatory expectations prepares you for roles in drug safety assessment and submissions. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which study primarily identifies target organ toxicity during non-clinical drug development?

• Single-dose pharmacokinetic study
• Repeat-dose toxicity study
• In vitro receptor binding assay
• Bioavailability study

Correct Answer: Repeat-dose toxicity study

Q2. What does GLP ensure in non-clinical pharmacology and toxicology studies?

• Faster study completion
• Standardized laboratory animal diets
• Reliability, traceability and regulatory acceptability of data
• Lower study costs

Correct Answer: Reliability, traceability and regulatory acceptability of data

Q3. NOAEL stands for which of the following?

• No Observed Adverse Effect Level
• No Observable Acute Effect Limit
• Negative Observed Activity Experimental Limit
• New Observation of Adverse Event Level

Correct Answer: No Observed Adverse Effect Level

Q4. The LD50 value refers to what measure?

• The dose causing therapeutic effect in 50% subjects
• The dose causing lethality in 50% of test animals
• The dose producing 50% receptor occupancy
• The dose cleared in 50% of plasma within an hour

Correct Answer: The dose causing lethality in 50% of test animals

Q5. MTD in toxicology denotes:

• Most tolerated duration
• Maximum tolerated dose
• Minimum toxic dose
• Mean therapeutic dose

Correct Answer: Maximum tolerated dose

Q6. The core battery of safety pharmacology typically assesses which organ systems?

• Gastrointestinal, endocrine and immune
• Central nervous, cardiovascular and respiratory
• Renal, hepatic and musculoskeletal
• Dermatologic, ocular and auditory

Correct Answer: Central nervous, cardiovascular and respiratory

Q7. Which in vitro test is commonly used to detect bacterial mutagenicity?

• Micronucleus assay
• Ames test
• Comet assay
• hERG assay

Correct Answer: Ames test

Q8. The in vivo micronucleus test primarily detects which type of damage?

• Protein denaturation
• Chromosomal damage or aneugenic/clastogenic effects
• Hepatocellular necrosis
• Cardiac arrhythmia

Correct Answer: Chromosomal damage or aneugenic/clastogenic effects

Q9. Which ICH guideline is focused on genotoxicity testing strategies?

• ICH S7A
• ICH S1
• ICH S2(R1)
• ICH M3(R2)

Correct Answer: ICH S2(R1)

Q10. Developmental and reproductive toxicity (DART) testing typically includes which study types?

• Single-dose toxicity only
• Fertility, embryo‑fetal development and pre/postnatal studies
• Mutagenicity and carcinogenicity only
• Pharmacokinetic profiling in microbes

Correct Answer: Fertility, embryo‑fetal development and pre/postnatal studies

Q11. Typical duration for rodent carcinogenicity studies is:

• 3 months
• 6 months
• 1 year
• 2 years

Correct Answer: 2 years

Q12. Toxicokinetic studies in toxicity testing measure:

• Behavioral responses in animals
• Plasma and tissue exposure of the test article under dosing conditions
• Only urinary excretion rates
• In vitro receptor binding affinity

Correct Answer: Plasma and tissue exposure of the test article under dosing conditions

Q13. ADME in preclinical studies stands for:

• Activity, Distribution, Metabolism, Efficacy
• Absorption, Distribution, Metabolism, Excretion
• Administration, Dosage, Metabolism, Elimination
• Affinity, Disposition, Molecular weight, Excretion

Correct Answer: Absorption, Distribution, Metabolism, Excretion

Q14. A major limitation of in vitro toxicity assays compared to in vivo studies is:

• Higher throughput capability
• Lack of ADME and whole‑organism responses
• Lower sensitivity to cytotoxic compounds
• Excessive regulatory acceptance

Correct Answer: Lack of ADME and whole‑organism responses

Q15. Regulatory repeat‑dose toxicity studies typically use how many mammalian species?

• One species only
• Two species (usually one rodent and one non‑rodent)
• Three species including birds
• Only non‑mammalian species

Correct Answer: Two species (usually one rodent and one non‑rodent)

Q16. The primary purpose of non‑clinical pharmacology studies is to:

• Evaluate commercial manufacturing processes
• Demonstrate mechanism of action and pharmacodynamic effects
• Replace clinical trials entirely
• Measure human therapeutic benefit

Correct Answer: Demonstrate mechanism of action and pharmacodynamic effects

Q17. Which outcome is most directly assessed by histopathology in toxicity studies?

• Plasma drug concentration
• Tissue-level lesions and microscopic organ changes
• Drug potency at the receptor
• Stability of formulation

Correct Answer: Tissue-level lesions and microscopic organ changes

Q18. Difference between NOEL and NOAEL is that NOEL refers to:

• No Observed Effect Level (may include non-adverse effects)
• No Observed Adverse Effect Level (only adverse effects)
• New Observational Experimental Limit
• Normal Observational Exposure Limit

Correct Answer: No Observed Effect Level (may include non-adverse effects)

Q19. Toxicogenomics adds which dimension to conventional toxicology?

• Gene expression and molecular pathway analysis
• Only histological scoring
• Extended clinical observation times in humans
• Increased animal cohort sizes without molecular data

Correct Answer: Gene expression and molecular pathway analysis

Q20. Selection of a safe starting dose for first‑in‑human studies commonly uses which metric?

• Therapeutic dose in animals
• NOAEL from the most sensitive species with appropriate safety factors
• LD50 divided by two
• Arbitrary fraction of the marketed dose

Correct Answer: NOAEL from the most sensitive species with appropriate safety factors

Q21. In vitro studies for CYP enzyme inhibition are primarily used to predict:

• Carcinogenic potential
• Drug–drug interaction risk via metabolic pathways
• Dermal irritation
• Reproductive toxicity

Correct Answer: Drug–drug interaction risk via metabolic pathways

Q22. Which hematological parameter is routinely evaluated in repeat‑dose toxicity studies?

• Bone mineral density only
• Red blood cell count and hemoglobin
• Skin pH
• Cerebrospinal fluid glucose only

Correct Answer: Red blood cell count and hemoglobin

Q23. OECD test guidelines are important in non‑clinical studies because they:

• Provide standardized international study protocols accepted by regulators
• Are only suggestions with no regulatory value
• Apply only to clinical human trials
• Prescribe commercial pricing for testing

Correct Answer: Provide standardized international study protocols accepted by regulators

Q24. Metabolite safety testing focuses on human metabolites that are:

• Present at negligible levels in humans
• Present at significant levels compared with animal species
• Only present in animal plasma
• Unstable in vitro

Correct Answer: Present at significant levels compared with animal species

Q25. The guideline addressing safety pharmacology studies for human pharmaceuticals is:

• ICH S7A
• ICH Q1A
• ICH E6(R2)
• ICH M4

Correct Answer: ICH S7A

Q26. Embryo‑fetal development studies are normally conducted in:

• Only in vitro zebrafish embryos
• Two species, typically one rodent and one non‑rodent
• Only in humans
• Three generations of plants

Correct Answer: Two species, typically one rodent and one non‑rodent

Q27. The in vitro hERG assay is used to assess risk of:

• Hepatotoxicity
• QT interval prolongation and torsades risk
• Nephrotoxicity
• Embryotoxicity

Correct Answer: QT interval prolongation and torsades risk

Q28. Acute toxicity studies differ from chronic toxicity studies primarily by:

• Route of administration only
• Duration of exposure and endpoints evaluated
• Use of in vitro models only
• Regulatory irrelevance of results

Correct Answer: Duration of exposure and endpoints evaluated

Q29. An early biochemical biomarker commonly used to detect liver injury in toxicity studies is:

• ALT (alanine aminotransferase)
• Serum creatinine only
• Blood glucose exclusively
• Procalcitonin

Correct Answer: ALT (alanine aminotransferase)

Q30. Compliance with GLP in non‑clinical studies primarily facilitates:

• Patent approval for the drug
• Regulatory acceptance of study data and study reproducibility
• Faster patient recruitment in clinical trials
• Exemption from toxicity testing

Correct Answer: Regulatory acceptance of study data and study reproducibility

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com