In vivo carcinogenicity study design and interpretation MCQs With Answer

Introduction: This blog provides a focused set of in vivo carcinogenicity study design and interpretation MCQs tailored for M.Pharm students preparing for exams and practical applications. The questions cover regulatory guidance, rodent bioassay design, dose selection, transgenic models, pathology evaluation, statistical analyses, and interpretation challenges such as historical control data and mode-of-action considerations. Each item targets critical decision points encountered in planning or reviewing long-term carcinogenicity studies, emphasizing GLP/OECD principles, survival-adjusted analyses, and translational relevance to humans. Answers are included to reinforce learning and aid rapid revision for coursework, viva voce, and research project planning.

Q1. What is the commonly recommended maximum duration for a standard rodent carcinogenicity bioassay in OECD TG 453?

• 6 months
• 12 months
• 18 months
• 24 months

Correct Answer: 24 months

Q2. In designing an in vivo carcinogenicity study, what does MTD stand for and why is it important?

• Maximum Tolerated Dose; to ensure animals receive non-toxic exposures only
• Median Toxic Dose; to estimate the LD50
• Maximum Tolerated Dose; to provide the highest dose that does not cause excessive systemic toxicity
• Minimum Test Dose; to define the lowest biologically active dose

Correct Answer: Maximum Tolerated Dose; to provide the highest dose that does not cause excessive systemic toxicity

Q3. Which statistical approach is most appropriate to adjust for differences in survival when comparing tumor incidences between groups?

• Fisher’s exact test without adjustment
• Poly-k test
• ANOVA for proportions
• Kaplan-Meier without tumor adjustment

Correct Answer: Poly-k test

Q4. Which animal strain is most commonly used for two-year carcinogenicity bioassays in regulatory studies?

• Wistar rat
• B6C3F1 mouse
• Sprague-Dawley rat
• CD-1 mouse

Correct Answer: B6C3F1 mouse

Q5. When is a transgenic mouse model (e.g., Tg.AC or p53+/-) typically preferred over a traditional two-year bioassay?

• To replace chronic toxicity testing entirely
• For short-term rapid screening of carcinogenic potential or when time/resources are limited
• When human epidemiology data are definitive
• To assess compound reproductive toxicity

Correct Answer: For short-term rapid screening of carcinogenic potential or when time/resources are limited

Q6. What is the primary purpose of including historical control data in carcinogenicity study interpretation?

• To provide animal welfare metrics for cage enrichment
• To compare tumor incidences with past control ranges and help interpret unexpected findings
• To replace the concurrent control group when budget is limited
• To validate analytical chemistry methods for dosing

Correct Answer: To compare tumor incidences with past control ranges and help interpret unexpected findings

Q7. Which guideline specifically describes combined chronic toxicity/carcinogenicity study designs for rats?

• OECD TG 420
• OECD TG 453
• OECD TG 451
• OECD TG 443

Correct Answer: OECD TG 453

Q8. In mode-of-action (MOA) analysis for tumor formation, which element is least relevant?

• Key events between exposure and tumor formation
• Species concordance of the MOA
• Biochemical plausibility and dose-response concordance
• Vehicle palatability for dose administration

Correct Answer: Vehicle palatability for dose administration

Q9. Which is a common pitfall when interpreting tumor findings from in vivo carcinogenicity studies?

• Over-reliance on concurrent control data only
• Failing to consider spontaneous strain-specific tumor incidences
• Using both sexes and multiple doses
• Applying survival-adjusted statistics

Correct Answer: Failing to consider spontaneous strain-specific tumor incidences

Q10. What is the preferred route of administration for chronic carcinogenicity testing to mimic human oral exposure to a food additive?

• Intravenous bolus
• Inhalation exposure
• Dietary administration
• Topical application

Correct Answer: Dietary administration

Q11. Which tumor metric specifically estimates the dose associated with a 50% increase in tumor incidence over background?

• NOAEL
• TD50
• LD50
• LOAEL

Correct Answer: TD50

Q12. Which practice improves the objectivity of pathology interpretation in carcinogenicity studies?

• Single pathologist reads all slides without peer review
• Blinded peer review and pathology working groups with consensus diagnoses
• Using only historical control diagnoses
• Reviewing only gross lesions and ignoring microscopic assessment

Correct Answer: Blinded peer review and pathology working groups with consensus diagnoses

Q13. In a two-year study a marginal increase in a rare tumor type is seen only at the high dose. Which consideration most strengthens causality?

• High-dose animals had poor feed consumption
• Similar tumor increases are seen in multiple species and sexes with a dose-related trend
• Control group had unusually low survival
• The tumor is common in this strain

Correct Answer: Similar tumor increases are seen in multiple species and sexes with a dose-related trend

Q14. Which regulatory concept describes extrapolating animal tumor data to human risk using mechanistic understanding?

• Historical control comparison
• Mode-of-action (MOA) and human relevance framework
• Maximum tolerated dose scaling
• LD50 extrapolation

Correct Answer: Mode-of-action (MOA) and human relevance framework

Q15. What is the role of positive control substances in short-term carcinogenicity screens or genotoxicity tests?

• To prove the test system is competent to detect known carcinogenic or genotoxic responses
• To compare potency with the test article for human risk assessment
• To reduce animal numbers in the study
• To act as a vehicle for the test compound

Correct Answer: To prove the test system is competent to detect known carcinogenic or genotoxic responses

Q16. Which survival analysis method is frequently used to compare time-to-tumor or overall survival between groups?

• Chi-square test for trend
• Cox proportional hazards model
• Student’s t-test
• Bartlett’s test

Correct Answer: Cox proportional hazards model

Q17. When dose concentrations are limited by solubility or palatability, what is an appropriate design adaptation?

• Terminate study early to avoid complications
• Use gavage at high bolus doses regardless of human relevance
• Select lower but biologically meaningful doses and justify in rationale, possibly using additional mechanistic endpoints
• Increase animal numbers instead of adjusting doses

Correct Answer: Select lower but biologically meaningful doses and justify in rationale, possibly using additional mechanistic endpoints

Q18. Which finding would most likely indicate a non-genotoxic (epigenetic or proliferative) mode of action for tumor induction?

• Positive mutagenicity in bacterial reverse mutation assay
• Direct DNA adduct formation detected at low doses
• Sustained cell proliferation and regenerative hyperplasia preceding tumor formation
• Dose-related chromosomal breaks in bone marrow

Correct Answer: Sustained cell proliferation and regenerative hyperplasia preceding tumor formation

Q19. Which parameter is critical to document to ensure GLP-compliant carcinogenicity studies?

• Only the final tumor list
• Comprehensive raw data, SOPs, chain-of-custody for samples, and audit trails
• Only dosing records
• Only histopathology reports without slide identifiers

Correct Answer: Comprehensive raw data, SOPs, chain-of-custody for samples, and audit trails

Q20. For interpreting low-incidence tumors in treated animals, which combination of evidence best supports a treatment-related effect?

• Single affected animal and no biological plausibility
• Dose-response trend, statistical significance (survival-adjusted), corroborating mechanistic data, and difference from concurrent and historical controls
• Only historical control outlier matching the treated incidence
• Tumors only in an ancillary interim sacrifice group

Correct Answer: Dose-response trend, statistical significance (survival-adjusted), corroborating mechanistic data, and difference from concurrent and historical controls

Download