Toxicity tests: sub-acute MCQs With Answer

Introduction:

This blog provides a focused set of sub-acute toxicity MCQs tailored for M.Pharm students studying Biological Evaluation of Drug Therapy. Sub-acute toxicity studies (typically 28 days) bridge acute and chronic evaluations, revealing dose-related effects, target organs, and early biomarkers of toxicity. The questions below cover study design, regulatory guidelines (e.g., OECD), selection of species and dose levels, endpoints such as clinical observations, body/organ weight changes, hematology, clinical chemistry, histopathology, toxicokinetics, NOAEL/LOAEL determination, and interpretation of recovery groups. Use these MCQs to deepen conceptual understanding, prepare for examinations, and reinforce practical considerations in conducting and interpreting sub-acute toxicity studies.

Q1. Which duration most commonly defines a sub-acute (repeat-dose) toxicity study in rodents according to standard regulatory practice?

• 7 days
• 14 days
• 28 days
• 90 days

Correct Answer: 28 days

Q2. The primary objective of a sub-acute toxicity study is to:

• Evaluate carcinogenic potential after lifetime exposure
• Identify immediate lethal dose after single administration
• Characterize toxic effects and dose–response after repeated dosing over weeks
• Assess reproductive effects across multiple generations

Correct Answer: Characterize toxic effects and dose–response after repeated dosing over weeks

Q3. Which guideline is most commonly referenced for conducting 28-day repeated dose toxicity studies?

• ICH S1
• OECD Test Guideline 407
• ICH Q3A
• ICH S9

Correct Answer: OECD Test Guideline 407

Q4. In designing dose groups for a sub-acute study, the highest dose is usually selected to produce which of the following without causing excessive mortality?

• No observable effects at all
• Marked therapeutic benefit
• Systemic toxicity and clear adverse effects
• Only local irritation at the administration site

Correct Answer: Systemic toxicity and clear adverse effects

Q5. Which parameter is considered a sensitive early marker of hepatic injury in sub-acute toxicity studies?

• Serum creatinine
• Alanine aminotransferase (ALT)
• Hemoglobin concentration
• Alkaline phosphatase in urine

Correct Answer: Alanine aminotransferase (ALT)

Q6. Inclusion of a recovery group in a 28-day study is primarily intended to assess:

• Acute mortality only
• Persistence and reversibility of toxic effects after dosing stops
• Pharmacodynamic efficacy at low doses
• Mutagenic potential of the test article

Correct Answer: Persistence and reversibility of toxic effects after dosing stops

Q7. Which of the following is the best definition of NOAEL in sub-acute toxicity studies?

• The highest dose that produces a predefined toxic effect
• The lowest dose at which any adverse effect is observed
• The highest dose at which no treatment-related adverse effects are observed
• The single dose that is lethal to 50% of animals

Correct Answer: The highest dose at which no treatment-related adverse effects are observed

Q8. When selecting animal species for a sub-acute toxicity study, regulatory practice commonly requires two mammalian species. Which pair is most frequently used?

• Rabbit and guinea pig
• Dog and monkey
• Rat and non-rodent (usually dog or minipig)
• Mouse and hamster

Correct Answer: Rat and non-rodent (usually dog or minipig)

Q9. Which endpoint provides quantitative information on organ-specific effects and is routinely recorded at necropsy in sub-acute studies?

• Clinical sign scoring
• Organ weight measurement (absolute and relative)
• Food palatability testing
• Behavioral maze performance

Correct Answer: Organ weight measurement (absolute and relative)

Q10. Toxicokinetic assessments in sub-acute studies are important because they:

• Replace the need for histopathology
• Determine exposure–response relationships and accumulation over time
• Are only necessary for topical formulations
• Measure only urinary excretion of unchanged drug

Correct Answer: Determine exposure–response relationships and accumulation over time

Q11. Which of the following hematological changes in a 28-day study would most likely suggest bone marrow suppression?

• Erythrocytosis with increased hematocrit
• Thrombocytopenia and leukopenia
• Eosinophilia only
• Isolated increase in mean corpuscular volume

Correct Answer: Thrombocytopenia and leukopenia

Q12. A limit test in a sub-acute study is typically used when prior data indicate low toxicity. Which dose is commonly employed as a limit dose?

• 1 mg/kg/day
• 50 mg/kg/day
• 1000 mg/kg/day
• 10,000 mg/kg/day

Correct Answer: 1000 mg/kg/day

Q13. Which histopathological finding in the kidney after repeated dosing most directly indicates proximal tubular injury?

• Glomerular hypercellularity
• Proteinaceous casts and tubular epithelial cell necrosis
• Interstitial fibrosis without tubular change
• Vascular congestion only

Correct Answer: Proteinaceous casts and tubular epithelial cell necrosis

Q14. For systemic compounds, which route of administration is most commonly used in rodent 28-day toxicity studies to mimic clinical exposure?

• Intramuscular bolus only
• Oral gavage or diet incorporation
• Topical application to shaved skin only
• Intracerebral injection

Correct Answer: Oral gavage or diet incorporation

Q15. In interpreting biochemical data from sub-acute studies, which change would most specifically suggest cholestatic liver injury rather than hepatocellular injury?

• Marked elevation of ALT with normal alkaline phosphatase
• Prominent increase in alkaline phosphatase and bilirubin
• Elevated creatine kinase only
• Isolated hypoalbuminemia

Correct Answer: Prominent increase in alkaline phosphatase and bilirubin

Q16. Which concept describes the lowest dose that demonstrates statistically and biologically significant adverse effects compared with controls?

• NOAEL (No Observed Adverse Effect Level)
• LD50 (Lethal Dose 50%)
• LOAEL (Lowest Observed Adverse Effect Level)
• MTD (Maximum Tolerated Dose)

Correct Answer: LOAEL (Lowest Observed Adverse Effect Level)

Q17. Good Laboratory Practice (GLP) compliance in sub-acute toxicity studies primarily ensures that:

• All animals receive the same diet brand
• Study conduct, data collection, and reporting are reliable and auditable
• Only one pathologist evaluates all tissues
• The study is completed faster

Correct Answer: Study conduct, data collection, and reporting are reliable and auditable

Q18. Which statistical approach is most appropriate when comparing multiple dose groups to control for continuous endpoints in a sub-acute toxicity study?

• Descriptive statistics only, no comparisons
• Multiple t-tests without correction
• Analysis of variance (ANOVA) followed by post-hoc tests
• Kaplan–Meier survival analysis

Correct Answer: Analysis of variance (ANOVA) followed by post-hoc tests

Q19. A pronounced increase in relative liver weight without histopathological changes may indicate which of the following?

• Analytical assay failure
• Adaptive hypertrophy due to enzyme induction
• Primary cardiac toxicity
• Renal tubular atrophy

Correct Answer: Adaptive hypertrophy due to enzyme induction

Q20. When extrapolating a NOAEL from animals to humans to derive a safe starting dose in early clinical trials, which safety factor is commonly applied?

• No safety factor, direct mg/kg extrapolation
• 10-fold to account for interspecies differences and another 10-fold for human variability (total 100-fold)
• Only a 1.5-fold factor for metabolic rate
• Multiply animal NOAEL by body surface area without additional factors

Correct Answer: 10-fold to account for interspecies differences and another 10-fold for human variability (total 100-fold)

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