Toxicity tests: chronic MCQs With Answer

Toxicity tests: chronic MCQs With Answer — Introduction

Chronic toxicity testing is a cornerstone of preclinical safety evaluation, assessing the effects of repeated or continuous exposure to a drug over extended periods. For M.Pharm students, mastering chronic toxicity concepts—study design, selection of species, dose levels, endpoints such as clinical pathology and histopathology, interpretation of NOAEL/LOAEL, and regulatory expectations—is essential for designing and interpreting long-term safety studies. This quiz collection focuses on deeper, practical aspects of chronic toxicity testing used in drug development, reinforcing regulatory principles, study rationale, and common pitfalls encountered when translating animal toxicity findings to human risk assessment.

Q1. What is the primary objective of chronic toxicity studies in drug development?

• To determine acute lethal dose after single exposure
• To assess allergic reactions only
• To evaluate the adverse effects of repeated exposure over an extended period, identify target organs, and establish dose–response relationships including NOAEL
• To measure pharmacodynamic efficacy in animal disease models

Correct Answer: To evaluate the adverse effects of repeated exposure over an extended period, identify target organs, and establish dose–response relationships including NOAEL

Q2. Which species selection is commonly recommended for chronic toxicity programs supporting long-term clinical use?

• Only a single rodent species regardless of drug class
• One rodent and one non-rodent species, chosen for pharmacological relevance and metabolic similarity
• Only non-mammalian species such as fish
• Any available laboratory strain without justification

Correct Answer: One rodent and one non-rodent species, chosen for pharmacological relevance and metabolic similarity

Q3. What does NOAEL stand for in chronic toxicity studies?

• New Observed Adverse Effect Level
• Non-Observed Adverse Effect Limit
• Number of Animals Exposed at Level
• No Observed Adverse Effect Level

Correct Answer: No Observed Adverse Effect Level

Q4. LOAEL is defined as which of the following?

• The highest dose that produces no effect
• The lowest dose at which adverse effects are observed
• The dose that causes lethality in 50% of animals
• The median effective pharmacological dose

Correct Answer: The lowest dose at which adverse effects are observed

Q5. How do chronic toxicity studies differ from carcinogenicity studies?

• Chronic toxicity studies assess general systemic toxicity from long-term exposure; carcinogenicity studies specifically evaluate tumor incidence and neoplastic potential
• They are identical; both always use lifespan exposure in rodents
• Chronic toxicity focuses only on reproductive endpoints while carcinogenicity focuses on liver toxicity
• Carcinogenicity studies do not require histopathology

Correct Answer: Chronic toxicity studies assess general systemic toxicity from long-term exposure; carcinogenicity studies specifically evaluate tumor incidence and neoplastic potential

Q6. What is the main purpose of including a satellite recovery group in a chronic toxicity study?

• To increase statistical power for tumor incidence
• To assess reversibility, persistence, or delayed appearance of toxic effects after cessation of dosing
• To serve as an untreated control group
• To test different routes of administration in the same study

Correct Answer: To assess reversibility, persistence, or delayed appearance of toxic effects after cessation of dosing

Q7. Which set of endpoints is typically evaluated in chronic toxicity studies?

• Only survival and behavior
• Clinical signs, body weight, food consumption, clinical pathology, organ weights, and histopathology
• Only genotoxicity endpoints
• Only pharmacokinetic parameters without pathology

Correct Answer: Clinical signs, body weight, food consumption, clinical pathology, organ weights, and histopathology

Q8. The route of administration chosen for chronic toxicity studies should normally be:

• The route easiest for the laboratory technicians
• A route unrelated to the intended human route
• The intended clinical route or one that provides comparable systemic exposure
• Always intravenous regardless of human use

Correct Answer: The intended clinical route or one that provides comparable systemic exposure

Q9. What principle guides the selection of dose levels for chronic toxicity studies?

• Only one very high dose should be used
• Include a control and at least three dose levels (low, mid, high) so the high dose elicits toxicity but not excessive mortality
• Use doses lower than expected human exposure exclusively
• Random dose selection to avoid bias

Correct Answer: Include a control and at least three dose levels (low, mid, high) so the high dose elicits toxicity but not excessive mortality

Q10. How is the Maximum Tolerated Dose (MTD) best described?

• The lowest dose that produces no therapeutic effect
• The dose that causes immediate death in all animals
• The highest dose that can be given repeatedly that produces defined toxicity but not unacceptable mortality
• A dose selected to produce only mild, reversible effects

Correct Answer: The highest dose that can be given repeatedly that produces defined toxicity but not unacceptable mortality

Q11. Why is histopathology central to chronic toxicity evaluation?

• Because gross observations are sufficient without it
• It detects microscopic tissue and cellular changes that reveal target organ toxicity and mechanisms of injury
• It replaces clinical chemistry entirely
• Only to confirm animal identity

Correct Answer: It detects microscopic tissue and cellular changes that reveal target organ toxicity and mechanisms of injury

Q12. Role of toxicokinetics in chronic toxicity studies includes which of the following?

• To determine if systemic exposure at the selected doses is relevant to humans and to interpret dose–response relationships
• To replace histopathology
• Only to measure urine output
• To increase animal numbers unnecessarily

Correct Answer: To determine if systemic exposure at the selected doses is relevant to humans and to interpret dose–response relationships

Q13. Which regulatory expectation often applies before initiating long-term clinical use of a new pharmaceutical?

• No animal data are required if in-vitro tests look safe
• Chronic toxicity data in at least one species only
• Data from appropriate repeated-dose toxicity studies, typically including chronic studies in rodent and non-rodent species, are expected to support long-term human exposure
• Only human volunteer data are required

Correct Answer: Data from appropriate repeated-dose toxicity studies, typically including chronic studies in rodent and non-rodent species, are expected to support long-term human exposure

Q14. Which statistical consideration is most important in chronic toxicity studies?

• Use of descriptive statistics only with no hypothesis testing
• Appropriate statistical tests for continuous and categorical data and consideration of sex, litter effects, and multiple comparisons
• Ignoring variability to simplify reporting
• Relying solely on p-values below 0.01 without biological context

Correct Answer: Appropriate statistical tests for continuous and categorical data and consideration of sex, litter effects, and multiple comparisons

Q15. Which finding would most strongly suggest a direct test article–related kidney effect in a chronic study?

• Transient change in hair color with no organ pathology
• Increased serum creatinine, histopathological lesions in renal tubules, and dose-related changes in kidney weight
• Unrelated behavioral changes without clinical pathology
• Reduced food intake with no kidney lesions

Correct Answer: Increased serum creatinine, histopathological lesions in renal tubules, and dose-related changes in kidney weight

Q16. Which statement about reversibility of toxic effects is correct?

• All chronic toxic effects are irreversible once observed
• Reversibility can only be evaluated in in-vitro tests
• Recovery groups are used to determine whether observed effects reverse after dosing stops, indicating reversibility or persistence
• Reversibility is inferred solely from body weight changes

Correct Answer: Recovery groups are used to determine whether observed effects reverse after dosing stops, indicating reversibility or persistence

Q17. Standard rodent carcinogenicity study duration is typically:

• 1–3 weeks
• 6 months
• 18–24 months to assess tumor incidence over the lifespan
• Only until the first tumor appears

Correct Answer: 18–24 months to assess tumor incidence over the lifespan

Q18. Which combination most reliably indicates organ-specific chronic toxicity?

• Single transient abnormal clinical sign
• Dose-related biochemical abnormality plus corroborative histopathology and organ weight change
• Random fluctuations in body weight only
• Isolated clinical chemistry change without pathological correlation

Correct Answer: Dose-related biochemical abnormality plus corroborative histopathology and organ weight change

Q19. Under what quality framework are regulatory chronic toxicity studies usually conducted?

• No specific quality framework is required
• Under Good Laboratory Practice (GLP) to ensure reliable and auditable data
• Only under ISO clinical trial standards
• Under pharmacopoeial compendia only

Correct Answer: Under Good Laboratory Practice (GLP) to ensure reliable and auditable data

Q20. When is juvenile chronic toxicity testing specifically required?

• Never required for pediatric drug development
• When the drug is intended for prolonged use in pediatric populations to assess age-related sensitivity and organ development effects
• Only for topical products
• Only if adult toxicity is absent

Correct Answer: When the drug is intended for prolonged use in pediatric populations to assess age-related sensitivity and organ development effects

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