Understanding acute, subacute, and chronic toxicity is essential for B.Pharm students involved in drug development, safety pharmacology, and toxicology. Acute toxicity refers to adverse effects after a single or short-term exposure, subacute (repeated exposure up to 28 days) identifies intermediate hazards, and chronic toxicity stems from long-term exposure producing cumulative organ damage, carcinogenicity, or reproductive effects. Key concepts include dose-response relationships, LD50, NOAEL, LOAEL, toxicokinetics, target organ toxicity, bioaccumulation, and regulatory tests (e.g., OECD 407, 408). Mastery of these topics helps interpret preclinical studies, design safer dosing regimens, and perform risk assessment. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which definition best describes acute toxicity?
- Adverse effects from repeated exposure over months to years
- Adverse effects after a single or short-term exposure, usually within 24–96 hours
- Adverse effects from exposure for exactly 28 days
- Only genetic and reproductive adverse effects
Correct Answer: Adverse effects after a single or short-term exposure, usually within 24–96 hours
Q2. Subacute toxicity studies commonly evaluate effects over which period?
- Single dose with 14-day observation
- Repeated dosing up to 28 days
- Exposure for two years
- Seven days continuous exposure only
Correct Answer: Repeated dosing up to 28 days
Q3. Chronic toxicity typically assesses which of the following endpoints?
- Immediate allergic reactions only
- Long-term organ damage, carcinogenicity, and reproductive effects
- Only pharmacokinetic parameters in plasma
- Acute behavioral changes within hours
Correct Answer: Long-term organ damage, carcinogenicity, and reproductive effects
Q4. LD50 is best described as:
- The dose causing 50% of animals to display liver enzyme changes
- The dose lethal to 50% of a test population
- The dose with no observed adverse effect level
- The maximum tolerated dose for humans
Correct Answer: The dose lethal to 50% of a test population
Q5. NOAEL stands for:
- No observed adverse effect level
- New observed acute effect limit
- Normal organ activity evaluation level
- Not observed as effect level
Correct Answer: No observed adverse effect level
Q6. Which OECD guideline corresponds to a 90-day repeated dose toxicity study in rodents?
- OECD 407
- OECD 408
- OECD 410
- OECD 420
Correct Answer: OECD 408
Q7. A primary aim of subchronic toxicity studies is to:
- Identify immediate pharmacodynamic effects only
- Determine cumulative toxicity, target organs, and NOAEL for longer-term risk assessment
- Replace all chronic human studies
- Measure only LD50 values
Correct Answer: Determine cumulative toxicity, target organs, and NOAEL for longer-term risk assessment
Q8. Which biomarker is most commonly used to assess hepatotoxicity in toxicity studies?
- Serum creatinine
- ALT (alanine aminotransferase)
- Serum amylase
- Hemoglobin concentration
Correct Answer: ALT (alanine aminotransferase)
Q9. LOAEL refers to:
- Lowest observed adverse effect level
- Limit of acceptable exposure limit
- Lowest observed acute effect limit
- Level of optimal absorption and elimination
Correct Answer: Lowest observed adverse effect level
Q10. Which parameter best indicates renal injury in preclinical studies?
- Increased ALT
- Decreased blood glucose
- Elevated blood urea nitrogen (BUN) and serum creatinine
- Red cell distribution width
Correct Answer: Elevated blood urea nitrogen (BUN) and serum creatinine
Q11. The main difference between subacute and subchronic toxicity is:
- Subacute is single dose, subchronic is multi-dose
- Subacute covers up to 28 days, subchronic generally covers 90 days
- Subacute studies are only in vitro
- There is no difference; terms are interchangeable
Correct Answer: Subacute covers up to 28 days, subchronic generally covers 90 days
Q12. Which study is most appropriate to identify carcinogenic potential?
- Single-dose acute toxicity test
- Short-term in vitro cytotoxicity test
- Two-year chronic bioassay in rodents
- 28-day subacute study only
Correct Answer: Two-year chronic bioassay in rodents
Q13. Bioaccumulation increases risk primarily because:
- It enhances renal clearance
- Repeated exposures lead to higher tissue concentrations over time
- It reduces drug absorption
- It prevents protein binding
Correct Answer: Repeated exposures lead to higher tissue concentrations over time
Q14. Which is a key toxicokinetic factor affecting toxicity?
- Color of compound
- Absorption, distribution, metabolism, and excretion (ADME)
- The company manufacturing the drug
- Packaging material
Correct Answer: Absorption, distribution, metabolism, and excretion (ADME)
Q15. Idiosyncratic drug reactions are best described as:
- Predictable dose-related effects seen in all animals
- Unpredictable reactions not clearly dose-related and often immune-mediated
- Only seen in in vitro assays
- Always reversible within hours
Correct Answer: Unpredictable reactions not clearly dose-related and often immune-mediated
Q16. Which endpoint is commonly monitored as a nonspecific indicator of systemic toxicity?
- Body weight changes
- Heart rate only during dosing
- Color of the formulation
- Packaging integrity
Correct Answer: Body weight changes
Q17. Margin of safety in toxicity assessment is best defined as:
- The therapeutic index multiplied by 100
- The ratio between toxic dose (e.g., NOAEL) and expected human exposure
- The LD50 value expressed in mg/kg only
- The number of animals surviving a study
Correct Answer: The ratio between toxic dose (e.g., NOAEL) and expected human exposure
Q18. Which organ is commonly the primary target for repeated-dose toxicity of many xenobiotics?
- Lens of the eye
- Liver
- Toenails
- Adipose tissue only
Correct Answer: Liver
Q19. Which assay is most relevant for detecting genotoxic potential?
- Ames test for bacterial reverse mutation
- 28-day neurobehavioral screen
- Serum ALT measurement
- Blood pressure monitoring
Correct Answer: Ames test for bacterial reverse mutation
Q20. Maximum tolerated dose (MTD) in toxicity studies is chosen to:
- Be the dose with zero observable effects
- Cause minimal lethality but produce clear toxicity without excessive suffering
- Always equal the human therapeutic dose
- Ensure all animals survive without any clinical signs
Correct Answer: Cause minimal lethality but produce clear toxicity without excessive suffering
Q21. Reproductive and developmental toxicity testing is primarily designed to detect:
- Changes in blood electrolytes only
- Teratogenicity, fertility effects, and peri-/post-natal development issues
- Acute skin irritation
- Immediate respiratory effects
Correct Answer: Teratogenicity, fertility effects, and peri-/post-natal development issues
Q22. A steep dose-response curve indicates:
- Small changes in dose produce large changes in effect
- Dose has no effect on response
- Only chronic toxicity is possible
- The drug is non-toxic at any dose
Correct Answer: Small changes in dose produce large changes in effect
Q23. Which factor increases susceptibility to chronic toxicity?
- Efficient rapid elimination of the compound
- High fat solubility and slow metabolic clearance
- Very high protein binding preventing tissue distribution
- Exclusive topical use with no systemic absorption
Correct Answer: High fat solubility and slow metabolic clearance
Q24. In repeat-dose toxicity studies, histopathology is performed to:
- Assess gross morphology only
- Identify cellular and tissue-level target organ lesions
- Measure compound concentration in plasma
- Determine animal behavior changes
Correct Answer: Identify cellular and tissue-level target organ lesions
Q25. Which regulatory concept uses NOAEL to estimate safe human exposure?
- Therapeutic index calculation only
- Applying uncertainty or safety factors to derive human acceptable daily intake (ADI)
- LD50 conversion to human dose directly
- Choosing the highest animal dose as human dose
Correct Answer: Applying uncertainty or safety factors to derive human acceptable daily intake (ADI)
Q26. Which route of exposure is most affected by first-pass metabolism and may reduce systemic toxicity?
- Intravenous
- Oral
- Inhalation
- Topical dermal with no absorption
Correct Answer: Oral
Q27. Repeated-dose inhalation toxicity studies report LOAEC. What does LOAEC mean?
- Lowest observed adverse effect concentration
- Limit of acceptable exposure cutoff
- Lowest observed acute exposure content
- Level of air contamination
Correct Answer: Lowest observed adverse effect concentration
Q28. Which is a common hematological change indicating bone marrow toxicity?
- Elevated ALT
- Leukopenia or anemia
- Hyperglycemia
- Increased creatinine clearance
Correct Answer: Leukopenia or anemia
Q29. Safety pharmacology core battery typically assesses effects on:
- Cardiovascular, respiratory, and central nervous systems
- Only liver metabolism
- Genotoxicity endpoints
- Color and odor of test article
Correct Answer: Cardiovascular, respiratory, and central nervous systems
Q30. When selecting animal species for chronic toxicity studies, a key consideration is:
- Similarity in metabolism and target organ sensitivity to humans
- Availability of the cheapest animals regardless of biology
- Only the size of the animal
- Using species that do not tolerate the compound
Correct Answer: Similarity in metabolism and target organ sensitivity to humans
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