Regulatory guidelines for toxicity studies: OECD, ICH, EPA, Schedule Y MCQs With Answer

Introduction:

Regulatory guidelines for toxicity studies are essential for M.Pharm students to understand how nonclinical safety data are generated, interpreted, and accepted by authorities worldwide. This blog focuses on core frameworks—OECD test guidelines and GLP principles, ICH safety guidance (including M and S series), EPA toxicology standards, and India’s Schedule Y—highlighting study types, data expectations, and regulatory intent. The goal is to strengthen your ability to design toxicity studies, choose appropriate guideline endpoints, and know what regulators expect for clinical trial authorization and marketing. The following MCQs with answers will test and deepen your knowledge of practical and regulatory aspects of safety assessment.

Q1. Which OECD Test Guidelines are most commonly referenced for acute oral toxicity testing in regulatory submissions?

• OECD TG 420, 423 and 425
• OECD TG 407 and 408
• OECD TG 471 and 473
• OECD TG 414 and 416

Correct Answer: OECD TG 420, 423 and 425

Q2. Which ICH guideline primarily addresses the nonclinical safety studies needed to support the conduct of clinical trials in humans?

• ICH M3(R2)
• ICH S1
• ICH Q1A
• ICH S7A

Correct Answer: ICH M3(R2)

Q3. According to OECD principles, what is the central purpose of Good Laboratory Practice (GLP)?

• To ensure the quality, integrity and reliability of nonclinical safety data
• To define clinical trial conduct and patient safety measures
• To standardize marketing and labeling of pharmaceuticals
• To set acceptable human dose ranges for first-in-human studies

Correct Answer: To ensure the quality, integrity and reliability of nonclinical safety data

Q4. Which OECD Test Guideline is commonly used for 90-day repeated dose oral toxicity studies in rodents?

• OECD TG 408
• OECD TG 407
• OECD TG 413
• OECD TG 420

Correct Answer: OECD TG 408

Q5. ICH S2(R1) guidance focuses on which area of nonclinical testing?

• Genotoxicity testing strategies and interpretation
• Carcinogenicity study design and requirements
• Reproductive and developmental toxicity testing
• Safety pharmacology core battery

Correct Answer: Genotoxicity testing strategies and interpretation

Q6. The EPA toxicology guidelines are often grouped under which series and are important for chemical risk assessment?

• OPPTS/870 series for health effects
• ICH M series for nonclinical safety
• OECD GLP series for study conduct
• Schedule Y annexes for clinical trials

Correct Answer: OPPTS/870 series for health effects

Q7. Which OECD Test Guideline is used for the bacterial reverse mutation (Ames) test?

• OECD TG 471
• OECD TG 474
• OECD TG 476
• OECD TG 408

Correct Answer: OECD TG 471

Q8. For first-in-human (FIH) clinical trials, Schedule Y in India expects nonclinical data including:

• Single-dose toxicity, repeated-dose toxicity, genotoxicity and safety pharmacology as applicable
• Only pharmacokinetic data in humans
• Full lifetime carcinogenicity studies for all new drugs
• No animal data are required if in vitro tests are done

Correct Answer: Single-dose toxicity, repeated-dose toxicity, genotoxicity and safety pharmacology as applicable

Q9. Which ICH guideline series specifically addresses reproductive and developmental toxicology?

• ICH S5
• ICH S1
• ICH M3(R2)
• ICH Q3

Correct Answer: ICH S5

Q10. OECD TG 474 refers to which genotoxicity endpoint?

• Mammalian erythrocyte micronucleus test (in vivo)
• Bacterial reverse mutation test (Ames)
• In vitro mammalian cell gene mutation
• Prenatal developmental toxicity

Correct Answer: Mammalian erythrocyte micronucleus test (in vivo)

Q11. Under ICH M3(R2), what is a major consideration when deciding the duration of repeated-dose toxicity studies before initiating Phase III clinical trials?

• The clinical trial duration and intended exposure in humans
• The manufacturing process validation status
• The drug’s color and formulation excipients
• The number of investigators participating in the trial

Correct Answer: The clinical trial duration and intended exposure in humans

Q12. Which of the following is a key difference between OECD and EPA regulatory frameworks for toxicity testing?

• OECD provides internationally harmonized Test Guidelines and GLP principles, while EPA provides region-specific test rule sets and risk assessment guidance
• OECD dictates clinical trial design, while EPA regulates drug pricing
• OECD applies only to pesticides, EPA applies only to pharmaceuticals
• OECD enforces human trials, EPA enforces animal welfare only

Correct Answer: OECD provides internationally harmonized Test Guidelines and GLP principles, while EPA provides region-specific test rule sets and risk assessment guidance

Q13. Which study is normally required to assess the potential of a drug to cause structural or functional birth defects?

• Prenatal developmental toxicity study (e.g., OECD TG 414)
• 90-day subchronic toxicity in rats (OECD TG 408)
• Ames bacterial mutation test (OECD TG 471)
• Dermal irritation test (OECD TG 404)

Correct Answer: Prenatal developmental toxicity study (e.g., OECD TG 414)

Q14. Which ICH guideline describes core safety pharmacology studies intended to identify potential undesirable pharmacodynamic effects on vital organ systems?

• ICH S7A
• ICH S1
• ICH Q5C
• ICH M3(R2)

Correct Answer: ICH S7A

Q15. In regulatory toxicology, what is the primary objective of a limit dose approach in acute toxicity testing?

• To reduce animal use by testing a single high dose that, if non-lethal, negates need for further dose-range finding
• To determine the exact LD50 value for labeling
• To replace genotoxicity tests for regulatory submission
• To assess chronic toxicity over lifetime exposure

Correct Answer: To reduce animal use by testing a single high dose that, if non-lethal, negates need for further dose-range finding

Q16. Under Schedule Y, what additional nonclinical data may be requested for a biological (biotech) product beyond standard small molecule requirements?

• Immunogenicity assessment and specific toxicology in relevant species
• Only Ames test and dermal irritation studies
• No toxicology is required if the active is a protein
• Human efficacy data prior to Phase I

Correct Answer: Immunogenicity assessment and specific toxicology in relevant species

Q17. The OECD Principles of GLP require which of the following as a standard practice in study conduct?

• Traceable documentation of study plan, raw data, and final report
• Publication of results in at least two peer-reviewed journals
• Use of only one animal species for all studies
• Conducting all tests without laboratory controls

Correct Answer: Traceable documentation of study plan, raw data, and final report

Q18. Which ICH document would you consult to determine nonclinical carcinogenicity testing strategy for a small molecule intended for chronic human use?

• ICH S1
• ICH S7A
• ICH Q1A
• ICH E6

Correct Answer: ICH S1

Q19. In EPA hazard assessment, what is a primary use of data from standard OECD genotoxicity and chronic studies?

• To support human health risk characterization and set exposure limits
• To determine clinical dosing regimens for Phase II trials
• To replace GLP requirements in documentation
• To set manufacturing batch release criteria

Correct Answer: To support human health risk characterization and set exposure limits

Q20. Which of the following best describes the role of OECD Test Guidelines in global regulatory submissions?

• They provide harmonized, science-based procedures for conducting toxicity tests acceptable across many regulatory authorities
• They mandate clinical trial protocols and patient recruitment procedures
• They only apply to cosmetic ingredient testing and are not relevant to drugs
• They set pricing and reimbursement policies for new medicines

Correct Answer: They provide harmonized, science-based procedures for conducting toxicity tests acceptable across many regulatory authorities

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