Teratogenicity testing MCQs With Answer

Introduction

This quiz collection on teratogenicity testing is designed for M.Pharm students studying Biological Evaluation of Drug Therapy. It provides focused, exam-oriented multiple-choice questions covering core concepts: study designs, regulatory guidelines, species selection, critical gestational windows, endpoints, interpretation of data and mechanisms of teratogenesis. Questions emphasize practical aspects of prenatal developmental toxicity (OECD/ICH), differentiation between maternal toxicity and teratogenic effects, common positive controls, and modern in vitro approaches. Use these MCQs to reinforce understanding, prepare for viva/exams and apply knowledge when designing or assessing teratogenicity studies in drug development.

Q1. What is the primary purpose of a prenatal developmental toxicity (teratogenicity) study?

• To assess carcinogenic potential in offspring
• To evaluate effects of a substance on development of the embryo and fetus
• To determine only maternal pharmacokinetics
• To test acute toxicity in adult animals

Correct Answer: To evaluate effects of a substance on development of the embryo and fetus

Q2. Which guideline is most commonly referenced for conducting standard prenatal developmental toxicity studies in regulatory submissions?

• OECD TG 408
• OECD TG 414
• ICH Q3A
• ICH Q1A

Correct Answer: OECD TG 414

Q3. Which species pair is standardly recommended for teratogenicity testing to capture species-specific sensitivity?

• Mouse and dog
• Rat and rabbit
• Guinea pig and cat
• Hamster and primate

Correct Answer: Rat and rabbit

Q4. During which developmental period is organogenesis most sensitive to teratogenic insults in rodents?

• Pre-implantation period
• Peri-implantation period
• Organogenesis (approximately gestation days 6–15 in rats)
• Late fetal growth only

Correct Answer: Organogenesis (approximately gestation days 6–15 in rats)

Q5. Which finding in a developmental toxicity study is generally considered the most critical evidence of teratogenicity?

• Reduced maternal body weight gain
• Increased pre- and post-implantation loss
• Externally visible structural malformations in fetuses
• Minor variations in skeletal ossification

Correct Answer: Externally visible structural malformations in fetuses

Q6. What is the main reason to include a non-rodent species (commonly rabbit) in teratogenicity testing?

• Rabbits have identical drug metabolism to humans
• To increase sample size only
• To detect species-specific developmental responses that rodents might miss
• Because rabbits are cheaper than rodents

Correct Answer: To detect species-specific developmental responses that rodents might miss

Q7. Which of the following is a common positive control used in developmental toxicity assays for validating sensitivity?

• Acetaminophen
• Retinoic acid (all-trans-retinoic acid)
• Ibuprofen
• Sucrose

Correct Answer: Retinoic acid (all-trans-retinoic acid)

Q8. In differentiating maternal toxicity from direct embryofetal toxicity, which observation suggests a specific embryofetal effect rather than secondary to maternal harm?

• Fetal malformations only at doses that produce severe maternal morbidity
• Fetal effects observed at doses that cause no or minimal maternal toxicity
• Maternal body weight loss with no fetal changes
• Maternal lethality without fetal assessment

Correct Answer: Fetal effects observed at doses that cause no or minimal maternal toxicity

Q9. The Teratogenic Index (TI) is calculated as the ratio of which two values?

• NOAEL for maternal toxicity divided by NOAEL for fetus
• LD50 divided by NOAEL for maternal toxicity
• LD50 divided by ED50
• LD50 for maternal animals divided by ED50 for teratogenic effect

Correct Answer: LD50 for maternal animals divided by ED50 for teratogenic effect

Q10. Which developmental endpoint is typically evaluated to detect delayed skeletal development?

• External gross malformations only
• Skeletal ossification scoring in cleared and stained fetuses
• Maternal organ weight measurement
• Placental histology only

Correct Answer: Skeletal ossification scoring in cleared and stained fetuses

Q11. Which guideline addresses assessment of reproductive and developmental toxicity including screening studies (e.g., combined reproduction/developmental screening)?

• OECD TG 420
• OECD TG 421/422
• ICH M4
• ISO 10993

Correct Answer: OECD TG 421/422

Q12. Which mechanism is associated with valproic acid’s teratogenicity?

• Folate antagonism and histone deacetylase inhibition
• Direct placental mechanical disruption
• Protein aggregation in maternal liver only
• Calcium channel blockade in fetus

Correct Answer: Folate antagonism and histone deacetylase inhibition

Q13. Whole embryo culture and zebrafish embryo assays are examples of what category of teratogenicity testing?

• Clinical human trials
• In vivo multigeneration studies
• In vitro or alternative models for early developmental screening
• Post-marketing surveillance

Correct Answer: In vitro or alternative models for early developmental screening

Q14. Which maternal parameter must be monitored closely and reported because it can confound interpretation of fetal effects?

• Maternal fur color
• Maternal body weight gain and food consumption
• Number of cage mates
• Offspring grooming behavior

Correct Answer: Maternal body weight gain and food consumption

Q15. Which statement about thalidomide illustrates a key principle in teratogenicity testing?

• All species show identical sensitivity, so one species suffices
• Species-specific differences can mask human risk; testing multiple species is important
• Teratogenicity depends solely on administered dose, not metabolism
• Teratogens are always detected by routine genotoxicity tests

Correct Answer: Species-specific differences can mask human risk; testing multiple species is important

Q16. In OECD TG 414, which fetal observations are classified as “variations” rather than malformations?

• Severe structural defects incompatible with life
• Minor deviations in anatomical development considered to have no major functional consequence
• Major organ agenesis
• External limb duplications

Correct Answer: Minor deviations in anatomical development considered to have no major functional consequence

Q17. Which pharmacokinetic factor most directly affects whether a compound can reach the embryo/fetus and exert teratogenic effects?

• Protein binding in adult muscle only
• Ability to cross the placenta and fetal exposure levels
• Skin absorption in the dam
• Renal excretion in male animals

Correct Answer: Ability to cross the placenta and fetal exposure levels

Q18. For regulatory decision-making, what is the primary significance of identifying a NOAEL in developmental toxicity studies?

• To establish a safe human therapeutic index and margin of safety for developmental risk assessment
• To determine cosmetic labeling only
• To replace clinical pregnancy testing
• To set environmental discharge limits

Correct Answer: To establish a safe human therapeutic index and margin of safety for developmental risk assessment

Q19. Which of the following is an appropriate approach when fetal malformations occur only at maternally toxic doses?

• Conclude unequivocally that the compound is teratogenic in humans
• Investigate whether fetal effects are secondary to maternal toxicity and consider dose spacing or mechanistic studies
• Ignore the findings since maternal toxicity explains everything
• Stop all further testing immediately

Correct Answer: Investigate whether fetal effects are secondary to maternal toxicity and consider dose spacing or mechanistic studies

Q20. Which postnatal study is most informative for assessing functional and behavioral consequences of prenatal exposure?

• Embryo culture assay
• Pre- and post-natal development (PPND) study with offspring followed to maturity
• Acute oral toxicity test in adults
• OECD aquatic toxicity test

Correct Answer: Pre- and post-natal development (PPND) study with offspring followed to maturity

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