Developmental and teratogenicity studies (segment II) MCQs With Answer

Introduction: Developmental and teratogenicity studies (segment II) MCQs With Answer is a focused quiz resource designed for M.Pharm students preparing for pharmacology, toxicology and regulatory assessments. This set emphasizes embryo–fetal development testing performed during organogenesis, covering study design, species selection, dosing, endpoints, necropsy procedures, and regulatory expectations (e.g., OECD TG 414). Questions address practical laboratory techniques such as skeletal staining and visceral examination, interpretation of results (malformation vs variation, NOAEL), statistical considerations (litter as the experimental unit), and confounding factors like maternal toxicity. Use these MCQs to deepen conceptual understanding and reinforce applied knowledge required for conducting and interpreting Segment II developmental toxicity studies.

Q1. What is the primary objective of a Segment II developmental and teratogenicity study?

• To evaluate systemic toxicity in adult animals over 90 days
• To determine reproductive performance and fertility across two generations
• To detect adverse effects on embryo–fetal development and identify teratogenic potential during organogenesis
• To assess postnatal neurobehavioral development exclusively

Correct Answer: To detect adverse effects on embryo–fetal development and identify teratogenic potential during organogenesis

Q2. Which internationally accepted guideline specifically describes prenatal developmental toxicity study design commonly used for Segment II testing?

• OECD Test Guideline 408
• OECD Test Guideline 414
• ICH M3(R2)
• WHO GLP Guidelines

Correct Answer: OECD Test Guideline 414

Q3. Which pair of species is typically recommended for regulatory embryo–fetal development studies?

• Mouse and dog
• Rat and rabbit
• Guinea pig and non-human primate
• Hamster and cat

Correct Answer: Rat and rabbit

Q4. During which developmental window are test articles administered to assess teratogenic effects in Segment II studies?

• Pre-implantation period only
• Organogenesis period
• Perinatal lactation period
• Germ cell formation prior to mating

Correct Answer: Organogenesis period

Q5. Which staining technique is standard for visualization of fetal skeletal ossification in developmental toxicity studies?

• Hematoxylin and eosin staining of whole fetus
• Alizarin red S and Alcian blue double staining
• Gram staining of bone marrow
• Silver staining of neuronal tissue

Correct Answer: Alizarin red S and Alcian blue double staining

Q6. Which method is commonly used for detailed visceral (soft-tissue) examination of rodent fetuses?

• Wilson’s sectioning technique
• Alizarin red whole-mount technique
• Paraffin block decalcification technique only
• Freeze-fracture electron microscopy

Correct Answer: Wilson’s sectioning technique

Q7. A high number of implantation sites with few live fetuses and many early empty implantation scars indicates which reproductive effect?

• Post-implantation loss
• Pre-implantation loss
• Supernumerary fetal development
• Placental overgrowth

Correct Answer: Pre-implantation loss

Q8. For statistical analysis in prenatal developmental toxicity, which is considered the experimental unit for fetal endpoints to avoid pseudo-replication?

• Each individual fetus
• Each uterus
• The litter (one averaged value per litter)
• Each placenta separately

Correct Answer: The litter (one averaged value per litter)

Q9. How is a structural malformation distinguished from a developmental variation in fetal assessments?

• A malformation is a minor transient change; a variation always causes fetal death
• A malformation generally adversely affects fitness or survival, while a variation is a minor change without significant functional consequence
• Variations are only genetic and malformations are only teratogenic
• There is no practical difference; both terms are interchangeable

Correct Answer: A malformation generally adversely affects fitness or survival, while a variation is a minor change without significant functional consequence

Q10. In developmental toxicity studies, what does the developmental NOAEL represent?

• The lowest dose that causes maternal lethality
• The highest dose at which no adverse fetal or developmental effects are observed
• The dose that produces a 50% reduction in litter size
• The median effective dose for maternal toxicity

Correct Answer: The highest dose at which no adverse fetal or developmental effects are observed

Q11. If a compound’s teratogenic index (TI) indicates developmental effects at lower doses than those causing maternal toxicity, what does this imply?

• The compound is safe because maternal toxicity precedes fetal effects
• Developmental toxicity occurs at lower doses than maternal toxicity, suggesting specific embryofetal sensitivity
• TI has no interpretive value and should be ignored
• Maternal toxicity is solely responsible for fetal changes

Correct Answer: Developmental toxicity occurs at lower doses than maternal toxicity, suggesting specific embryofetal sensitivity

Q12. Which compound is commonly used as a positive control known to cause malformations in embryo–fetal development studies?

• All-trans retinoic acid
• Paracetamol
• Caffeine at nutritional doses
• Sucrose solution

Correct Answer: All-trans retinoic acid

Q13. For rats in a standard prenatal developmental toxicity study, on which gestation day is caesarean section/terminal necropsy commonly performed for fetal evaluation?

• Gestation day 10
• Gestation day 14
• Gestation day 20
• Postnatal day 7

Correct Answer: Gestation day 20

Q14. A pattern of delayed ossification in multiple fetal bones most likely indicates which outcome?

• Permanent malformation of skeletal elements
• Developmental retardation reflected by incomplete ossification
• Maternal bone disease transferred to fetus
• Infection-induced teratogenesis

Correct Answer: Developmental retardation reflected by incomplete ossification

Q15. If fetal abnormalities occur only at dose levels that also produce severe maternal toxicity, how should the fetal findings typically be interpreted?

• As definitive evidence of a primary teratogenic effect
• As likely secondary effects related to maternal toxicity rather than specific teratogenicity
• As unrelated to the test article
• As evidence that the test article is safe for developmental endpoints

Correct Answer: As likely secondary effects related to maternal toxicity rather than specific teratogenicity

Q16. Which maternal parameter is least commonly recorded as a routine mandatory variable in OECD TG 414 prenatal developmental toxicity studies?

• Maternal body weight and weight gain
• Food consumption
• Clinical signs and mortality
• Arterial blood pressure measurements

Correct Answer: Arterial blood pressure measurements

Q17. How is percent post‑implantation loss calculated in a prenatal developmental toxicity study?

• (Number of live fetuses / Number of implantation sites) × 100
• ((Number of implantation sites − Number of live fetuses) / Number of implantation sites) × 100
• (Number of resorptions / Number of live fetuses) × 100
• (Number of implantations / Number of corpora lutea) × 100

Correct Answer: ((Number of implantation sites − Number of live fetuses) / Number of implantation sites) × 100

Q18. Who is the most appropriate specialist to perform detailed evaluation and classification of fetal malformations and variations?

• Analytical chemist
• Teratologist or board-certified veterinary pathologist experienced in developmental pathology
• Laboratory animal caretaker with routine training
• Clinical pharmacist

Correct Answer: Teratologist or board-certified veterinary pathologist experienced in developmental pathology

Q19. Which approach is commonly used to assess placental transfer and fetal exposure to the test article in developmental toxicity studies?

• Measuring maternal urine output only
• Measurement of test article concentrations in fetal tissues and amniotic fluid (or autoradiography of radiolabelled compound)
• Behavioral testing of dams
• Counting implantation sites without chemical analysis

Correct Answer: Measurement of test article concentrations in fetal tissues and amniotic fluid (or autoradiography of radiolabelled compound)

Q20. What is the commonly recommended minimum number of pregnant females per dose group for rat studies under OECD TG 414 to ensure adequate statistical power?

• At least 5 pregnant females per group
• At least 10 pregnant females per group
• At least 20 pregnant females per group
• At least 50 pregnant females per group

Correct Answer: At least 20 pregnant females per group

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