ABT Reproductive and Developmental Toxicology 2 — Questions and Answers
Question 1: ICH S5(R3) guidelines govern which aspect of pharmaceutical development?
- Genotoxicity testing
- Detection of reproductive and developmental toxicity for human pharmaceuticals (Correct answer)
- Carcinogenicity studies
- Acute toxicity study design
Correct answer: Detection of reproductive and developmental toxicity for human pharmaceuticals
ICH S5(R3) provides internationally harmonized guidelines for reproductive and developmental toxicology studies (fertility, embryo-fetal development, pre-/postnatal development) for drug registration.
Question 2: A 'developmental NOAEL' is used in risk assessment to protect against which type of toxic effect?
- Maternal mortality from high-dose exposure
- Adverse effects on the developing organism (structural, functional, or growth-related) (Correct answer)
- Carcinogenicity in offspring
- Mutagenicity in germline cells
Correct answer: Adverse effects on the developing organism (structural, functional, or growth-related)
The developmental NOAEL is the highest dose causing no adverse developmental effects (structural malformations, growth restriction, functional deficits) and is used to set human safety limits.
Question 3: Alcohol is a well-established human teratogen. The most severe outcome of prenatal alcohol exposure is:
- Fetal alcohol spectrum disorder (FASD) — neurobehavioral effects only
- Fetal alcohol syndrome (FAS) — growth restriction, CNS abnormalities, and facial dysmorphology (Correct answer)
- Neonatal abstinence syndrome
- Neural tube defects only
Correct answer: Fetal alcohol syndrome (FAS) — growth restriction, CNS abnormalities, and facial dysmorphology
Fetal alcohol syndrome (FAS) is the most severe outcome of prenatal alcohol exposure and is characterized by growth restriction, central nervous system damage, and a characteristic facial phenotype.
Question 4: Which test in the developmental toxicity battery specifically evaluates learning and memory deficits caused by in utero chemical exposure?
- Teratology study (Segment II)
- Developmental neurotoxicity (DNT) study (Correct answer)
- Two-generation reproductive study
- Epigenetic methylation assay
Correct answer: Developmental neurotoxicity (DNT) study
The developmental neurotoxicity (DNT) study, guided by OECD 426 and EPA DNT guidelines, assesses functional CNS endpoints including motor activity, learning, memory, and sensory function in offspring.
Question 5: Which male reproductive toxicant causes depletion of spermatogonia by alkylating DNA in the seminiferous epithelium?
- Bisphenol A (BPA)
- Dibromochloropropane (DBCP) (Correct answer)
- Phthalates (DEHP)
- Vinclozolin
Correct answer: Dibromochloropropane (DBCP)
DBCP (dibromochloropropane) is a nematocide that caused permanent infertility in male workers by alkylating and destroying spermatogonial stem cells in the seminiferous epithelium.
Question 6: Valproic acid is a potent human teratogen that primarily causes which neural tube defect when taken in the first trimester?
- Anencephaly
- Spina bifida (myelomeningocele) (Correct answer)
- Holoprosencephaly
- Dandy-Walker malformation
Correct answer: Spina bifida (myelomeningocele)
Valproic acid causes spina bifida (myelomeningocele) by inhibiting folate metabolism and histone deacetylase, disrupting neural tube closure during weeks 3–4 of gestation.
ABT Reproductive and Developmental Toxicology 2
ICH S5(R3) guidelines govern which aspect of pharmaceutical development?