Rationale for species and sex selection in studies MCQs With Answer

Introduction

This quiz set focuses on the rationale for selecting species and sex in preclinical pharmacological and toxicological studies — a critical component of M.Pharm training. It explains why particular animals (rodents, non-rodents) and sexes are chosen based on physiology, metabolism, reproduction, and regulatory expectations. The questions probe differences in ADME, enzyme expression, placental transfer, disease models, and translational predictability, as well as ethical, logistical and statistical considerations. These MCQs will help students consolidate principles behind species/sex choice, design robust studies, anticipate sex-specific effects, and understand guidance from agencies such as ICH and OECD, improving experimental design and interpretation.

Q1. Which primary factor most commonly drives the initial choice of a rodent species for general pharmacology screening?

• Presence of drug-specific target identical to humans
• Lower cost and ease of handling
• Regulatory requirement for rodent use
• Long lifespan for chronic studies

Correct Answer: Lower cost and ease of handling

Q2. For pivotal toxicology studies supporting human safety, regulators typically require data from both a rodent and a non-rodent species because:

• Non-rodents are always more predictive of human response
• Combining species doubles statistical power
• Different species cover diverse metabolic and physiological profiles
• Rodents lack critical organ systems present in non-rodents

Correct Answer: Different species cover diverse metabolic and physiological profiles

Q3. Which of the following is the strongest justification to select a non-human primate (NHP) for preclinical studies?

• Lower maintenance cost compared with dogs
• Presence of the target receptor with human-like binding and downstream signaling
• Faster breeding cycle for colony expansion
• Better tolerance to high doses

Correct Answer: Presence of the target receptor with human-like binding and downstream signaling

Q4. Why is sex-balanced inclusion increasingly emphasized in preclinical pharmacology studies?

• Male animals are typically more variable, so including females reduces variability
• To detect sex-specific pharmacodynamics and pharmacokinetics that affect translation to humans
• Regulatory agencies prohibit single-sex studies
• Females are cheaper to house and less aggressive

Correct Answer: To detect sex-specific pharmacodynamics and pharmacokinetics that affect translation to humans

Q5. Which physiological difference between male and female animals often affects drug clearance?

• Differences in fur color
• Sex-specific expression of drug-metabolizing enzymes (e.g., CYP isoforms)
• Number of limbs
• Dietary preferences

Correct Answer: Sex-specific expression of drug-metabolizing enzymes (e.g., CYP isoforms)

Q6. When evaluating reproductive toxicity and placental transfer potential, which species is commonly preferred for embryo-fetal development studies?

• Mouse for all cases because of rapid gestation
• Rabbit, because its placentation and fetal sensitivity provide relevant information
• Rat exclusively, since they are smallest
• Dog for embryo-fetal studies due to litter size

Correct Answer: Rabbit, because its placentation and fetal sensitivity provide relevant information

Q7. A major disadvantage of using non-human primates in routine toxicology is:

• They have identical ADME to humans, leading to redundant data
• High ethical concerns, cost, and limited availability
• Short lifespan preventing chronic studies
• Complete resistance to many xenobiotics

Correct Answer: High ethical concerns, cost, and limited availability

Q8. Which statement best explains why dogs are often selected as the non-rodent species in toxicity testing?

• Dogs metabolize all drugs exactly like humans
• Dogs have a size and physiology convenient for repeated dosing and clinical pathology sampling
• They are impervious to gastrointestinal adverse effects
• They breed as rapidly as rodents

Correct Answer: Dogs have a size and physiology convenient for repeated dosing and clinical pathology sampling

Q9. Which regulatory guidance specifically recommends consideration of both sexes in nonclinical studies when justified?

• ICH S6 only
• OECD acute toxicity test guidelines
• ICH M3(R2) and related ICH guidances encouraging sex-specific data where relevant
• None — regulators prefer single-sex studies

Correct Answer: ICH M3(R2) and related ICH guidances encouraging sex-specific data where relevant

Q10. In pharmacokinetic bridging studies, the primary reason to include both sexes is to:

• Ensure equal numbers of animals are used across studies
• Detect sex-related differences in absorption, distribution, metabolism, and excretion
• Reduce the number of analytical samples
• Increase drug exposure uniformly

Correct Answer: Detect sex-related differences in absorption, distribution, metabolism, and excretion

Q11. Which of the following is a scientific reason to avoid using pregnant females in general toxicology screens?

• Pregnancy alters physiology and can confound interpretation of maternal toxicity versus developmental effects
• Pregnant animals have lower body weights making dosing difficult
• Regulators prohibit any use of pregnant animals
• Pregnant animals are cheaper to maintain

Correct Answer: Pregnancy alters physiology and can confound interpretation of maternal toxicity versus developmental effects

Q12. Translatability from animal models to humans is improved when the selected species has:

• Identical diet to humans
• Similar target expression, pharmacology, and metabolic pathways to humans
• Smaller size for ease of handling
• Higher reproductive rate

Correct Answer: Similar target expression, pharmacology, and metabolic pathways to humans

Q13. Which factor is least relevant when choosing the sex of animals for a mechanistic PD study of a drug targeting male-specific pathways?

• Presence of the male-specific pathway or receptor
• Sex hormone milieu influencing target activity
• Need to detect female-specific off-target effects
• Costs associated with maintaining both sexes

Correct Answer: Need to detect female-specific off-target effects

Q14. When might a single-sex study (only males or only females) be considered scientifically acceptable?

• Never acceptable under any circumstances
• When the disease or target is sex-specific and investigators justify exclusion of the other sex
• Only if the investigator prefers one sex for convenience
• When regulators require reduced animal numbers regardless of science

Correct Answer: When the disease or target is sex-specific and investigators justify exclusion of the other sex

Q15. Which metabolic trait in a species often necessitates selection of that species for hepatic metabolism studies?

• High activity of a human-relevant cytochrome P450 isoform
• Short hair coat
• Small litter size
• Low basal core temperature

Correct Answer: High activity of a human-relevant cytochrome P450 isoform

Q16. Which ethical consideration can influence species selection in preclinical testing?

• Availability of cosmetic markets for test animals
• Higher sentience and social complexity leading to stricter welfare expectations for certain species (e.g., primates, dogs)
• Preference for species that humans find aesthetically pleasing
• Species popularity among pet owners

Correct Answer: Higher sentience and social complexity leading to stricter welfare expectations for certain species (e.g., primates, dogs)

Q17. How can genetic modification (e.g., transgenic mouse models) influence species selection?

• It replaces the need for any nonclinical testing
• Provides a model expressing human targets or disease phenotypes when wild-type species are not predictive
• Genetically modified animals are always preferred by regulators
• It always increases inter-animal variability and is avoided

Correct Answer: Provides a model expressing human targets or disease phenotypes when wild-type species are not predictive

Q18. Which practical consideration often favors the use of rodents over larger species for early screening?

• Rodents have identical organ sizes to humans
• Lower compound requirement and easier housing facilitate dose-range finding and high-throughput screens
• Rodents do not require ethical approval
• Rodents are less sensitive to drugs so effects are easier to detect

Correct Answer: Lower compound requirement and easier housing facilitate dose-range finding and high-throughput screens

Q19. When assessing immunogenicity of a human biologic, selection of animal species should prioritize:

• Species with the closest immune recognition of the biologic target, often non-human primates or species with cross-reactive epitopes
• Smallest available species to reduce cost
• Species that show no immune response to any protein
• Only rodents, because they are standard

Correct Answer: Species with the closest immune recognition of the biologic target, often non-human primates or species with cross-reactive epitopes

Q20. In study design, why is consideration of life-stage (juvenile, adult, aged) important alongside species and sex?

• Life-stage changes physiology, metabolism, and susceptibility to toxicity, affecting relevance to the intended human population
• Only adults are allowed in toxicology studies
• Life-stage affects only behavioral endpoints and is irrelevant to pharmacology
• Younger animals always produce more conservative safety data

Correct Answer: Life-stage changes physiology, metabolism, and susceptibility to toxicity, affecting relevance to the intended human population

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