Acute toxicity studies: oral, dermal, inhalational per OECD MCQs With Answer

Introduction
Acute toxicity studies assess the adverse effects that occur following a single or short-term exposure to a substance. For M.Pharm students, understanding OECD acute toxicity procedures (oral, dermal, inhalational) is essential for designing studies, interpreting LD50/LC50 data, and meeting regulatory and ethical requirements. This blog provides focused multiple-choice questions based on OECD Test Guidelines (e.g., 420, 423, 425, 402, 403) with answers to reinforce key concepts: study objectives, dosing strategies, limit tests, observation periods, animal selection, exposure methods, endpoint interpretation, and humane endpoints. These questions emphasize practical and regulatory considerations relevant to toxicological screening and safety classification.

Q1. Which OECD guideline is primarily used for the Fixed Dose Procedure in acute oral toxicity testing?

• OECD 401
• OECD 420
• OECD 425
• OECD 423

Correct Answer: OECD 420

Q2. Which acute oral toxicity guideline uses groups of three animals per step, often using female animals, to determine the toxic class?

• OECD 425 (Up-and-Down)
• OECD 420 (Fixed Dose)
• OECD 423 (Acute Toxic Class)
• OECD 402 (Dermal Acute)

Correct Answer: OECD 423 (Acute Toxic Class)

Q3. In the Up-and-Down Procedure (OECD 425), which principle best describes the dosing approach?

• Simultaneous dosing of cohorts of five animals at several fixed doses
• Sequential dosing of single animals with dose adjusted up or down based on prior response
• Administration of only a limit dose to all animals
• Use of groups of three animals with predetermined fixed steps

Correct Answer: Sequential dosing of single animals with dose adjusted up or down based on prior response

Q4. What is the commonly accepted observation period after acute administration in OECD acute toxicity studies?

• 48 hours
• 7 days
• 14 days
• 28 days

Correct Answer: 14 days

Q5. Which endpoint is primarily estimated in acute toxicity testing and used for regulatory classification?

• NOAEL (No Observed Adverse Effect Level)
• LD50 or LC50 (median lethal dose or concentration)
• Chronic toxicity index
• Reproductive toxicity score

Correct Answer: LD50 or LC50 (median lethal dose or concentration)

Q6. For acute dermal toxicity per OECD 402, what is the typical exposure duration of the test substance on the skin?

• 1 hour continuous exposure
• 4 hours continuous exposure
• 24 hours (occluded or semi-occluded)
• 7 days continuous application

Correct Answer: 24 hours (occluded or semi-occluded)

Q7. In inhalation acute toxicity testing (OECD 403), which exposure duration is most commonly used to determine LC50 for vapors, gases, or aerosols?

• 30 minutes
• 1 hour
• 4 hours
• 24 hours continuous exposure

Correct Answer: 4 hours

Q8. Which of the following is the recommended test species and sex preference for many OECD acute oral toxicity tests when no sex differences are known?

• Mice, males
• Rats, females
• Rabbits, males
• Guinea pigs, mixed sexes

Correct Answer: Rats, females

Q9. In dermal acute testing, what approximate percentage of total body surface area is typically used for application site preparation in rodents?

• 1% of body surface area
• 10% of body surface area
• 50% of body surface area
• 100% of body surface area

Correct Answer: 10% of body surface area

Q10. Which measurement unit is typically used to express acute inhalation LC50 for dusts, mists, and vapors?

• mg/kg bw
• mg/L (air) or mg/m3
• mg/cm2
• mL/kg

Correct Answer: mg/L (air) or mg/m3

Q11. Which of the following is a key refinement/humane endpoint recommended to minimize animal suffering in acute toxicity tests?

• Extending observation to 28 days regardless of signs
• Allowing animals to die to determine exact time of death
• Termination of an animal based on predefined severe clinical signs before death
• Using higher doses to reduce the number of animals needed

Correct Answer: Termination of an animal based on predefined severe clinical signs before death

Q12. Which OECD guideline applies specifically to acute dermal toxicity testing?

• OECD 425
• OECD 402
• OECD 403
• OECD 420

Correct Answer: OECD 402

Q13. What is the primary regulatory purpose of performing a limit test in acute toxicity studies?

• To determine chronic toxicity endpoints
• To evaluate multiple dose–response curves
• To demonstrate lack of significant toxicity at a predetermined high dose (e.g., 2000 mg/kg)
• To replace LD50 determination with histopathology-only endpoints

Correct Answer: To demonstrate lack of significant toxicity at a predetermined high dose (e.g., 2000 mg/kg)

Q14. Under GHS classification for acute oral toxicity, what LD50 range corresponds to Category 4?

• ≤5 mg/kg
• >50 to ≤300 mg/kg
• >300 to ≤2000 mg/kg
• >2000 to ≤5000 mg/kg

Correct Answer: >300 to ≤2000 mg/kg

Q15. Which exposure method is preferred in inhalation studies to limit dermal or oral contamination and better control delivered dose?

• Dietary exposure
• Drinking water exposure
• Whole-body exposure
• Nose-only exposure

Correct Answer: Nose-only exposure

Q16. Which of the following is TRUE regarding the Fixed Dose Procedure (OECD 420) compared with classical LD50 tests?

• It uses larger numbers of animals to increase precision of LD50
• It aims primarily to estimate an exact LD50 value using probit analysis
• It reduces animal use and focuses on identifying a dose producing clear signs of toxicity without necessarily calculating LD50
• It requires chronic exposure over 90 days

Correct Answer: It reduces animal use and focuses on identifying a dose producing clear signs of toxicity without necessarily calculating LD50

Q17. When conducting an acute inhalation test, which aerosol characteristic must be monitored to ensure reliable interpretation of results?

• Particle size distribution (MMAD and GSD)
• Water solubility only
• Oral bioavailability
• Topical pH on skin

Correct Answer: Particle size distribution (MMAD and GSD)

Q18. Which statement best describes the primary difference between OECD 423 and OECD 425 acute oral procedures?

• OECD 423 uses sequential single-animal dosing; OECD 425 uses fixed groups of five
• OECD 423 is a fixed-dose group procedure using small cohorts; OECD 425 is an up-and-down sequential single-animal procedure
• Both are identical in design and interchangeable without justification
• OECD 423 is for inhalation and OECD 425 is for dermal testing

Correct Answer: OECD 423 is a fixed-dose group procedure using small cohorts; OECD 425 is an up-and-down sequential single-animal procedure

Q19. For dermal acute toxicity, what is a common rationale for using an occlusive dressing during application?

• To increase grooming by the animal for better absorption
• To prevent ingestion and to maximize dermal contact for consistent exposure
• To allow evaporation and reduce dose consistency
• To increase airborne concentration for inhalation assessment

Correct Answer: To prevent ingestion and to maximize dermal contact for consistent exposure

Q20. Which of the following best reflects the 3Rs (Replacement, Reduction, Refinement) principle application in modern acute toxicity testing?

• Only replacement: completely removing animals without alternative assessment
• Using the largest possible doses to minimize number of animals
• Designing studies (e.g., OECD 420/423/425) to use fewer animals, limit suffering, and apply non-animal methods where possible
• Refusing regulatory testing entirely

Correct Answer: Designing studies (e.g., OECD 420/423/425) to use fewer animals, limit suffering, and apply non-animal methods where possible

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