Acute Toxicity Studies - Study Design of OECD 423 Acute Oral

The OECD 423 Acute Oral Toxicity Test Guideline is a stepwise procedure used to determine the acute oral toxicity of a substance in rodents, typically rats. It is designed to minimize the number of animals used while providing enough information to classify the substance according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Objectives:

  • Determine the LD50 (lethal dose at which 50% of the exposed animals die) or estimate it within a defined range.
  • Observe and record general signs of toxicity, mortality, and any gross necropsy findings.
  • Classify the substance according to the GHS acute oral toxicity categories.

Test Method:

  • Animals: A single sex (usually females) of healthy young adult rats are used. The number of animals depends on the chosen dose levels and test phases.
  • Dosing: The test substance is administered orally by gavage (stomach tube) at defined starting doses based on the expected toxicity class.
  • Observation: Animals are observed for at least 14 days after dosing for mortality, morbidity (signs of illness), and behavioral changes. Detailed clinical observations are made at regular intervals during the first 24 hours, with less frequent observations for the remaining period.
  • Necropsy: All animals that die or are euthanized during the study are subjected to a gross necropsy to identify any organ lesions that might be related to the test substance.

Stepwise Procedure:

  • The test starts with a fixed initial dose based on the GHS classification categories.
  • Animals are observed for 14 days, and the mortality rate is determined.
  • Depending on the mortality rate, the next dose level (higher or lower) is chosen according to a fixed decision tree.
  • This process is repeated until sufficient information is obtained to classify the substance.

Endpoints:

  • Mortality rate at different dose levels.
  • Time to death of animals.
  • Clinical signs of toxicity (e.g., lethargy, tremors, convulsions).
  • Gross necropsy findings.
  • LD50 value or an estimate within a defined range.
  • GHS classification for acute oral toxicity.

Benefits of OECD 423:

  • Standardized and internationally accepted method.
  • Minimizes animal use compared to traditional fixed-dose methods.
  • Provides sufficient information for GHS classification.

Limitations of OECD 423:

  • Does not provide information on chronic or subchronic effects.
  • Does not identify specific target organs of toxicity.
  • May not be suitable for highly corrosive or volatile substances.

Here are some additional resources that you may find helpful:

 

 

 

img1
Please visit our blog at linkedin

Solverwp- WordPress Theme and Plugin

Scroll to Top