Acute Toxic Class Methods: Alternatives to LD/LC50 Tests.

Area of Science:

• Toxicology
• Chemical Safety Assessment
• Regulatory Science

Background:

• Traditional LD/LC50 tests for acute toxicity assessment are resource-intensive and ethically concerning due to high animal usage.
• The Acute Toxic Class (ATC) methods were developed as alternative approaches to reduce animal numbers in toxicity testing.
• Existing ATC methods have demonstrated comparable or superior reliability in classifying chemical toxicity compared to traditional LD/LC50 tests.

Purpose of the Study:

• To present the development and validation of Acute Toxic Class (ATC) methods for oral, dermal, and inhalation routes as alternatives to LD/LC50 tests.
• To highlight the reduced animal usage and maintained or improved reliability of ATC methods.
• To address the need for revising ATC methods to align with the Global Harmonisation System (GHS) for classification of acute toxicity.

Main Methods:

• Stepwise testing procedures using a limited number of animals (max 6) per dose/concentration.
• Biometric basis utilizing the Probit model for data analysis and classification probability determination.
• Validation through animal ring studies and biometric evaluations for the oral ATC method; biometric development for dermal and inhalation routes.

Main Results:

• ATC methods use 40-90% fewer animals compared to LD/LC50 tests.
• Reliability for toxicity classification is comparable or better than LD/LC50 tests.
• The oral ATC method is an official OECD and EU Test Guideline, validated through ring studies with excellent agreement between animal data and biometric evaluations.

Conclusions:

• ATC methods provide a scientifically sound and ethically favorable alternative to traditional acute toxicity tests.
• The oral ATC method is established and widely used, with strong validation support.
• Revision of all three ATC methods is necessary to incorporate the Global Harmonisation System (GHS) for enhanced regulatory alignment.