Exploring waiving opportunities for mammalian acute systemic toxicity tests

Area of Science:

• Toxicology
• Regulatory Science
• Chemical Safety Assessment

Background:

• Mammalian acute systemic toxicity tests are crucial for chemical safety assessment.
• The EU REACH Regulation mandates stringent chemical registration deadlines, driving the need for efficient testing strategies.
• Waiving certain toxicity tests is desirable to reduce animal use and testing costs.

Purpose of the Study:

• To explore opportunities for waiving mammalian acute systemic toxicity tests.
• To determine if sub-acute toxicity test data can predict acute systemic toxicity test outcomes.
• To assess expert opinions on toxicity testing waiving strategies.

Main Methods:

• A survey was conducted among toxicity testing experts.
• A retrospective data analysis of registered chemicals with available acute and sub-acute oral toxicity data was performed.
• Data analysis focused on oral administration routes.

Main Results:

• Experts expressed willingness to adopt toxicity testing waiving opportunities.
• Sub-acute toxicity or dose-range finding study data may predict chemicals not requiring acute oral toxicity classification (LD50 > 2000mg/kg).
• Predicting other acute oral toxicity categories using available data is difficult.

Conclusions:

• Sub-acute toxicity data shows potential for predicting non-classified acute oral toxicity, facilitating test waiving.
• Further research is needed to improve prediction accuracy for other acute toxicity categories.
• The findings support the development of alternative approaches in chemical safety testing.