The international validation of a fixed-dose procedure as an alternative to the classical LD50 test.

In an international study involving 33 laboratories in 11 countries, the acute oral toxicity to the rat of 20 substances and preparations was evaluated using a fixed-dose procedure and the results compared with those obtained for the test materials using the classical LD50 test. The study has shown that the fixed-dose approach to acute oral toxicity testing: (1) produces consistent results that are not substantially affected by inter-laboratory variations; (2) provides adequate information for risk assessment purposes on signs of toxicity, including their nature, time to onset, duration and outcome; (3) uses fewer animals than the current internationally agreed OECD procedure (Guideline 401-revised); (4) subjects animals to less pain and distress than the classical LD50 test and causes less compound-related mortality; and (5) enables substances and preparations to be ranked according to the EEC classification system on the basis of their acute oral toxicity, such ranking being compatible with that allocated by the results of classical LD50 studies.