At their November meeting in 2001, the OECD Joint Meeting of the Chemicals Committee and Working Party on Chemicals, Pesticides and Biotechnolgy, agreed that the LD50 for acute oral toxicity, known as OECD Test Guideline 401 and heavily criticised by the animal welfare protectorate shall be abolished and deleted from the OECD manual of internationally accepted Test Guidelines. Delegates agreed that the three alternative methods now available for this disputed animal test can provide sufficient information to replace Guideline 401. Subsequent to this agreement OECD Council adopted the Decision to delete Guideline 401 by 17 December 2002.
The disputed test
The principle of the LD50 test, developed almost 50 years ago, is to dose groups of animals with a single dose of a test substance at concentrations expected to cause death in at least a fraction of the animals dosed. Normally at least 20 animals are used for the test. Results of the test enable the calculation of the so-called LD50 value, being the dose that would kill 50% of the animals within 14 days after a single exposure. This type of information provides an important basis for the safety assessment of chemical substances for humans and mammalian wildlife, and is crucial when considering accidental exposures at the workplace, of young children at home and (for environmental assessments) following transport accidents.
Considering that the severe suffering of a substantial number of animals in the LD50 test is no longer acceptable while at the same time recognising the importance of the information provided by the test, experts from the UK, Germany and the USA took the lead in the development of three alternative tests.
The three alternative methods were adopted during the 1990's as OECD Test Guidelines 420, 423, and 425, respectively. However, in 1998 it appeared that all three methods needed extensive revision to consider further reduction in the numbers of animals while improving their performance characteristics. Revision of the alternative methods was completed in June 2001and the updated methods were adopted by Council in December 2001. Although the revised alternative methods still require the use of animals, the numbers of animals needed for any of the alternatives are drastically reduced and would normally be well below one-third of those used for the conventional LD50 test. Moreover, one of the alternative tests (Guideline 420) does not require the death of animals as an endpoint, whereas for the other alternatives (Guidelines 423 and 425) the expected number of deaths is typically not more than 3.
The OECD Member countries' Delegates agreed that a "phasing-out" period of one year should be considered before studies conducted according to the deleted Guideline 401 would be rejected by the regulatory community. This would allow industry, test laboratories and regulatory community ample time to introduce and familiarise with the new methods. To this end the date of formal deletion was set at 17 December 2002, which is exactly one year after the adoption of the alternative methods.
Document C(2001)282 comprises the Council Decision on the deletion of Guideline 401. Questions and inquiries should be addressed to laurence Musset, Principal Administrator of the Test Guidelines Programme [e-mail: email@example.com].