WRITTEN QUESTION E-4136/97 by David Bowe (PSE) to the Commission (21 January 1998)

Subject: The LD50 test for toxic chemicals

Given that the current test for the safety of toxic chemicals coming into prolonged human contact is the LD50 test (the amount of a chemical which will kill half the population of the species under experimentation, usually rats, and expressed in milligrams per kilogram of body weight), what action does the Commission propose to take to ensure that adequate research is undertaken as to the chronic effects on humans of exposure to lower levels over a longer term?

Answer given by Mrs Bjerregaard on behalf of the Commission (12 March 1998)

Within Community chemical legislation, Annex V to Council Directive 67/548/EEC of 27 June 1967 on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances ((OJ 196, 16.8.1967. )) contains a number of methods for the determination of the toxicity of

dangerous substances. These methods are based on those recognised and recommended by competent international bodies (in particular the Organisation for economic co-operation and development (OECD)). Among these methods, there are tests for short-term toxicity (acute toxicity), medium-term toxicity (sub-chronic toxicity) and long-term toxicity (chronic toxicity). Only short-term toxicity tests provide LD50 values. Thus LD50 is used to evaluate short-term toxicity, but not medium-term toxicity nor long-term toxicity.

OECD test guideline 401 is a method for the determination of oral acute toxicity and provides LD50 values. A corresponding method is included in Annex V to Directive 67/548/EEC. The Commission has recently requested deletion of OECD test guideline 401 because reliable alternatives exist. For instance Annex V to Directive 67/548/EEC contains two test methods for acute toxicity (oral) that use fewer animals and minimise animal suffering. Similarly, the Commission would proceed to delete the corresponding test method from Annex V.

Chronic toxicity tests included in Annex V to Directive 67/548/EEC check the adverse effects occurring in experimental animals as a result of the regular administration of a substance for a major part of their life span. These long-term tests use lower doses during more extended periods and take into account not only mortality but also clinical observations, examination of animal tissues and laboratory analyses.

Under the fourth framework programme for research and technological development (RTD) activities (1994-1998) ((OJ L 126, 18.5.1994. )) research on toxicity testing is being funded through the following specific programmes:

i) the Environment and climate research programme is currently undertaking research on chemicals safety testing and assessment for hazards to both humans and the environment;

ii) the Standards, measurements and testing programme, where the research tasks focus on the development of new or alternative (replacement of animal testing) testing methods.

These research topics are included in the Commission's proposal for the fifth framework programme for RTD activities (1998-2002) ((COM(98) 8 final. )).

In the area of pharmaceutical products, the test that provided LD50 values was abandoned a long time ago.

Community legislation is constantly being updated according to scientific and technical progress so as to ensure a high level of protection of man and the environment.