Validation of a modified 28-day rat study to evidence effects of test compounds of the immune system

The toxicology profile of new test compounds is ascertained in repeat-dose toxicity studies with exposure over 4 weeks or 3 months which yield a range between a high dose causing overt toxicity and a low dose with no observable (toxic) effect. In recent years, the immune system has been identified as a target of the direct toxic action of chemicals (Dean et al., 1989). A first step to the EU level to developed a test program to detected undesired effects on the immune system was undertaken in Luxembourg in 1984 (Berlin et al., 1987) . In consequence of this international activity, a number of collaborative studies were initiated. The aim of these studies was to select and validate available testing procedures in a tiered approach to find out their appropriateness of indicating adverse effects on the immune system after exposure to chemicals (Vos and vanLoveren, 1987; Hess et al., 1990). In a collaborative toxicity study initiated and coordinated by the Federal Institute for Health Prot ection of Consumers and Veterinary Medicine, four industrial laboratorys and one independent institute participated. The purpose of this study was to qualify and validate additional investigation (i.e., enhanced pathology, functional tests) within an ordinary subacute toxicity test protocol (Annex V, 67/548/EEC; OECD 407) to identify the effects of chemicals on the immune system during their regular safety evaluation.