EXTENSION OF THE PROTOCOL OF OECD-GUIDELINE-407 (28-DAY REPEATED DOSEORAL TOXICITY TEST IN THE RAT) TO DETECT POTENTIAL IMMUNOTOXICITY OF CHEMICALS

To indicate the immunotoxic potential of chemicals the examinations pr escribed by OECD Guideline 407 were extended by the following addition al toxicological, haematological, histopathological, and immune functi on examinations: absolute and relative organ weight of spleen, thymus, popliteal lymph nodes, lung and brain; histopathology of thymus, mese nteric lymph nodes, popliteal lymph nodes, bone marrow (femur), Peyer' s patches (ileum),lungs and colon; PFC assay (spleen), T cell prolifer ation and NK cell assay. Two well known immunosuppressants Azathioprin e (AZA) and Cyclosporine (CysA) were chosen as model compounds at a do se range which do not cause visible toxic signs on the animals during a 28 days treatment period. The results show that the applied experime ntal system is much more sensitive in detection of the immunotoxic pot ential of these two compounds in a low dose range than the examination required by OECD Guideline 407 are.