Extension of the protocol of OECD guideline 407 (28-day repeated dose oral toxicity test in the rat) to detect potential immunotoxicity of chemicals.
To indicate the immunotoxic potential of chemicals the examinations prescribed by OECD Guideline 407 were extended by the following additional toxicological, haematological, histopathological, and immune function examinations: absolute and relative organ weight of spleen, thymus, popliteal lymph nodes, lung and brain; histopathology of thymus, mesenteric lymph nodes, popliteal lymph nodes, bone marrow (femur), Peyer's patches (ileum), lungs and colon; PFC assay (spleen), T cell proliferation and NK cell assay. Two well known immunosuppressants Azathioprine (AZA) and Cyclosporine A (CysA) were chosen as model compounds at a dose range which do not cause visible toxic signs on the animals during a 28 days treatment period. The results show that the applied experimental system is much more sensitive in detection of the immunotoxic potential of these two compounds in a low dose range than the examination required by OECD Guideline 407 are.
Institóris
L
L
Department of Public Health, Albert Szent-Györgyi University Medical School, Szeged, Hungary.
Siroki
O
O
Dési
I
I
Lesznyák
J
J
Serényi
P
P
Szekeres
E
E
Petri
I
I
D000284:Administration, Oral; D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage / Q000633:toxicity; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity; D003602:Cytotoxicity, Immunologic; D017408:Guidelines as Topic; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects; D008221:Lymphoid Tissue / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects*; D018675:Toxicity Tests
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine