Immunotoxicological assessment of cyclosporin A by conventional pathological techniques and immune function testing in the rat.
1. Groups of male rats were given different doses of cyclosporin A, ranging from the maximum tolerated dose (20 mg/kg/day) downwards, 7 days a week for 28 days using a protocol derived from OECD test guideline 407. 2. At the end of the test, one set of animals underwent a detailed necropsy and histopathological examination of lymphoid tissues. Immune function was assessed using the lymphoproliferative response and natural killer cell activity of their spleen cells. Another set of animals was immunised with sheep erythrocytes on day 25 and used to evaluate the ability to produce specific anti-sheep red blood cell antibody. 3. Cyclosporin A produced detectable effects on the immune system at all doses and at doses lower than other toxic effects. Both histopathological techniques and one of the immune function tests were able to identify changes at the lowest dose, 1.25 mg/kg/day. 4. The results of this investigation suggest that conventional histopathological techniques, if applied to a range of lymphoid organs, are sufficient to identify potential immunotoxicants without recourse to immune function tests.
Crevel
R W
RW
Environmental Safety Laboratory, Unilever Research and Engineering, Sharnbrook, Bedford, UK.
Buckley
P
P
Robinson
J A
JA
Sanders
I J
IJ
D000818:Animals; D001259:Ataxia / Q000097:blood / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D007159:Immunologic Tests; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D007166:Immunosuppressive Agents; D016572:Cyclosporine