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Human & Experimental Toxicology
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Immunotoxicological assessment of cyclosporin A by conventional pathological techniques and immune function testing in the rat

RWR Crevel

Environmental Safety Laboratory, Unilever Research and Engineering, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK

P. Buckley

Environmental Safety Laboratory, Unilever Research and Engineering, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK

JA Robinson

Environmental Safety Laboratory, Unilever Research and Engineering, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK

IJ Sanders

Environmental Safety Laboratory, Unilever Research and Engineering, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK

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 guide line 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 conven tional histopathological techniques, if applied to a range of lymphoid organs, are sufficient to identify potential immunotoxicants without recourse to im mune function tests.

Key Words: Immunotoxicology • repeat dose 28-day study • histo pathology • immune function tests

Human & Experimental Toxicology, Vol. 16, No. 2, 79-88 (1997)
DOI: 10.1177/096032719701600203


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