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.
Administration of anaesthetic agents modifies the methaemoglobin formation induced by aniline in cats. The maximum amount of methaemoglobin is reduced, so too is the rate at which the methaemoglobin disappears. Studies with phenylhydroxylamine indicate that these changes are due to anaesthetics modifying the metabolism of aniline to phenylhydroxylamine rather than modifying the action of phenylhydroxylamine on systems within the red blood cell. The microsomal metabolism inhibitor SKF 525A has no effect on methaemoglobin formation induced by aniline.
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