The approximate LD₅₀ and cumulative effect of 4 bufadienolides, isolated from Cotyledon orbiculata, were determined in guinea-pigs. Two of the bufadienolides proved to be mildly cumulative. One of the mildly cumulative bufadienolides induced subacute intoxication with some signs of krimpsiekte when injected intravenously into a sheep over 13 days. In the sheep, the paralysis was accompanied by signs of malaise, such as electrocardiographic changes and ruminal stasis.
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