While C. tomentosa may be vulnerable to trampling by livestock, it is also known to be poisonous to livestock, dogs, and humans. Cotyledon species are known to contain cardiac glycosides, including bufadienolides, which are highly toxic to cattle, sheep, goats, and other livestock. The bufadienolides found in Cotyledon cause both acute and chronic poisoning. On the World Health Organization toxicity scale, cardiac glycosides are considered Class Ia, "extremely hazardous," and a dose of only 1.0 g/kg body weight of a related species, Cotyledon orbiculata, was lethal when fed to sheep.
