An analysis of the chronic oral toxicity of polyether ionophore antibiotics in animals.

Feeding well-mixed ionophores to adapted cattle improves ruminal fermentation and growth rates. In nonruminants, growth is improved by reducing competing gastrointestinal microorganisms. Interactions of monensin with other drugs may be beneficial or toxic. Tiamulin and furazolidone potentiate monensin's negative effects. For example, monensin produces positive inotropy and cardiomyopathy dependent on calcium and extracellular sodium. Based on available toxicity data and derived no observable effect levels (NOEL) in the same species and across species, monensin was more toxic than salinomycin, lasalocid or narasin. Lasalocid was 5- to 10-fold less toxic to horses than is monensin. Based on available toxicity data and derived NOEL, lasalocid was less toxic than all ionophores except salinomycin. Very high levels of narasin caused death in sows, leg muscle weakness in turkeys, and cardiopulmonary clinical signs in 15% of the rabbits from Brazilian rabbit farms. Only salinomycin and lasalocid were less toxic than narasin. Salinomycin was the least toxic of all the ionophores. Maduramicin was the most toxic of all the ionophores. Nearly all maduramicin fed to poultry persists in litter (manure), making this poultry litter toxic if fed to cattle as a nitrogen source. While ionophore comparative toxicity was difficult to estimate, most cross-comparisons utilized NOEL within and across species. The relative toxicities of the ionophores from lowest to highest were salinomycin < lasalocid < or = narasin < or = monensin (but lasalocid < monensin) < maduramicin.