Thirteen cationic ionophores: their acute toxicity, neurobehavioral and membrane effects

Thirteen cationic ionophores (12-Crown-4, 15-Crown-5, 18-Crown-6, Dibenzo 18-Crown-6, Dicyclohexano 18-Crown-6, 24-Crown-8, Dicyclohexano 24-Crown-8, Lasalocid, Hexacyclen trisulfate, Chiral binapthol, Valinomycin, Monensin, and A-23187) were evaluated for acute toxicologic properties, including lethality and neurobehavioral effects in multiple species (rats, rabbits, and mice) by multiple routes, skin and eye irritation and effects on membrane permeability to physiologic cations. Attention was focused on determining minimum neurobehavioral effect levels and characterizing the spectrum of these effects at different dose levels. While LD50's followed one pattern, this was not the case with other effects. Cluster and factor analysis suggest that, though the primary mechanism of action is alteration of membrane permeability to specifi-cations (qualitative types of activity correlate with the results of membrane permeability studies), which ions are provided an increased passage varies with ring size and charge dispersion. In the intact animal absorption markedly modifies these results.