Preparation and dietary effects of ethoxyquin hydrochloride

Ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) was purified and converted to a crystalline, stable ethoxyquin hydrochloride (EQ-HCl). The readily available (technical grade) oily EQ reacted with concentrated hydrochloric acid (HCl) and precipitated as a crystalline salt (EQ-HCl) in acetone, leaving most of the impurities in solution. The regenerated free base (EQ) from the EQ-HCl was further purified by silicagel column chromatography to remove several minor contaminants, and the pure unstable EQ was immediately converted into a pure stable salt (EQ-HCl). The dietary administration of EQ-HCl, 0.25 or 0.5% in the feed, induced hepatic and intestinal thiols in mice and provided protection against toxic doses of pyrrolizidine alkaloids. The LD50 values of the 0.125 and 0.25% EQ-HCl-pretreated mice were 94.0 and 98.5 mg/kg, respectively, compared to that of controls, 71.3 mg/kg. The EQ-HCl-supplemented feed appeared to be more palatable, but other effects, such as the hepatic hypertrophy, the tissue thiol induction, and the protective effects, were comparable to those of unpurified EQ.