Preparation and dietary effects of ethoxyquin hydrochloride

Abstract

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.

Ovine urinary metabolites of ethoxyquin

“…), and EQ • HCI was prepared by the method described (Kim, 1985). High-performance liquid chromatography (HPLC) grade acetonitrile (MeCN) was purchased from Fisher (Springfield, N.J.).…”

“…Rats were given EQ/corn oil (0.08 g EQ/d/rat) orally for 7 consecutive days and the urine samples were collected at ambient temperature for a 24-h period following 6 d of dosing. Ethoxyquin (free base) was liberated from crystalline EQ • HCI as described (Kim, 1985) and diluted with corn oil, 0.2 g EQ/ml. The urine samples were stored frozen until analyzed.…”

Accumulation of ethoxyquin in the tissue

“…EQ HCI was prepared as described (Kim, 1985) by converting the available dark oily EQ (a gift from Monsanto) into crystalline EQ HCI and was recrystallized several times from methanol-acetonitrile to give a colorless analytical sample (mp 192-193°C). The standard solution was prepared weekly in methanol (10 mg/ml) and immediately diluted with acetonitrile to 0.1 ^g/m\ and kept in the dark at room temperature.…”

Preparation of ethoxyquin salts and their genotoxic and antioxidant effects on human lymphocytes

“…The comparison of EQ and EQ-HCl effects showed that the animals in EQ-HCl group initially lost weight less than the EQ-group, but then gained it faster. 6 It was also shown that EQ-HCl provided protection against toxic doses of pyrrolizidine alkaloids, and its activity was comparable to that of commercial EQ. 4 In our laboratories we have undertaken studies on cytotoxic, genotoxic and antioxidant activities of EQ (purity > 97%) and new potential antioxidants (including different EQ salts) 7,[9][10][11] after reports on harmful health effects observed in animals fed with EQ-containing feeds.…”