The disposition and toxicology of retinyl methyl ether in rats dosed orally

In disposition studies, retinyl methyl ether (RME) was administered to rats in oral doses of 10 or 40 mg/kg. For the high dose, RME was eliminated from plasma with a terminal half-life of 19.5 hr but for the low dose the terminal phase could not be determined. For both doses, the concentrations of RME in the tissues examined (liver, spleen, adrenals, and mammary glands) were greater than those in plasma. In the adrenals of rats given the low dose, concentrations were as much as 10- to 100-fold higher. Concentrations of RME in the mammary gland, a site for chemopreventive activity, were also relatively high (about 1000 ng/g for the low dose and about 4000 ng/g for the high dose), and there was an elimination phase with a half-life of 63-81 hr. After administration of RME, the concentration of retinyl esters in the liver did not increase, and no retinyl esters were detected in the mammary gland. For toxicology studies, rats were administered 20, 40, and 80 mg/kg of RME or retinyl acetate (ROAc) daily for 28 days. The toxic effects of RME were similar to those of ROAc. At equivalent mg/kg doses, weight gain depressions, bone fractures, elevations in serum triglycerides, anemia, elevations in cholesterol in females, and reductions in serum albumin were similar.(ABSTRACT TRUNCATED AT 250 WORDS)