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Tri-O-Cresyl Phosphate as a Vitamin E Antagonist for the Rat and Lamb¹

Four Figures

Division of Animal Nutrition, University of Illinois, Urbana

Newborn lambs were fed a purified "synthetic milk" diet deficient in vitamin E and containing tocopherol-low molecular-distilled lard as a source of fat. Those animals maintained on this basal diet for about 7 weeks exhibited either paralysis of the legs or anorexia and weight loss. Addition of tri-o-cresyl phosphate to the basal diet (0.4 to 1.0 gm per liter of "milk" containing 19.5% dry matter) caused either severe leg weakness or sudden death after approximately 4 weeks. The effects of this compound could be delayed or prevented, but not cured, by oral administration of synthetic DL-alpha-tocopherol acetate at a rate of 100 mg per week. Lambs showing paresis induced by tri-o-cresyl phosphate ingestion died within three days despite the administration of large amounts of tocopherol either orally or intravenously as an emulsion. The outward manifestations of vitamin E deficiency obtained by feeding this diet, in addition to the muscular dystrophy, creatinuria and low plasma tocopherol levels also observed, indicate that the syndrome is identical with "stiff-lamb disease" which occurs among the suckling offspring of ewes fed a vitamin E-low practical ration. Abnormalities in the electrocardiograms of paralytic lambs were also detected. In a corollary experiment, it was found that when the basal diet was fed to rats, the addition of tri-o-cresyl phosphate (2 mg per gram) induced earlier development of a vitamin E deficiency, as identified by growth depression and the hemolysis test of Rose and György ('50), than was obtained on the basal regimen alone. Supplementation with synthetic DL-alpha-tocopherol acetate (24 mg per 100 gm diet) prevented the occurrence of deficiency symptoms in rats receiving the above level of tri-o-cresyl phosphate in the diet over a 10-week period.

Manuscript received 7 April 1952.