The Toxicity of Tri-O-Cresyl Phosphate for Rats as Related to Dietary Casein Level, Vitamin D and Vitamin A

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Abstract
Growth inhibition of rats fed diets containing 0.1% of tri-o-cresyl phosphate was only partially prevented by vitamin E even at high levels. However, high dietary casein levels allowed almost normal growth even in the absence of vitamin E. Liver, brain and carcass lipids from rats fed tri-o-cresyl phosphate showed increased conjugated dienes, decreased apparent arachidonic acid and decreased tocopherol levels. Supplements of vitamin E resulted in nearly normal values for these factors. Increased dietary casein levels, even without vitamin E, largely prevented the lipid changes. In control rats, increased casein levels resulted in an increased arachidonic acid content of tissues. Tri-o-cresyl phosphate decreased liver vitamin A deposition in rats fed β-carotene or, to a lesser degree, vitamin A acetate. In vitro studies revealed a pro-oxidant effect of trio-o-cresyl phosphate, carbon tetrachloride, pyridine and pentachloronaphthalene in catalyzing the destruction of carotene in the presence of fat-peroxide. Limited data have shown that X-disease in cattle (chloronaphthalene poisoning) is associated with a decrease of plasma tocopherol as well as plasma vitamin A. An hypothesis is advanced relating the toxic mechanism of the fat-soluble toxic chemicals to their generalized oxidative action in unsaturated lipid systems.