Toxicity Testing of Fat Emulsions for Intravenous Administration

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Abstract
Clinical and histopathologic toxicity studies were conducted on fourteen fat emulsions including Lipomul, Intralipid, Lipofundin and cottonseed or soybean oil emulsions prepared commercially or experimentally for intravenous use. These emulsions were administered to rabbits and/or rats in a daily dose of 2.0 to 3.0 gm. of fat per kg. of body weight. Clinical studies included observation of the animals' general reaction to the infusion, local reaction at the site of injection, variation in body weight, and weekly hemograms and urinalyses. The animals were sacrificed at least ten days after infusion and a detailed necropsy was performed. No gross lesions could be attributed to the fat emulsion. However, histopathologic examination revealed the deposition of intravenous fat pigment in the liver and spleen of every animal. The most pigment was found in animals given cottonseed oil emulsions and the least in animals given emulsion SR-151. Lipoid granulomas were observed in all test animals except those given emulsion SR-141. Mild hepatic fibrosis was observed in animals receiving Lipofundin. Adverse clinical reactions in rabbits included death in two animals, produced by Lipofundin K399, and hyperpyrexia, anorexia, decreased water intake, weight loss, and decrease in hemoglobin and hematocrit following infusion. The best performance in rabbits was obtained with Intralipid 293011 and in rats with SR-4734-107A. Although Lipofundin was well tolerated by rats, in general, soybean oil-egg yolk phosphatide-glycerol type emulsions produced the least adverse physiologic and histopathologic changes in the test animals.