Abstract
Triglyceride-containing lipid emulsions have been designed as caloric sources that can be administered intravenously to patients that cannot meet their nutritional needs by conventional parenteral therapies. In this study, we evaluate the developmental toxicity of a 20% lipid emulsion that contains a 3:1 ratio of medium chain triglyceride (MCT) to one long chain containing lipid emulsion (LCT). This emulsion was administered by intravenous infusion to rats and rabbits at dosages of 1 and 4.28 g lipid/kg body weight (g lipid/kg) at dose volumes of 5 and 21.4 mL/kg, respectively, once daily during organogenesis to assess the potential developmental toxicity of the test article. The control group received 0.9% saline at a dose volume of 21.4 mL/kg. Animals were observed for clinical signs of toxicity and adverse effects on body weights and feed consumption. On Day 20 (rats) or Day 29 (rabbits), females were necropsied and examined for maternal and embryo/fetal toxicity. Fetuses were removed, weighed, and examined for external, soft tissue, and skeletal abnormalities. Dosages of 4.28 g lipid/kg resulted in lower feed consumption for rats and rabbits, an expected finding based on the high-caloric nature of the test article. Potentially test article-related gross necropsy findings, including enlarged lymph nodes and spleen, small thymus, and enlarged renal pelvis, for rats given 4.28 g lipid/kg were present at a low incidence. There were no adverse effects on fetal parameters for rats even in the presence of some maternal toxicity. However, embryo and fetal toxicity (i.e., resorptions) and skeletal abnormalities were present for rabbits given 4.28 g lipid/kg. Under the conditions of this study, the no-observable-effect level for developmental toxicity was greater than or equal to 4.28 g lipid/kg for rats and greater than or equal to 1 g lipid/kg but less than 4.28 g lipid/kg for rabbits.
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