Evaluation of single-cell sources of docosahexaenoic acid and arachidonic acid: 3-month rat oral safety study with an in utero phase

Owing to the presence of the polyunsaturated fatty acids (PUFA) docosahexae noic acid (DHA) and arachidonic acid (ARA) in human milk and their importan t biological function, several authorities recommend that they be added to infant formulas. This study assessed the safety of an algal oil rich in DHA and a fungal oil rich in ARA, blended to provide a DHA to ARA ratio simila r to human milk. The oil blend was incorporated into diets and fed to rats such that they received 3, 11 and 22 times the anticipated infant exposure to DHA and ARA. Low-fat and high-fat control groups received canola oil. Ra ts received experimental diets over a premating interval and throughout mat ing, gestation and lactation. Pups born during this period (F-1) consumed t reatment diets from weaning for 3 months. Physical observations, ophthalmos copic examinations, body weight, food intake, clinical chemistry, neurobeha vioural evaluations and postmortem histopathology of selected tissues were performed. No statistically significant, dose-dependent adverse effects wer e seen in reproductive performance or fertility, nor in the neonates from b irth to weaning. Mid- and high-dose treated F-1 animals exhibited increased white cell count, neutrophil count and blood urea nitrogen; increased live r and spleen weights (absolute and relative to body weight) also were obser ved. There were no corresponding microscopic findings. The clinical patholo gy and organ weight differences at these treatment levels represent physiol ogical or metabolic responses to the test substance rather than adverse res ponses. These single-cell oils produced no adverse effects in rats when adm inistered in utero and for 90 days at dietary levels resulting in exposures up to 22 or 66 times higher than those expected in infant formulas when ex trapolated on the basis of diet composition (g/100 Cat) or intake (g/kg bod y weight), respectively. (C) 1998 Elsevier Science Ltd. All rights reserved .