HIGH-LEVELS OF DIETARY ARACHIDONIC-ACID TRIGLYCERIDE EXHIBIT NO SUBCHRONIC TOXICITY IN RATS

Arachidonic acid (AA), an n-6 long-chain polyunsaturated fatty acid (L C-PUFA), serves an important role in the body as a structural fatty ac id of many tissues including neurological tissues. It is also a precur sor of the n-6 class of eicosanoids and is the most abundant n-6 LC-PU FA found in human breast milk. We have optimized the production of a m icrofungal source of a triglyceride oil (ARASCO(R)) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO(R) in Sprague-Dawley rats (20 /sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of th e oil. Two groups of control animals received either untreated standar d laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body we ight, food consumption, clinical chemistry, hematology parameters, neu robehavioral assessments, and macroscopic as well as microscopic postm ortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose AR ASCO(R)-fed animals increased by 8, 59, and 76%, respectively, indicat ing that the AA in the oil was readily incorporated into tissue lipids . In spite of this high elevation in tissue AA levels, no developmenta l, histopathological, or neuropathological differences were seen in th e animals administered ARASCO(R) compared with the vehicle control ani mals. Being highly enriched in AA, ARASCO(R) offers the means to study the effect of this fatty acid in experimental settings and in human m etabolic studies.