Preclinical safety evaluation in rats using a highly purified ethyl ester of algal-docosahexaenoic acid

Preclinical studies have shown that docosahexaenoic acid (DHA) derived from microalgae (DHASCO®) is neither mutagenic nor toxic in acute, subchronic or developmental tests. DHASCO®, triglyceride oil from the fermentation of Crypthecodinium cohnii, contains 40–50% (400–500 mg/g) of DHA by weight. Martek Biosciences Corporation has developed a concentrated ethyl ester of DHA (900 mg/g) from DHASCO® (MATK-90). A 90-day subchronic safety study with a one-month recovery period using Sprague–Dawley rats included clinical observations, ophthalmic examination, hematology, clinical chemistry, toxicokinetic evaluation, and pathological assessments. Effects of MATK-90 were compared with those produced from DHASCO® and control (corn oil). Doses of MATK-90 (1.3, 2.5 and 5.0 g/kg/day) and DHASCO® (5.0 g/kg/day = 2 g of DHA) were administered once-daily by oral gavage at a volume of 10 mL/kg. The corn oil was also administered by oral gavage (10 mL/kg/day). There were no treatment-related adverse effects in any of the parameters measured at doses of ⩽2.5 g/kg/day of MATK-90 or at 5.0 g/kg/day of DHASCO®. In the mesenteric lymph node, marked macrophage infiltration was observed in 3 of 19 animals in the 5.0 g/kg/day MATK-90 treatment group and was considered to be adverse. The no-observable-adverse-effect level (NOAEL) for MATK-90 under the conditions of this study was 2.5 g/kg/day.