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

Abstract

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=2g 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 <or= 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.