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

• Published in: Food and chemical toxicology 2010-10, Vol.48 (10), p.2778-2784
• Main Authors: Hadley, K.B., Ryan, A.S., Nelson, E.B., Salem, N.
• Format: Article
• Language: English
• Subjects: Animals; Area Under Curve; Assessments; Biological and medical sciences; Body Weight - drug effects; Corn oil; Corn Oil - analysis; Dietary Supplements - toxicity; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacokinetics; Docosahexaenoic Acids - toxicity; Eating - drug effects; Esters - pharmacokinetics; Esters - toxicity; Ethyl esters; Fatty Acids - analysis; Female; Infiltration; Lymph; Macrophages - drug effects; Male; Medical sciences; Microalgae - chemistry; No-Observed-Adverse-Effect Level; Organ Size - drug effects; Rats; Rats, Sprague-Dawley; Safety; Safety assessment; Single cell oil; Toxicity; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2010.07.006

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% (400–500mg/g) of DHA by weight. Martek Biosciences Corporation has developed a concentrated ethyl ester of DHA (900mg/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 5.0g/kg/day) and DHASCO® (5.0g/kg/day=2g of DHA) were administered once-daily by oral gavage at a volume of 10mL/kg. The corn oil was also administered by oral gavage (10mL/kg/day). There were no treatment-related adverse effects in any of the parameters measured at doses of ⩽2.5g/kg/day of MATK-90 or at 5.0g/kg/day of DHASCO®. In the mesenteric lymph node, marked macrophage infiltration was observed in 3 of 19 animals in the 5.0g/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 2.5g/kg/day.