title: Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month toxicity study in dogs.
abstract: DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic acid manufactured from the microalgal oil. The objective of the 9-month study was to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000 and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any findings after a 2-month recovery period. DHA-EE was well tolerated at all doses. There were observations of dry flaky skin with occasional reddened areas at doses ≥1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no longer present after the recovery period. There were no toxicologically relevant findings in body weights, body weight gains, food consumption, ophthalmological examinations, and ECG measurements. Test article-related changes in hematology parameters were limited to decreases in reticulocyte count in the high-dose males and considered non-adverse. In clinical chemistry parameters, dose-related decreases in cholesterol and triglycerides levels were observed at all doses in males and females and attributed to the known lipid-lowering effects of DHA. There were no effects on other clinical chemistry, urinalysis or coagulation parameters. There were no abnormal histopathology findings attributed to test article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000 mg/kg bw/day for both genders.
authors.affiliation: DSM Nutritional Products, 6480 Dobbin Rd., Columbia, MD 21045, USA. Electronic address: Irina.dahms@dsm.com.
authors.forename: Irina
authors.initials: I
authors.lastname: Dahms
authors.affiliation: DSM Nutritional Products, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Beilstein
authors.affiliation: Charles River Laboratories Preclinical Services, Spencerville, OH 45887, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bonnette
authors.affiliation: DSM Nutritional Products, 6480 Dobbin Rd., Columbia, MD 21045, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects*; D012156:Reticulocytes / Q000187:drug effects; D012871:Skin Diseases / Q000139:chemically induced; D018675:Toxicity Tests / Q000379:methods*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D004281:Docosahexaenoic Acids; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D002784:Cholesterol
keywords: Algal oil; DHA ethyl ester; Docosahexaenoic acid; Dogs; Safety