ABSTRACT
ARASCO and DHASCO oils are microbially-derived triglycerides rich in arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids, respectively. Both oils were tested for mutagenic activity in three different in vitro mutagenesis assays. All assays were conducted with and without metabolic activation. Neither ARASCO nor DHASCO oil was mutagenic in the Ames reverse mutation assay using five different Salmonella histidine auxotroph tester strains, nor were the oils mutagenic in the mouse lymphoma TK(+/-) forward mutation assay. The oils showed no clastogenic activity in chromosomal aberration assays performed with Chinese hamster ovary cells. Based on these assays, neither ARASCO nor DHASCO oils appear to have any genotoxic potential.
Subject(s)
Arachidonic Acid/toxicity , Docosahexaenoic Acids/toxicity , Mutagens/toxicity , Animals , Arachidonic Acid/analysis , CHO Cells , Cell Survival/drug effects , Chromosome Aberrations , Chromosomes/drug effects , Cricetinae , DNA/drug effects , Docosahexaenoic Acids/analysis , Leukemia L5178/enzymology , Leukemia L5178/genetics , Leukemia L5178/pathology , Mice , Mutagenicity Tests , Oils/chemistry , Oils/toxicity , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Tumor Cells, CulturedABSTRACT
The long-chain omega-3 and omega-6 fatty acids, docosahexaenoic and arachidonic acids, are important in fetal development, but may be depleted from the mother during pregnancy as she transfers reserves to the developing fetus in utero and later to the infant through her breast milk. Pregnant women can increase their dietary intake of these nutrients to maintain adequate maternal reserves and ensure an optimal infant supply. DHASCO(R) and ARASCO(R) oils, concentrated sources of docosahexaenoic and arachidonic acids, respectively, have been tested in acute and subchronic studies without toxic effects. The present developmental toxicity study was undertaken to test for potential teratogenic activity of these oils to ensure their safe use during pregnancy. DHASCO and ARASCO oils were administered by oral gavage to pregnant rats at doses up to 1250 and 2500 mg/kg body weight/day, respectively, during the period of organogenesis. Caesarean sections and necropsies were performed on day 20 of gestation. Maternal reproductive outcomes were analyzed, and fetal external, soft and skeletal tissue were examined. Treatment with these oils did not produce overt maternal toxicity, nor did either oil result in changes in pre- or postimplantation losses, resorptions, live births or sex ratios. Neither oil caused fetal malformations. Increased frequencies of renal variations in development occurred in a non-dose-dependent manner and were not toxicologically significant. We conclude that these oils are not teratogenic at doses that represent a 100-fold safety factor over expected use levels.
Subject(s)
Arachidonic Acid/pharmacology , Docosahexaenoic Acids/pharmacology , Embryonic and Fetal Development/drug effects , Animals , Body Weight/drug effects , Feeding Behavior , Female , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
Docosahexaenoic acid (DHA), a 22-carbon long-chain polyunsaturated fatty acid of the omega-3 family, is a major structural component of neural membranes and is a particularly important nutrient during infant development. New safe and well-defined sources of DHA are required for infant formula fortification and dietary supplementation. DHASCO oil is an algal-derived triglyceride containing 40-50% DHA. Previous studies have shown that DHASCO oil is neither mutagenic nor toxic in acute or 28-day subchronic tests. To further establish the safety of this oil, a 90-day subchronic toxicity study in rats which included haematology, clinical chemistry, pathology and ophthalmologic, neurobehavioural and neuropathological assessments, using doses of 0.5 and 1.25g/kg body weight/day was performed. There were no treatment-related adverse effects in any of the parameters measured at either dose. Based on these results, the no-adverse-effect level (NOAEL) for DHASCO oil under the conditions of this study corresponds to the highest dose level. The DHA in the DHASCO oil was bioavailable, resulting in significant elevations in the levels of this fatty acid in liver, heart and brain after 90 days of administration. In conclusion, this 90-day subchronic toxicity study provides additional evidence that DHASCO oil is a safe and bioavailable source of dietary DHA.
Subject(s)
Docosahexaenoic Acids/adverse effects , Triglycerides/adverse effects , Animals , Biological Availability , Dietary Fats , Docosahexaenoic Acids/pharmacokinetics , Dose-Response Relationship, Drug , Female , Humans , Infant Food , Infant, Newborn , Male , Mutagenesis , No-Observed-Adverse-Effect Level , Rats , Toxicity Tests , Triglycerides/pharmacokineticsABSTRACT
Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P<0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of omega-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of omega-6 polyunsaturated fatty acids.
