90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil.
The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat feeding study with in utero exposure. The results of the genotoxicity assays were all negative. The in utero phase of the 90-day study involved dietary exposure to 0.5%, 1.5% and 5% RAO and two controls diets, a standard feed low-fat diet and a high-fat diet supplemented with 5% corn oil. This exposure covered four-weeks prior to mating, through mating, gestation and lactation until offspring (F(1)) weaning. A subsequent 90-day feeding study in the F(1) rats evaluated the same test and control diets. Statistically significant effects were seen for selected histopathology, clinical chemistry and organ weight endpoints; however, other than increased absolute and relative monocytes seen in both sexes of high-dose rats, the observations were not attributed to treatment for one or more reasons. Based on these findings, no adverse treatment-related effects for RAO were seen at up to 5% in the diet, equivalent to an overall average RAO intake of 3170 mg/kg bwt/day. These and similar findings for other refined ARA-rich oils establish a strong body of evidence for the safety of this RAO.
Casterton
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Cargill, Incorporated, Wayzata, MN 55391, USA. Phillip_Casterton@cargill.com
Curry
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Lina
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Wolterbeek
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Kruger
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D000818:Animals; D016718:Arachidonic Acid / Q000145:classification / Q000378:metabolism / Q000633:toxicity*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000139:chemically induced; D006224:Cricetinae; D003412:Cricetulus; D004042:Dietary Fats, Unsaturated / Q000145:classification / Q000378:metabolism / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005260:Female; D007940:Leukemia L5178 / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000145:classification / Q000378:metabolism / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D004042:Dietary Fats, Unsaturated; D009153:Mutagens; D016718:Arachidonic Acid; D013937:Thymidine Kinase; C092717:thymidine kinase 1