90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil

Food Chem Toxicol. 2009 Oct;47(10):2407-18. doi: 10.1016/j.fct.2009.06.036. Epub 2009 Jul 1.

Abstract

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.

MeSH terms

  • Animals
  • Arachidonic Acid / classification
  • Arachidonic Acid / metabolism
  • Arachidonic Acid / toxicity*
  • CHO Cells
  • Cell Line, Tumor
  • Chromosome Aberrations / chemically induced
  • Cricetinae
  • Cricetulus
  • Dietary Fats, Unsaturated / classification
  • Dietary Fats, Unsaturated / metabolism
  • Dietary Fats, Unsaturated / toxicity*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Female
  • Leukemia L5178 / drug therapy
  • Leukemia L5178 / enzymology
  • Leukemia L5178 / genetics
  • Male
  • Maternal Exposure / adverse effects*
  • Monocytes / drug effects*
  • Monocytes / pathology
  • Mutagenicity Tests
  • Mutagens / classification
  • Mutagens / metabolism
  • Mutagens / toxicity*
  • No-Observed-Adverse-Effect Level
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Wistar
  • Reproduction / drug effects*
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism

Substances

  • Dietary Fats, Unsaturated
  • Mutagens
  • Arachidonic Acid
  • Thymidine Kinase
  • thymidine kinase 1