Subchronic toxicity of fish oil concentrates in male and female rats

There are an overwhelming number of reports indicating the beneficial effec ts of fish oil supplements in human and animal nutrition. The purpose of th is study, second in a series, was to evaluate the effects, particularly tho se that may be harmful, of high-dose, long-term consumption of fish oil con centrates (FOC) using male and female rats. One hundred and twenty male and 120 female rats were gavaged daily with oils and oil mixtures in a volume equal to 0.5% body weight (5 mL/kg/d) for 13 weeks. The administered oils w ere corn oil, pure menhaden oil (MO), pure MaxEPA(R) fish oil or different mixtures of corn oil with MO. The stability and the homogeneity of the dosi ng solutions were tested under study conditions. The animals received isoca loric and isonitrogenous diets throughout. Food and pure water were supplie d ad libitum. At the end of the in-life phase of the study, the animals wer e anaesthetized with CO2 and humanely killed by exsanguination. Blood and o ther tissues were prepared for various clinical, histopathological and labo ratory tests. Some beneficial effects of FOC, such as reduction in total se rum cholesterol, in rats were confirmed. However, we also observed a signif icant reduction in absolute amount of serum HDL and a significant increase in relative liver and spleen weights in both sexes with the high dose of FO C. High doses of FOC (5 mL/kg/d) reduced serum iron and vitamin E concentra tions. A reduction in osmotic fragility of RBC as well as an increase in RB C deformity were also observed in rats treated with high doses of FOC. Thes e rats showed a significant overall increase in WBC count. We conclude that in rats, subchronic consumption of high levels of FOC can be beneficial bu t may also be harmful because of induction of clinical abnormalities includ ing increased red cell deformity, increased relative liver and spleen weigh ts, and reduced serum HDL, iron and vitamin E concentrations.