Subchronic toxicity of fish oil concentrates in male and female rats.

There are an overwhelming number of reports indicating the beneficial effects of fish oil supplements in human and animal nutrition. The purpose of this study, second in a series, was to evaluate the effects, particularly those that may be harmful, of high-dose, long-term consumption of fish oil concentrates (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 were corn oil, pure menhaden oil (MO), pure MaxEPA fish oil or different mixtures of corn oil with MO. The stability and the homogeneity of the dosing solutions were tested under study conditions. The animals received isocaloric and isonitrogenous diets throughout. Food and pure water were supplied ad libitum. At the end of the in-life phase of the study, the animals were anaesthetized with CO2 and humanely killed by exsanguination. Blood and other tissues were prepared for various clinical, histopathological and laboratory tests. Some beneficial effects of FOC, such as reduction in total serum cholesterol, in rats were confirmed. However, we also observed a significant 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 FOC. High doses of FOC (5 mL/kg/d) reduced serum iron and vitamin E concentrations. A reduction in osmotic fragility of RBC as well as an increase in RBC deformity were also observed in rats treated with high doses of FOC. These rats showed a significant overall increase in WBC count. We conclude that in rats, subchronic consumption of high levels of FOC can be beneficial but may also be harmful because of induction of clinical abnormalities including increased red cell deformity, increased relative liver and spleen weights, and reduced serum HDL, iron and vitamin E concentrations.

Effect of subchronic dietary administration of butylated hydroxyanisole on canine stomach and hepatic tissue.

Beagle dogs, 29 males and 30 females, were assigned to feeding groups of 0, 1.0 and 1.3% butylated hydroxyanisole (BHA) for 180 days. Animals were observed daily for physical signs of pharmacological or toxicological effect. Except for the production of a reddish-brown urine, no physical signs attributable to BHA administration were observed. Both food consumption and body-weight gain were reduced in the BHA-treated animals. Fifty-one animals completed the study. At termination, tissues were examined for gross BHA-related effects, and specimens were taken for enzyme analysis, light microscopy, electron microscopy and morphometric analysis. The liver showed a significant weight increase over the control in both sexes at both BHA dose levels. Ultrastructural examination of the liver of BHA-treated animals revealed proliferation of smooth endoplasmic reticulum and hepatocytic cytoplasmic myelinoid bodies. Enzyme analysis of hepatic tissue showed a significant increase in mixed-function oxidases, UDP glucuronyl transferase, glutathione S-transferase and epoxide hydratase in the BHA-treated dogs compared with the controls. Light microscopy revealed no proliferative/hyperplastic lesions of the stomach/gastric epithelium. Electron microscopic examination of the lower oesophagus and stomach specimens from representative animals from each treatment group failed to reveal any treatment-related effect as compared with controls.