Safety assessment of DHA-rich microalgae from Schizochytrium sp - I. Subchronic rat feeding study

The purpose of this study was to determine the potential toxicity of docosa hexaenoic acid-rich microalgae from Schizochytrium sp. (DPM), administered in the diet to rats for at least 13 weeks. DRM was administered in the diet to groups of 20 male and 20 female Sprague-Dawley derived rats (CrI:CD(SD) BR) to provide dosages of 0, 400, 1500, and 4000 mg/kg/day for at least 13 weeks. DRM contained high levels of fat (approximately 41% w/w) of which lo ng-chain highly unsaturated fatty acids (PUFAs) were a major component. Vit amin E acetate was added to DRM at manufacture to provide supplementary die tary antioxidant given the highly unsaturated fat content of DRM. Untreated controls received the basal diet only. An additional group of 20 males and 20 females received basal diet mixed with fish oil (Arista) to provide a t arget dosage of 1628 mg/kg/day, an amount of fat comparable to that receive d by rats administered the highest dose of DRM. Vitamin E acetate was also added to the fish oil to provide a comparable level of dietary antioxidant provided to high-dose DRM rats. There were no treatment-related effects in clinical observations, body weights or weight gains, food consumption, hema tologic or urinalysis values, gross necropsy findings, or organ weights and there were no deaths. The only treatment-related changes in clinical chemi stry parameters were decreases in high-density lipoproteins and cholesterol in the DRM and fish oil groups when compared to the untreated controls. Th ese changes were expected based on the high PUFA content of DRM and fish oi l. There were no microscopic findings suggestive of toxicity. Periportal he patocellular fat vacuolation (accumulation of fat) was observed only in the livers of female rats in both the DRM (all dosages) and fish oil groups. T his finding was expected given the higher fat content of both the DRM and t he fish oil diets compared to the basal diet fed to the untreated controls. A slight increase in the incidence, but not severity, of cardiomyopathy wa s observed only in the 4000 mg/kg/day DRM males. This finding was not consi dered adverse because cardiomyopathy occurs spontaneously in rats and espec ially male rats of the Sprague-Dawley strain when fed high levels of fat. S ince cardiomyopathy does not develop in other species including primates fe d high-fat diets, its occurrence in rats is considered to have little relev ance to human health. This study demonstrates that administration of DRM di d not produce any treatment-related adverse effects in Sprague-Dawley rats of relevance to humans at dosages up to 4000 mg/kg/day for 13 weeks. (C) 20 01 Academic Press.