Safety assessment of DHA-rich microalgae from Schizochytrium sp - II. Developmental toxicity evaluation in rats and rabbits

Schizochytrium sp. (DRM) contains oil rich in highly unsaturated fatty acid s (PUFAs). Docosahexaenoic acid (DHA) is the most abundant PUFA component o f the oil (approx, 35% w/w). DHA-rich extracted oil from Schizochytrium sp. is intended for use as a nutritional ingredient in foods. As part of a com prehensive safety assessment program, the developmental toxicity of DRM was assessed in Sprague-Dawley derived rats [25/group, provided DRM in the die t at 0.6, 6, and 30% on gestation days (GD) 6-15] and in New Zealand White (NZW) rabbits (22/group, dosed with DRM at levels of 180, 600, and 1800 mg/ kg/day by oral gavage on GD 6-19). Fish oil was used as a negative control at dose levels to provide an equivalent amount of fat to that received by t he high-dose DRM rabbits. Maternal food consumption, body weights, and clin ical signs were recorded at regular intervals throughout these studies. Ani mals were sacrificed on GD 20 (rats) and GD 29 (rabbits) and examined for i mplant status, fetal weight, sex, and morphologic development. No clinical signs of toxicity were observed. Maternal exposure to DRM during organogene sis did not adversely affect the frequency of postimplantation loss, mean f etal body weight/litter, or external, visceral, or skeletal malformations i n either the rat or the rabbit. In the rats, neither maternal nor developme ntal toxicity was observed at any dietary concentration of DRM. Thus, 22 g/ kg/day(1) of DRM administered in the feed to pregnant rats during organogen esis was the NOEL (no-observed-effect level) for both maternal and developm ental toxicity. In rabbits, no maternal toxicity was expressed at DRM dose levels of 180 and 600 mg/kg/day. As a possible consequence of the high-fat content of the fish oil and DRM, reductions in food consumption and body we ight gain and a slight increase in abortions occurred in the fish oil contr ol and 1800 mg/kg/day DRM groups. Developmental toxicity was not observed a t any DRM dose level. Based on the results of this study, the NOEL for mate rnal toxicity of DRM was 600 mg/kg/day, and the NOEL for developmental toxi city was 1800 mg/kg/day in NZW rabbits. (C) 2001 Academic Press.