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 acids (PUFAs). Docosahexaenoic acid (DHA) is the most abundant PUFA component of 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 comprehensive safety assessment program, the developmental toxicity of DRM was assessed in Sprague–Dawley derived rats [25/group, provided DRM in the diet 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 the high-dose DRM rabbits. Maternal food consumption, body weights, and clinical signs were recorded at regular intervals throughout these studies. Animals were sacrificed on GD 20 (rats) and GD 29 (rabbits) and examined for implant status, fetal weight, sex, and morphologic development. No clinical signs of toxicity were observed. Maternal exposure to DRM during organogenesis did not adversely affect the frequency of postimplantation loss, mean fetal body weight/litter, or external, visceral, or skeletal malformations in either the rat or the rabbit. In the rats, neither maternal nor developmental toxicity was observed at any dietary concentration of DRM. Thus, 22 g/ kg/day1 of DRM administered in the feed to pregnant rats during organogenesis was the NOEL (no-observed-effect level) for both maternal and developmental 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 weight gain and a slight increase in abortions occurred in the fish oil control and 1800 mg/kg/day DRM groups. Developmental toxicity was not observed at any DRM dose level. Based on the results of this study, the NOEL for maternal toxicity of DRM was 600 mg/kg/day, and the NOEL for developmental toxicity was 1800 mg/kg/day in NZW rabbits.