A subchronic toxicity study, preceded by an in utero exposure phase, with refined arachidonic acid-rich oil (RAO) derived from Mortierella alpina XM027 in rats

To evaluate the potential toxicity of refined arachidonic acid-rich oil (RAO) derived from Mortierella alpina (M. alpina) XM027, we performed a 90-day subchronic study in F-1 Sprague Dawley (SD) rats. This study was preceded by a 4-week pretreatment period of parental (F-0) rats and exposure of the F-0 dams throughout mating, gestation, and lactation. The results indicated that RAO, at dose levels of 0.5%, 1.5%, and 5%, did not affect either reproductive performance of the parental rats, or any characteristics of the pups. In the subchronic study with the offspring (F-1) rats, no treatment related abnormalities were observed. In summary, no observable adverse effect level (NOAEL) in this study was placed at 5% RAO, the highest level tested. This level corresponds to approximately 3750 mg/kg in F-0 females, 2850 mg/kg in F-0 males, 4850 mg/kg in F-1 females, and 4480 mg/kg in F-1 males. (C) 2014 Elsevier Inc. All rights reserved.