Two-generation reproductive and developmental toxicity assessment of dietary N-acetyl-L-aspartic acid in rats

N-acetyl-l-aspartic acid (NAA) is a component of the mammalian central nervous system (CNS) that has also been identified in a number of foods. This paper reports the outcome of a reproductive toxicology study conducted with NAA in Sprague–Dawley® rats. NAA was added to diets at target doses of 100, 250 and 500 mg/kg of body weight/day and administered for two consecutive generations. A carrier control group was administered diet with no added NAA and a comparative control group was given aspartate (ASP), the constituent amino acid of NAA, at a target dose of 500 mg/kg of body weight/day. The study evaluated OECD 416 reproductive performance variables and additional segments to assess potential developmental effects, neurobehavioural and ophthalmologic function, and the concentrations of NAA or ASP in brain and plasma. No biologically significant differences were observed in any reproductive response variables, neurobehavioural tests, ophthalmologic examinations, body weights, feed consumption, or organ weights. Further, no test substance related mortalities or adverse clinical, neurohistopathologic or histopathologic findings were observed. Under the conditions of this study, the highest target dose of NAA, 500 mg/kg of body weight/day, represents the no-observed-adverse-effect-level (NOAEL) for reproductive and systemic toxicity, and neurotoxicity for Sprague–Dawley® rats.