Safety Assessment of Dodecanedioic Acid (Dodecanedioic Acid Disodium Salt) Using Genotoxicity and Repeated 28-day Oral Toxicological Evaluation

To evaluate the safety of Metabolyte™ (sodium dodecanedioate) for human consumption, results from <i>in vitro</i> and <i>in vivo</i> studies are reported, including a bacterial reverse mutation assay, an <i>in vitro</i> mammalian chromosome aberration test, an <i>in vivo</i> mammalian bone marrow micronucleus test, an <i>in vivo</i> mammalian bone marrow chromosome aberration test, and a 28-day repeat-dose oral toxicological evaluation. Metabolyte™ was not mutagenic in the <i>in vitro</i> and <i>in vivo</i> studies. In the 28-day study, Wistar rats were administered Metabolyte™ by gavage at doses of 0 (G1), 3250 (G2), 6500 (G3), and 13,100 (G4) mg test article/kg bw/day. Histological examination did not reveal any test item related lesions. In the G3 and G4 dose groups, significantly altered electrolyte levels and decrease in sodium and chloride levels in males, and increase in calcium and phosphorous in females, are indicative of possible kidney malfunction. The observed significant increase in triglycerides in G4 males and G3 and G4 females and bile acid in G3 and G4 males and G4 females, decrease in globulin and concurrent increase in albumin/globulin ratio in G4 males, and increase/decrease in ALT in G4 males and females indicate liver malfunction. Significant alterations in motor activity were observed, along with an increase in alkaline phosphatase, in G3 and G4 female animals. Significant changes in absolute relative weight of kidney and liver were detected in G4 females. The NOAEL was considered to be 3250 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female rats.