Cytotoxicity, organ distribution and morphological effects of melamine and cyanuric acid in rats

Melamine (Mel) is used widely as a basic organic chemical intermediate in several products. Within the last 10 years there have been two high-profile Mel exposures that caused toxicological concern, especially regarding food adulteration. Objective: This study aimed to determine the toxicity of Mel and one of its homologs, cyanuric acid (Cya), in vitro and in vivo. Materials and Methods: The IC50 of Mel and Cya was determined by the MTT assay in NRK-52E and 293T cell lines. Organ-specific toxicity was assessed using the following dosing paradigm of Wistar rats: group 1: normal saline; group 2: Mel (180mg/kg); group 3: Cya (150mg/kg); and group 4: Mel (180mg/kg) +Cya (150mg/kg). Results: The NRK cell toxicity studies on Mel and Cya revealed IC50 values of 1.89 mg/mL and 4.20 mg/mL, respectively. Similarly, Mel and Cya IC50 values in 293T cells were 2.07 mg/mL and 3.71 mg/mL, respectively. Histopathologic studies revealed crystals in the renal medulla-cortex and loss of chief cells in the lining of the stomach in the group receiving Mel plus Cya. HPLC-MS analysis of organ homogenates showed that the concentration of Mel was greatest in the animals receiving a combination of both Mel and Cya. Discussion and conclusion: Mel is more toxic than its homolog Cya. The kidney is the most affected organ. Mel was present at high concentration not only in the kidneys, but also in the uterus and liver, informing the scope of future studies on the mechanism of Mel and Cya toxicity.