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

Toxicol Mech Methods. 2016 Sep;26(7):501-510. doi: 10.1080/15376516.2016.1201559. Epub 2016 Jul 17.

Abstract

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 (180 mg/kg); group 3: Cya (150 mg/kg); and group 4: Mel (180 mg/kg) + Cya (150 mg/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.

Keywords: Cyanuric acid; ELISA; high performance liquid chromatography–tandem mass spectrometry; melamine; melamine cyanurate.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Gastric Mucosa / metabolism
  • Genitalia / drug effects*
  • Genitalia / metabolism
  • Genitalia / pathology
  • HEK293 Cells
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Organ Specificity
  • Rats, Wistar
  • Stomach / drug effects*
  • Stomach / pathology
  • Tissue Distribution
  • Triazines / pharmacokinetics
  • Triazines / toxicity*

Substances

  • Triazines
  • cyanuric acid
  • melamine