Immunotoxic effects of the color additive caramel color III: immune function studies in rats

Fundam Appl Toxicol. 1993 Jan;20(1):30-7. doi: 10.1006/faat.1993.1004.


Administration of the color additive caramel color III (AC) may cause a reduction in total white blood cell counts in rats due to reduced lymphocyte counts. Beside lymphopenia, several other effects in rat have been described. The effects are caused by the imidazole derivative 2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) and occur in rats fed a diet low in vitamin B6. In the present paper, immune function studies on AC and THI with rats fed a diet low, but not deficient in vitamin B6 are presented and discussed. Rats were exposed to 0.4 or 4% AC or to 5.72 ppm THI in drinking water during and for 28 days prior to the start of immune function assays. Resistance to Trichinella spiralis was examined in an oral infection model and clearance of Listeria monocytogenes upon an intravenous infection was studied. In addition, natural cell-mediated cytotoxicity of splenic and nonadherent peritoneal cells and the antibody response to sheep red blood cells were studied. From the results it is concluded that exposure of rats to AC or THI influenced various immune function parameters. Thymus-dependent immunity was suppressed, while parameters of the nonspecific resistance were also affected, as shown by a decreased natural cell-mediated cytotoxicity in the spleen and an enhanced clearance of L. monocytogenes.

MeSH terms

  • Animals
  • Antibody Formation / drug effects
  • Candy
  • Carbohydrates
  • Cell Adhesion
  • Erythrocytes / immunology
  • Food Coloring Agents / toxicity*
  • Imidazoles / pharmacology
  • Immunity / drug effects*
  • Immunity, Cellular / drug effects
  • Immunosuppressive Agents / pharmacology
  • Leukocyte Count
  • Listeriosis / immunology
  • Lymphocytes / immunology
  • Male
  • Organic Chemicals
  • Rats
  • Rats, Wistar
  • Trichinellosis / immunology
  • Vitamin B 6 Deficiency / immunology


  • Carbohydrates
  • Food Coloring Agents
  • Imidazoles
  • Immunosuppressive Agents
  • Organic Chemicals
  • caramel coloring
  • 2-acetyl-4(5)-tetrahydroxybutylimidazole