Risk assessment for the combinational effects of food color additives: neural progenitor cells and hippocampal neurogenesis

J Toxicol Environ Health A. 2009;72(21-22):1412-23. doi: 10.1080/15287390903212816.


In 2006, the Korea Food and Drug Administration reported that combinations of dietary colors such as allura red AC (R40), tartrazine (Y4), sunset yellow FCF (Y5), amaranth (R2), and brilliant blue FCF (B1) are widely used in food manufacturing. Although individual tar food colors are controlled based on acceptable daily intake (ADI), there is no apparent information available for how combinations of these additives affect food safety. In the current study, the potencies of single and combination use of R40, Y4, Y5, R2, and B1 were examined on neural progenitor cell (NPC) toxicity, a biomarker for developmental stage, and neurogenesis, indicative of adult central nervous system (CNS) functions. R40 and R2 reduced NPC proliferation and viability in mouse multipotent NPC, in the developing CNS model. Among several combinations tested in mouse model, combination of Y4 and B1 at 1000-fold higher than average daily intake in Korea significantly decreased numbers of newly generated cells in adult mouse hippocampus, indicating potent adverse actions on hippocampal neurogenesis. However, other combinations including R40 and R2 did not affect adult hippocampal neurogenesis in the dentate gyrus. Evidence indicates that single and combination use of most tar food colors may be safe with respect to risk using developmental NPC and adult hippocampal neurogenesis. However, the response to excessively high dose combination of Y4 and B1 is suggestive of synergistic effects to suppress proliferation of NPC in adult hippocampus. Data indicated that combinations of tar colors may adversely affect both developmental and adult hippocampal neurogenesis; thus, further extensive studies are required to assess the safety of these additive combinations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dentate Gyrus / cytology*
  • Diet
  • Food Coloring Agents / administration & dosage*
  • Food Coloring Agents / toxicity*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Multipotent Stem Cells / drug effects*
  • Neurons / drug effects*
  • Risk Factors


  • Food Coloring Agents