Evaluation of immunologic and intestinal effects in rats administered an E 171-containing diet, a food grade titanium dioxide (TiO 2)

Food Chem Toxicol. 2019 Nov;133:110793. doi: 10.1016/j.fct.2019.110793. Epub 2019 Aug 29.


The toxicity of dietary E 171, a food grade titanium dioxide was evaluated. A recent study reported rats receiving E 171 in water developed inflammation and aberrant crypt foci (ACF) in the gastrointestinal tract. Here, rats received food containing E 171 (7 or 100 days). The 100-day study included feeding E 171 after dimethylhydrazine (DMH) or vehicle only pretreatment. Food consumption was similar between treatment groups with maximum total cumulative E 171 exposure being 2617 mg/kg in 7 days and 29,400 mg/kg in 100 days. No differences were observed due to E 171 in the percentage of dendritic, CD4+ T or Treg cells within Peyer's patches or the periphery, or in cytokine production in plasma, sections of jejunum, and colon in 7- or 100-day E 171 alone fed rats. Differences were observed for IL-17A in colon (400 ppm E 171 + DMH) and IL-12p70 in plasma (40 ppm E 171 + DMH). E 171 had no effect on histopathologic evaluations of small and large intestines, liver, spleen, lungs, or testes, and no effects on ACF, goblet cell numbers, or colonic gland length. Dietary E 171 administration (7- or 100-day), even at high doses, produced no effect on the immune parameters or tissue morphology.

Keywords: Dietary titanium dioxide; E 171; Gastrointestinal inflammation; Intestinal carcinogenesis; T(regulatory) cells.

MeSH terms

  • 1,2-Dimethylhydrazine / pharmacology
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • Carcinogenesis / drug effects
  • Carcinogens / pharmacology
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Food Additives / chemistry
  • Food Additives / toxicity*
  • Intestinal Mucosa / drug effects*
  • Male
  • Particle Size
  • Peyer's Patches / drug effects
  • Rats, Wistar
  • T-Lymphocytes, Regulatory / drug effects
  • Titanium / chemistry
  • Titanium / toxicity*


  • Carcinogens
  • Cytokines
  • Food Additives
  • titanium dioxide
  • Titanium
  • 1,2-Dimethylhydrazine