Evaluation of immunologic and intestinal effects in rats administered an E 171-containing diet, a food grade titanium dioxide (TiO2)

Lance K Blevins; Robert B Crawford; Anthony Bach; Michael D Rizzo; Jiajun Zhou; Joseph E Henriquez; D M Isha Olive Khan; Sera Sermet; Lora L Arnold; Karen L Pennington; Nathalia P Souza; Samuel M Cohen; Norbert E Kaminski

doi:10.1016/j.fct.2019.110793

Evaluation of immunologic and intestinal effects in rats administered an E 171-containing diet, a food grade titanium dioxide (TiO₂)

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

Authors

Affiliations

¹ Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
² Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Center for Research on Ingredient Safety, Michigan State University, East Lansing, MI, USA.
³ Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Cell and Molecular Biology Program, Michigan State University, East Lansing, MI, USA.
⁴ Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, USA.
⁵ Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
⁶ University of Nebraska Medical Center, Omaha, NE, USA.
⁷ University of Nebraska Medical Center, Omaha, NE, USA; Havlik-Wall Professor of Oncology, USA.
⁸ Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Center for Research on Ingredient Safety, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. Electronic address: kamins11@msu.edu.

Abstract

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 T_reg 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*

Substances

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

Grants and funding

P30 CA036727/CA/NCI NIH HHS/United States