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Table 3 Impact of TiO2 particles on intestinal mucusa

From: Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer

Study

Test system

Exposure conditions: dose range and exposure time

Material

Dispersion procedure

Main conclusions

Urrutia-Ortega et al., 2016 [96]

Oral gavage, mice. Wild-type or model of CAC via AOM/DSS induction.

5 mg/kg body weight/5 days/10 weeks

E171

Sonication for 30 min in water

Reduced number of goblet cells in the distal colon, in both groups (WT and CAC), higher decrease in the CAC model.

Talbot et al., 2018 [94]

HT29-MTX and in vivo rat acute and sub-chronic oral exposure

In vitro: 250 μg/mL; in vivo acute (7 days, daily gavage): 10 mg/kg bw/day; in vivo sub-chronic (60 days, drinking water): 10 and 0,1 mg/kg bw/day

E171 and P25 (anatase/rutile, 21 nm)

Probe sonication in 0,05% water/BSA 27 min

Penetration of TiO2 into the mucoid area of HT29-MTX cells (patchy structures of mucus). When E171 and P25 were administered in vivo, cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged

Dorier et al., 2019 [95]

Caco-2/HT29-MTX co-culture

Acute (6-48 h; 50 μg/mL) or repeated twice a week for 3 weeks; 10 and 50 μg/mL)

E171, anatase 12 nm (A12), anatase/rutile, 21 nm (P25)

Indirect cup-type sonication (high energy) 30 min in water

No impact on cell differentiation. Inflammatory profile (chronic and acute), increased mucus secretion (chronic). Epithelial integrity unaltered, content of ABC family of xenobiotic efflux pumps modified (either increased or decreased depending on the particle: decreased with E171, increased with P25).

Pinget et al., 2019 [133]

Mice, drinking water

2, 10, 50 mg TiO2/kg b.w./day for 21 days

E171

Suspension in drinking water

Decreased Muc2 gene expression in the colon at 10 and mg/kg b.w./day

Medina-Reyes et al., 2020 [88]

Mice with either high fat diet (HFD) or regular diet (RD)

5 mg/kg b.w. for 16 weeks

E171

Suspension in drinking water

Hyperplasia and hypertrophy of goblet cells; increased Muc2, Muc5AC, Muc1 and Muc13 mRNA expression.

  1. aAbbreviations: ABC ATP-binding cassette, AOM azoxymethane, BSA bovine serum albumin, CAC model of colitis-associated cancer, DSS dextran sulfate sodium, WT wild-type