Table 2.
Basic characteristics and quality evaluation of the included studies on in vitro genotoxicity of TiO2 NPs 1.
Included Studies | Country | Test Cells and Exposure Methods | TiO2-NP Characteristics | Concentration (μg/mL) |
Exposure | Control | Reliability Evaluation | Correlation Evaluation | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Crystal | Size (nm) |
Purity (%) |
n | Mean ± SD | n | Mean ± SD | ||||||
Outcomes were described as T DNA% | ||||||||||||
Shukla R. K. 2011 [29] | India | Human epidermal cells line A431, exposed for 6 h | Anatase | 50 | 99.7 | 0.008 | 3 | 9.72 ± 0.78 | 3 | 9.36 ± 0.69 | high | B |
0.08 | 3 | 9.76 ± 0.40 | 3 | 9.36 ± 0.69 | ||||||||
0.8 | 3 | 11.79 ± 0.94 | 3 | 9.36 ± 0.69 | ||||||||
8 | 3 | 2.35 ± 0.43 | 3 | 9.36 ± 0.69 | ||||||||
80 | 3 | 12.89 ± 0.47 | 3 | 9.36 ± 0.69 | ||||||||
Hong L. 2011 [30] | China | Human lung adenocarcinoma cells, exposed for 6 h | NA | 5–10 | >99.9 | 25 | 25 | 9.94 ± 6.72 | 25 | 5.53 ± 3.70 | medium | A+++ |
50 | 25 | 14.26 ± 13.67 | 25 | 5.53 ± 3.70 | ||||||||
100 | 25 | 12.37 ± 5.16 | 25 | 5.53 ± 3.70 | ||||||||
200 | 25 | 9.47 ± 4.97 | 25 | 5.53 ± 3.70 | ||||||||
Shukla R. K. 2013 [31] | India | HepG2 human hepatocellular carcinoma cells, exposed for 6 h | Anatase | 30–70 | 99.7 | 1 | 3 | 8.61 ± 0.67 | 3 | 7.75 ± 0.36 | high | B |
10 | 3 | 9.13 ± 0.54 | 3 | 7.75 ± 0.36 | ||||||||
20 | 3 | 10.53 ± 0.49 | 3 | 7.75 ± 0.36 | ||||||||
40 | 3 | 11.61 ± 0.38 | 3 | 7.75 ± 0.36 | ||||||||
80 | 3 | 13.55 ± 0.43 | 3 | 7.75 ± 0.36 | ||||||||
Chen Z. 2014 [14] | China | V79 cells, exposed for 6 h, 24 h | Anatase | 75 ± 15 | 99.90 | 5 | 3 | 12.863 ± 11.00(6 h) 7.557 ± 6.846(24 h) |
3 | 11.836 ± 6.073(6 h) 6.000 ± 6.866(24 h) |
high | A+++ |
20 | 3 | 11.470 ± 8.074(6 h) 9.007 ± 10.417(24 h) |
3 | 11.836 ± 6.073(6 h) 6.000 ± 6.866(24 h) |
||||||||
100 | 3 | 12.094 ± 7.677(6 h) 9.005 ± 7.177(24 h) |
3 | 11.836 ± 6.073(6 h) 6.000 ± 6.866(24 h) |
||||||||
Frenzilli G. 2014 [32] | Italy | Human fibroblast (HuDE), exposed for 4 h, 24 h and 48 h | Anatase | 20–50 | 99.7 | 20 | 2 | 16.5 ± 1.9(4 h) 14.0 ± 3.7(24 h) 20.3 ± 5.3(48 h) |
2 | 12.1 ± 1.8(4 h) 13.7 ± 2.3(24 h) 20.3 ± 6.6(48 h) |
medium | B+ |
50 | 2 | 18.6 ± 3.3(4 h) 16.3 ± 5.7(24 h) 20.9 ± 1.7(48 h) |
2 | 12.1 ± 1.8(4 h) 13.7 ± 2.3(24 h) 20.3 ± 6.6(48 h) |
||||||||
100 | 2 | 23.4 ± 4.7(4 h) 17.3 ± 2.9(24 h) 21.0 ± 4.1(48 h) |
2 | 12.1 ± 1.8(4 h) 13.7 ± 2.3(24 h) 20.3 ± 6.6(48 h) |
||||||||
150 | 2 | 25.0 ± 2.6(4 h) 16.4 ± 8.6(24 h) 20.8 ± 6.7(48 h) |
2 | 12.1 ± 1.8(4 h) 13.7 ± 2.3(24 h) 20.3 ± 6.6(48 h) |
||||||||
Frenzilli G. 2014 [32] | Italy | Bottlenose dolphin fibroblast (BDF), exposed for 4 h, 24 h and 48 h | Anatase | 20–50 | 99.7 | 20 | 2 | 34.6 ± 10.5(4 h) 38.4 ± 2.5(24 h) 32.7 ± 14.8(48 h) |
2 | 22.6 ± 6.5(4 h) 17.6 ± 2.1(24 h) 13.5 ± 5.2(48 h) |
medium | B+ |
50 | 2 | 31.1 ± 8.0(4 h) 25.6 ± 5.1(24 h) 27.3 ± 9.3(48 h) |
2 | 22.6 ± 6.5(4 h) 17.6 ± 2.1(24 h) 13.5 ± 5.2(48 h) |
||||||||
100 | 2 | 34.8 ± 7.2(4 h) 21.9 ± 1.9(24 h) 25.2 ± 2.4(48 h) |
2 | 22.6 ± 6.5(4 h) 17.6 ± 2.1(24 h) 13.5 ± 5.2(48 h) |
||||||||
150 | 2 | 21.2 ± 9.6(4 h) 25.0 ± 0.1(24 h) 25.9 ± 7.6(48 h) |
2 | 22.6 ± 6.5(4 h) 17.6 ± 2.1(24 h) 13.5 ± 5.2(48 h) |
||||||||
Frenzilli G. 2014 [32] | Italy | Mouse fibroblast (3 T3), exposed for 4 h, 24 h and 48 h | Anatase | 20–50 | 99.7 | 20 | 2 | 24.4 ± 3.1(4 h) 21.4 ± 14.9(24 h) 18.3 ± 5.1(48 h) |
2 | 17.2 ± 4.2(4 h) 14.5 ± 2.7(24 h) 22.1 ± 5.3(48 h) |
medium | B+ |
50 | 2 | 21.8 ± 4.3(4 h) 26.0 ± 9.1(24 h) 28.3 ± 10.1(48 h) |
2 | 17.2 ± 4.2(4 h) 14.5 ± 2.7(24 h) 22.1 ± 5.3(48 h) |
||||||||
100 | 2 | 13.8 ± 2.7(4 h) 14.5 ± 4.8(24 h) 21.0 ± 3.9(48 h) |
2 | 17.2 ± 4.2(4 h) 14.5 ± 2.7(24 h) 22.1 ± 5.3(48 h) |
||||||||
150 | 2 | 18.8 ± 2.0(4 h) 15.9 ± 1.8(24 h) 26.3 ± 4.9(48 h) |
2 | 17.2 ± 4.2(4 h) 14.5 ± 2.7(24 h) 22.1 ± 5.3(48 h) |
||||||||
Frenzilli G. 2014 [32] | Italy | Human leukocytes (HL), exposed for 4 h, 24 h and 48 h | Anatase | 20–50 | 99.7 | 20 | 2 | 10.6 ± 4.5(4 h) 14.6 ± 5.9(24 h) 14.7 ± 3.2(48 h) |
2 | 8.3 ± 2.3(4 h) 11.8 ± 3.2(24 h) 10.0 ± 2.1(48 h) |
medium | B+ |
50 | 2 | 12.3 ± 4.4(4 h) 11.2 ± 2.5(24 h) 14.4 ± 7.8(48 h) |
2 | 8.3 ± 2.3(4 h) 11.8 ± 3.2(24 h) 10.0 ± 2.1(48 h) |
||||||||
100 | 2 | 13.2 ± 4.8(4 h) 13.1 ± 2.5(24 h) 12.6 ± 5.1(48 h) |
2 | 8.3 ± 2.3(4 h) 11.8 ± 3.2(24 h) 10.0 ± 2.1(48 h) |
||||||||
Frenzilli G. 2014 [32] | Italy | Bottlenose dolphin leukocytes (BDL), exposed for4 h, 24 h and 48 h | Anatase | 20–50 | 99.7 | 20 | 2 | 33.8 ± 15.1(4 h) 44.5 ± 22.6(24 h) 29.5 ± 9.7(48 h) |
2 | 25.5 ± 10.6(4 h) 35.2 ± 19.5(24 h) 36.1 ± 14.3(48 h) |
medium | B+ |
50 | 2 | 27.8 ± 7.8(4 h) 50.4 ± 19.4(24 h) 44.9 ± 18.8(48 h) |
2 | 25.5 ± 10.6(4 h) 35.2 ± 19.5(24 h) 36.1 ± 14.3(48 h) |
||||||||
100 | 2 | 35.3 ± 15.9(4 h) 47.5 ± 16.2(24 h) 43.9 ± 12.1(48 h) |
2 | 25.5 ± 10.6(4 h) 35.2 ± 19.5(24 h) 36.1 ± 14.3(48 h) |
||||||||
Demir E. 2015 [33] | Spain | Human embryonic kidney cells (HEK293), cultured for 1 h | Rutile | 21 | ≥99.5 | 10 | 4 | 14.11 ± 0.21 | 4 | 11.31 ± 0.67 | high | A |
100 | 4 | 15.11 ± 0.22 | 4 | 11.31 ± 0.67 | ||||||||
1000 | 4 | 32.21 ± 0.77 | 4 | 11.31 ± 0.67 | ||||||||
50 | ≥98 | 10 | 4 | 12.89 ± 0.75 | 4 | 11.31 ± 0.67 | ||||||
100 | 4 | 13.88 ± 0.65 | 4 | 11.31 ± 0.67 | ||||||||
1000 | 4 | 30.29 ± 0.67 | 4 | 11.31 ± 0.67 | ||||||||
Demir E. 2015 [33] | Spain | Mouse embryonic kidney cells (NIH/3 T3), cultured for 1 h | Rutile | 21 | ≥99.5 | 10 | 4 | 14.10 ± 0.27 | 4 | 12.31 ± 0.17 | high | A |
100 | 4 | 15.41 ± 0.29 | 4 | 12.31 ± 0.17 | ||||||||
1000 | 4 | 35.91 ± 0.57 | 4 | 12.31 ± 0.17 | ||||||||
50 | ≥98 | 10 | 4 | 12.10 ± 0.78 | 4 | 12.31 ± 0.17 | ||||||
100 | 4 | 13.59 ± 0.73 | 4 | 12.31 ± 0.17 | ||||||||
1000 | 4 | 31.77 ± 0.60 | 4 | 12.31 ± 0.17 | ||||||||
Kansara K. 2015 [34] | India | Human lung cancer cell line (A549), exposed for 6 h | Rutile | 4–8 | 99.7 | 25 | 3 | 5.14 ± 0.12 | 3 | 4.48 ± 0.11 | medium | B |
50 | 3 | 6.06 ± 0.15 | 3 | 4.48 ± 0.11 | ||||||||
75 | 3 | 8.25 ± 0.24 | 3 | 4.48 ± 0.11 | ||||||||
100 | 3 | 9.49 ± 0.25 | 3 | 4.48 ± 0.11 | ||||||||
Andreoli C. 2018 [35] | Italy | Peripheral blood monocytes, exposed for 24 h | Anatase | 20–60 | >99.5 | 10 | 4 | 1.14 ± 0.23 | 4 | 0.52 ± 0.12 | medium | A |
50 | 4 | 1.62 ± 0.47 | 4 | 0.52 ± 0.12 | ||||||||
100 | 4 | 2.01 ± 0.66 | 4 | 0.52 ± 0.12 | ||||||||
200 | 4 | 1.54 ± 0.52 | 4 | 0.52 ± 0.12 | ||||||||
Andreoli C. 2018 [35] | Italy | Peripheral blood monocytes, exposed for 24 h | Rutile | 30 × 100 | >99.5 | 10 | 4 | 1.19 ± 0.19 | 4 | 0.44 ± 0.05 | medium | A |
50 | 4 | 2.33 ± 0.68 | 4 | 0.44 ± 0.05 | ||||||||
100 | 4 | 2.62 ± 0.54 | 4 | 0.44 ± 0.05 | ||||||||
200 | 4 | 3.48 ± 1.59 | 4 | 0.44 ± 0.05 | ||||||||
Andreoli C. 2018 [35] | Italy | Peripheral blood monocytes, exposed for 24 h | Anatase/Rutile | 45–262 | >99.5 | 10 | 4 | 1.30 ± 0.04 | 4 | 0.34 ± 0.01 | medium | A |
50 | 4 | 2.51 ± 0.96 | 4 | 0.34 ± 0.01 | ||||||||
100 | 4 | 4.44 ± 0.18 | 4 | 0.34 ± 0.01 | ||||||||
200 | 4 | 4.45 ± 0.09 | 4 | 0.34 ± 0.01 | ||||||||
Osman I. F. 2018 [36] | UK | Lymphocytes from patients with respiratory diseases, exposed for 72 h | Anatase | 40–70 | 99.7 | 10 | 40 | 17.7 ± 5.4 | 40 | 15.4 ± 5.3 | high | B |
30 | 40 | 19.0 ± 5.5 | 40 | 15.4 ± 5.3 | ||||||||
50 | 40 | 23.3 ± 6.5 | 40 | 15.4 ± 5.3 | ||||||||
Osman I. F. 2018 [36] | UK | Lymphocytes from healthy people, exposed for 72 h | Anatase | 40–70 | 99.7 | 10 | 12 | 12.4 ± 6.1 | 12 | 10.2 ± 4.7 | high | B |
30 | 12 | 13.8 ± 5.5 | 12 | 10.2 ± 4.7 | ||||||||
50 | 12 | 15.3 ± 6.3 | 12 | 10.2 ± 4.7 | ||||||||
Outcomes were described as TL (μm) | ||||||||||||
Hong L. 2011 [30] | China | Human lung adenocarcinoma cells, exposed for 6 h | NA | 5–10 | >99.9 | 25 | 25 | 65.23 ± 26.86 | 25 | 37.50 ± 15.35 | medium | A+++ |
50 | 25 | 78.19 ± 37.43 | 25 | 37.50 ± 15.35 | ||||||||
100 | 25 | 69.54 ± 20.61 | 25 | 37.50 ± 15.35 | ||||||||
200 | 25 | 66.18 ± 17.87 | 25 | 37.50 ± 15.35 | ||||||||
Ünal F. 2021 [37] | Turkey | Human lymphocytes, exposed for 30 min | NA | <100 | NA | 20 | 3 | 51.60 ± 0.64 | 3 | 52.70 ± 0.55 | medium | A+++ |
40 | 3 | 53.49 ± 0.68 | 3 | 52.70 ± 0.55 | ||||||||
60 | 3 | 54.29 ± 0.70 | 3 | 52.70 ± 0.55 | ||||||||
80 | 3 | 54.38 ± 0.63 | 3 | 52.70 ± 0.55 | ||||||||
100 | 3 | 57.59 ± 1.02 | 3 | 52.70 ± 0.55 | ||||||||
Outcomes were described as OTM (μm) | ||||||||||||
Shi Y. 2010 [38] | China | Human fetal liver L-02 cells, exposed for 24 h | Anatase/Rutile | 30–50 | NA | 0.01 | 9 | 0.91 ± 0.75 | 9 | 0.79 ± 0.74 | high | C |
0.1 | 9 | 1.28 ± 0.96 | 9 | 0.79 ± 0.74 | ||||||||
1 | 9 | 1.30 ± 1.01 | 9 | 0.79 ± 0.74 | ||||||||
Du H. 2012 [39] | China | Human fetal liver L-02 cells, exposed for 24 h | NA | 25–50 | >99.5 | 0.001 | 3 | 0.67 ± 0.09 | 3 | 0.65 ± 0.06 | median | C |
0.01 | 3 | 0.68 ± 0.10 | 3 | 0.65 ± 0.06 | ||||||||
0.1 | 3 | 0.71 ± 0.08 | 3 | 0.65 ± 0.06 | ||||||||
1 | 3 | 0.73 ± 0.09 | 3 | 0.65 ± 0.06 | ||||||||
10 | 3 | 0.76 ± 0.09 | 3 | 0.65 ± 0.06 | ||||||||
Shukla R. K. 2011 [29] | India | Human epidermal cell line A431, exposed for 6 h | Anatase | 50 | 99.7 | 0.008 | 3 | 1.27 ± 0.05 | 3 | 1.20 ± 0.01 | high | B |
0.08 | 3 | 1.30 ± 0.03 | 3 | 1.20 ± 0.01 | ||||||||
0.8 | 3 | 1.43 ± 0.09 | 3 | 1.20 ± 0.01 | ||||||||
8 | 3 | 1.79 ± 0.08 | 3 | 1.20 ± 0.01 | ||||||||
80 | 3 | 1.91 ± 0.04 | 3 | 1.20 ± 0.01 | ||||||||
Hong L. 2011 [30] | China | Human lung adenocarcinoma cells, exposed for 6 h | NA | 5–10 | >99.9 | 25 | 25 | 12.08 ± 8.45 | 25 | 4.27 ± 2.76 | medium | A+++ |
50 | 25 | 12.43 ± 10.79 | 25 | 4.27 ± 2.76 | ||||||||
100 | 25 | 12.48 ± 2.71 | 25 | 4.27 ± 2.76 | ||||||||
200 | 25 | 8.46 ± 4.73 | 25 | 4.27 ± 2.76 | ||||||||
Shukla R. K. 2013 [31] | India | HepG2 human hepatocellular hepatoma cells, exposed for 6 h | Anatase | 30–70 | 99.7 | 1 | 3 | 1.13 ± 0,06 | 3 | 0.94 ± 0.06 | high | B |
10 | 3 | 1.20 ± 0.05 | 3 | 0.94 ± 0.06 | ||||||||
20 | 3 | 1.40 ± 0.02 | 3 | 0.94 ± 0.06 | ||||||||
40 | 3 | 1.55 ± 0.07 | 3 | 0.94 ± 0.06 | ||||||||
80 | 3 | 1.76 ± 0.09 | 3 | 0.94 ± 0.06 | ||||||||
Chen Z. 2014 [14] | China | V79 cells, exposed for 6 h, 24 h | Anatase | 75 ± 15 | 99.90 | 5 | 3 | 5.857 ± 6.198(6 h) 3.113 ± 4.285(24 h) |
3 | 4.698 ± 3.375(6 h) 2.576 ± 3.928(24 h) |
high | A+++ |
20 | 3 | 5.086 ± 4.700(6 h) 4.174 ± 7.453(24 h) |
3 | 4.698 ± 3.375(6 h) 2.576 ± 3.928(24 h) |
||||||||
100 | 3 | 4.999 ± 4.594(6 h) 3.870 ± 4.116(24 h) |
3 | 4.698 ± 3.375(6 h) 2.576 ± 3.928(24 h) |
||||||||
Ryu A. R. 2016 [40] | Korea | Peripheral blood lymphocytes of rats, exposed for 30 min | NA | NA | NA | 60 | 6 | 23.08 ± 0.52 | 6 | 8.79 ± 2.18 | low | B |
80 | 6 | 25.66 ± 6.11 | 6 | 8.79 ± 2.18 | ||||||||
Osman I. F. 2018 [36] | UK | Lymphocytes from patients with respiratory diseases, exposed for 72 h | Anatase | 40–70 | 99.7 | 10 | 40 | 4.3 ± 1.6 | 40 | 3..7 ± 1.5 | high | B |
30 | 40 | 5.0 ± 2.0 | 40 | 3..7 ± 1.5 | ||||||||
50 | 40 | 6.2 ± 2.2 | 40 | 3..7 ± 1.5 | ||||||||
Osman I. F. 2018 [36] | UK | Lymphocytes from healthy people, exposed for 72 h | Anatase | 40–70 | 99.7 | 10 | 12 | 2.3 ± 1.0 | 12 | 1.8 ± 0.7 | high | B |
30 | 12 | 2.7 ± 1.0 | 12 | 1.8 ± 0.7 | ||||||||
50 | 12 | 3.2 ± 1.2 | 12 | 1.8 ± 0.7 | ||||||||
Ünal F. 2021 [37] | Turkey | Human lymphocytes, exposed for 30 min | NA | <100 | NA | 20 | 3 | 1.01 ± 0.11 | 3 | 1.03 ± 0.09 | medium | A+++ |
40 | 3 | 1.59 ± 0.29 | 3 | 1.03 ± 0.09 | ||||||||
60 | 3 | 1.73 ± 0.36 | 3 | 1.03 ± 0.09 | ||||||||
80 | 3 | 1.49 ± 0.25 | 3 | 1.03 ± 0.09 | ||||||||
100 | 3 | 1.90 ± 0.41 | 3 | 1.03 ± 0.09 | ||||||||
Outcomes were described as MF | ||||||||||||
Xu A. 2009 [41] | US | Primary embryonic fibroblasts of transgenic mice, incubated in medium for 24 h | Anatase | 5 | 99.7 | 0.1 | 3 | 12.52 ± 4.11 | 3 | 5.69 ± 1.87 | medium | B |
Chen Z. 2014 [14] | China | V79 cells, exposed for 24 h | Anatase | 75 ± 15 | 99.9 | 100 | 3 | 22.7 ± 3.0 | 3 | 8.7 ± 1.2 | high | A+++ |
Jain A. K. 2017 [42] | India | Chinese hamster lung fibroblasts (V-79), exposed for 6 h | Anatase | 12–25 | 99.7 | 100 | 3 | 23.0 ± 2.6 | 3 | 7.7 ± 2.1 | medium | A++ |
Outcomes were described as MN frequency (BiMN) | ||||||||||||
Shi Y. 2010 [38] | China | Human fetal liver L-02 cells, exposed for 24 h | Anatase/Rutile | 30–50 | NA | 0.01 | 9 | 0.91 ± 0.75 | 9 | 0.79 ± 0.74 | high | C |
0.1 | 9 | 1.28 ± 0.96 | 9 | 0.79 ± 0.74 | ||||||||
1 | 9 | 1.30 ± 1.01 | 9 | 0.79 ± 0.74 | ||||||||
Kang S. J. 2008 [43] | South Korea | Peripheral blood lymphocytes, exposed for 20 h | Anatase/Rutile | 25 | NA | 20 | 3 | 15.00 ± 1.00 | 3 | 9.33 ± 1.52 | median | C |
50 | 3 | 18.33 ± 2.08 | 3 | 9.33 ± 1.52 | ||||||||
100 | 3 | 23.67 ± 0.58 | 3 | 9.33 ± 1.52 | ||||||||
Reis É.deM 2016 [44] | Brazil | V79 cells, exposed for 3 h | Anatase | 3.4 | 99.7 | 30 | 3 | 6.67 ± 1.15 | 3 | 7.00 ± 1.00 | high | C |
60 | 3 | 12.00 ± 1.00 | 3 | 7.00 ± 1.00 | ||||||||
120 | 3 | 14.67 ± 2.06 | 3 | 7.00 ± 1.00 | ||||||||
Reis É.deM 2016 [44] | Brazil | V79 cells, exposed for 3 h | Anatase | 6.2 | 99.7 | 30 | 3 | 11.33 ± 2.31 | 3 | 7.00 ± 1.00 | high | C |
60 | 3 | 8.33 ± 1.15 | 3 | 7.00 ± 1.00 | ||||||||
120 | 3 | 10.00 ± 2.00 | 3 | 7.00 ± 1.00 | ||||||||
Reis É.deM 2016 [44] | Brazil | V79 cells, exposed for 3 h | Anatase | 78 | 99.7 | 30 | 3 | 5.33 ± 1.53 | 3 | 7.00 ± 1.00 | high | C |
60 | 3 | 7.67 ± 1.15 | 3 | 7.00 ± 1.00 | ||||||||
120 | 3 | 12.33 ± 2.52 | 3 | 7.00 ± 1.00 | ||||||||
Shukla R. K. 2011 [29] | India | Human epidermal cell line A431, exposed for 6 h | Anatase | 50 | 99.7 | 0.008 | 3 | 11.67 ± 1.20 | 3 | 9.33 ± 1.00 | high | B |
0.08 | 3 | 12.67 ± 0.88 | 3 | 9.33 ± 1.00 | ||||||||
0.8 | 3 | 14.67 ± 1.20 | 3 | 9.33 ± 1.00 | ||||||||
8 | 3 | 15.67 ± 0.88 | 3 | 9.33 ± 1.00 | ||||||||
80 | 3 | 16.00 ± 0.58 | 3 | 9.33 ± 1.00 | ||||||||
Srivastava R. K. 2013 [45] | India | Human lung cancer cell line (A549), exposed for 24 h | Anatase | <25 | NA | 10 | 3 | 12.66 ± 0.33 | 3 | 5.33 ± 0.33 | medium | B |
50 | 3 | 17.33 ± 0.33 | 3 | 5.33 ± 0.33 | ||||||||
Shukla R. K. 2013 [31] | India | HepG2 human hepatocellular carcinoma cells, exposed for 6 h | Anatase | 30–70 | 99.7 | 1 | 3 | 8.00 ± 1.15 | 3 | 7.00 ± 0.58 | high | B |
10 | 3 | 11.00 ± 1.53 | 3 | 7.00 ± 0.58 | ||||||||
20 | 3 | 15.00 ± 0.58 | 3 | 7.00 ± 0.58 | ||||||||
40 | 3 | 12.33 ± 0.33 | 3 | 7.00 ± 0.58 | ||||||||
80 | 3 | 10.67 ± 0.88 | 3 | 7.00 ± 0.58 | ||||||||
Kansara K. 2015 [34] | India | Human lung cancer cell line (A549), exposed for 6 h | Anatase | 4–8 | 99.7 | 25 | 3 | 7.33 ± 1.20 | 3 | 6.00 ± 2.80 | medium | B |
50 | 3 | 9.66 ± 2.84 | 3 | 6.00 ± 2.80 | ||||||||
75 | 3 | 12.33 ± 2.96 | 3 | 6.00 ± 2.80 | ||||||||
100 | 3 | 14.66 ± 2.33 | 3 | 6.00 ± 2.80 | ||||||||
Andreoli C. 2018 [35] | Italy | Peripheral blood monocytes, exposed for 24 h | Anatase | 20–60 | >99.5 | 50 | 2 | 9.0 ± 1.41 | 2 | 8.5 ± 0.71 | medium | A |
100 | 2 | 10.0 ± 4.24 | 2 | 8.5 ± 0.71 | ||||||||
Andreoli C. 2018 [35] | Italy | Peripheral blood monocytes, exposed for 24 h | Rutile | 30 × 100 | >99.5 | 50 | 2 | 9.0 ± 2.83 | 2 | 7.5 ± 3.54 | medium | A |
100 | 2 | 7.0 ± 2.83 | 2 | 7.5 ± 3.54 | ||||||||
200 | 2 | 8.0 ± 1.41 | 2 | 7.5 ± 3.54 | ||||||||
Andreoli C. 2018 [35] | Italy | Peripheral blood monocytes, exposed for 24 h | Anatase/Rutile | 45–262 | >99.5 | 50 | 2 | 9.5 ± 0.71 | 2 | 9.5 ± 0.71 | medium | A |
100 | 2 | 8.0 ± 4.24 | 2 | 9.5 ± 0.71 | ||||||||
200 | 2 | 5.5 ± 2.12 | 2 | 9.5 ± 0.71 | ||||||||
Osman I. F. 2018 [36] | UK | Lymphocytes from patients with respiratory diseases, exposed for 72 h | Anatase | 40–70 | 99.7 | 5 | 40 | 8.29 ± 1.55 | 40 | 8.54 ± 1.40 | high | B |
10 | 40 | 11.03 ± 1.70 | 40 | 8.54 ± 1.40 | ||||||||
Osman I. F. 2018 [36] | UK | Lymphocytes from healthy people, exposed for 72 h | Anatase | 40–70 | 99.7 | 5 | 12 | 4.47 ± 2.39 | 12 | 1.87 ± 1.63 | high | B |
10 | 12 | 7.21 ± 1.69 | 12 | 1.87 ± 1.63 | ||||||||
Ünal F. 2021 [37] | Turkey | Human lymphocytes, exposed for 48 h | NA | <100 | NA | 20 | 3 | 0.30 ± 0.099 | 3 | 0.13 ± 0.066 | medium | A+++ |
40 | 3 | 0.30 ± 0.099 | 3 | 0.13 ± 0.066 | ||||||||
60 | 3 | 0.30 ± 0.099 | 3 | 0.13 ± 0.066 | ||||||||
80 | 3 | 0.17 ± 0.075 | 3 | 0.13 ± 0.066 | ||||||||
100 | 3 | 0.13 ± 0.066 | 3 | 0.13 ± 0.066 | ||||||||
Outcomes were described as CA frequency | ||||||||||||
Catalán J. 2011 [46] | Finland | Human lymphocytes, exposed for 24 h, 48 h and 72 h | Anatase | <25 | 99.7 | 6.25 | 2 | 1.25 ± 1.26(24 h) 0.50 ± 0.58(48 h) 0.25 ± 0.50(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
high | A++ |
12.5 | 2 | 0.50 ± 0.58(24 h) 0.50 ± 0.58(48 h) 1.25 ± 0.96(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
||||||||
25 | 2 | 0.00 ± 0.00(24 h) 0.25 ± 0.50(48 h) 0.25 ± 0.50(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
||||||||
50 | 2 | 0.50 ± 0.58(24 h) 0.25 ± 0.50(48 h) 0.50 ± 1.00(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
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100 | 2 | 0.00 ± 0.00(24 h) 1.00 ± 0.82(48 h) 0.75 ± 0.96(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
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150 | 2 | 0.25 ± 0.50(24 h) 1.25 ± 0.50(48 h) 0.50 ± 0.58(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
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300 | 2 | 1.00 ± 1.15(24 h) 1.00 ± 0.82(48 h) 0.50 ± 0.58(72 h) |
2 | 0.75 ± 0.96(24 h) 0.00 ± 0.00(48 h) 0.50 ± 1.00(72 h) |
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Ünal F. 2021 [37] | Turkey | Human lymphocytes, exposed for 24 h, 48 h | NA | <100 | NA | 20 | 3 | 6.00 ± 1.37(24 h) 5.33 ± 1.30(48 h) |
3 | 1.33 ± 0.66(24 h) 1.33 ± 0.66(48 h) |
medium | A+++ |
40 | 3 | 6.67 ± 1.44(24 h) 3.00 ± 0.98(48 h) |
3 | 1.33 ± 0.66(24 h) 1.33 ± 0.66(48 h) |
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60 | 3 | 4.33 ± 1.17(24 h) 3.33 ± 1.03(48 h) |
3 | 1.33 ± 0.66(24 h) 1.33 ± 0.66(48 h) |
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80 | 3 | 5.00 ± 1.26(24 h) 3.33 ± 1.03(48 h) |
3 | 1.33 ± 0.66(24 h) 1.33 ± 0.66(48 h) |
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100 | 3 | 6.00 ± 1.37(24 h) 4.00 ± 1.13(48 h) |
3 | 1.33 ± 0.66(24 h) 1.33 ± 0.66(48 h) |
1 NA: not applicable; n: sample size; SD: standard deviation; T DNA%: the percentage of DNA in tail; TL: tail length; OTM: olive tail moment; MF: mutation frequency; BiMN: no. of micronucleus/1000 binucleated cells; CA frequency: percentage of cells exhibiting chromosomal aberrations.