Table 1.
Basic characteristics and quality evaluation of the included studies on in vivo genotoxicity of TiO2 NPs 1.
| Included Studies | Country | Test Animals and Exposure Methods | TiO2-NP Characteristics | Dose (mg/kg bw) |
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. 2014 [17] | India | Male Swiss albino mice (continuous gavage for 14 d) | Anatase | 20–50 | 99.7 | 10 | 5 | 17.72 ± 0.72 | 5 | 14.29 ± 0.67 | high | A+++ |
| 50 | 5 | 18.98 ± 1.21 | 5 | 14.29 ± 0.67 | ||||||||
| 100 | 5 | 20.28 ± 1.11 | 5 | 14.29 ± 0.67 | ||||||||
| Martins A. D. C., Jr. 2017 [18] | Brazil | Male Wistar rats (continuous gavage for 45 d) | NA | 41.99 ± 1.63 | NA | 0.5 | 6 | 4.64 ± 0.82 | 6 | 3.6 ± 0.35 | medium | B+++ |
| Fadda L. M. 2018 [19] | Saudi Arabia | Male Wistar Albino rats (continuous gavage for 21 d) | Anatase | 60 ± 10 | NA | 1000 | 10 | 4.32 ± 0.24 | 10 | 2.26 ± 0.31 | medium | B+++ |
| Chakrabarti S. 2019 [20] | India | Female/male Swiss-Albino mice (oral for 90 d) | NA | 58.25 ± 8.11 | NA | 200 | 10 | 0.07 ± 0.012 (liver) 0.085 ± 0.009 (kidney) |
10 | 0.068 ± 0.007 (liver) 0.084 ± 0.004 (kidney) |
high | A+++ |
| 500 | 10 | 0.236 ± 0.066 (liver) 0.27 ± 0.075 (kidney) |
10 | 0.068 ± 0.007 (liver) 0.084 ± 0.004 (kidney) |
||||||||
| Sallam M. F. 2022 [21] | Egypt | Male SD rats (continuous gavage for 21 d) | NA | 50 ± 2.4 | NA | 50 | 10 | 19.25 ± 0.86 | 10 | 9.05 ± 0.25 | medium | B++ |
| Sallam M. F. 2022 [22] | Egypt | Male SD rats (continuous gavage for 21 d) | NA | 28 | NA | 50 | 10 | 18.74 ± 1.77 | 10 | 9.77 ± 1.24 | medium | B++ |
| Outcomes were described as TL (μm) | ||||||||||||
| Hassanein K. M. 2016 [23] | Egypt | Adult male SD rats (continuous gavage for 90 d) | NA | 21 | NA | 150 | 10 | 20.39 ± 1.6 | 10 | 10.57 ± 1.3 | medium | A+++ |
| Fadda L. M. 2018 [19] | Saudi Arabia | Male Wistar Albino rats (continuous gavage for 21 d) | NA | 60 ± 10 | NA | 1000 | 10 | 4.27 ± 0.10 | 10 | 1.14 ± 0.13 | medium | B+++ |
| Chakrabarti S. 2019 [20] | India | Female/male Swiss-Albino mice (oral for 90 d) | NA | 58.25 ± 8.11 | NA | 200 | 10 | 0.579 ± 0.041 (liver) 0.655 ± 0.009 (kidney) |
10 | 0.575 ± 0.028 (liver) 0.651 ± 0.007 (kidney) |
high | A+++ |
| 500 | 10 | 2.213 ± 0.059 (liver) 1.858 ± 0.041 (kidney) |
10 | 0.575 ± 0.028 (liver) 0.651 ± 0.007 (kidney) |
||||||||
| Outcomes were described as OTM (μm) | ||||||||||||
| Shukla R. K. 2014 [17] | India | Male Swiss albino mice (continuous gavage for 14 d) | Anatase | 20–50 | 99.7 | 10 | 5 | 2.71 ± 0.25 | 5 | 1.93 ± 0.14 | high | A+++ |
| 50 | 5 | 2.98 ± 0.22 | 5 | 1.93 ± 0.14 | ||||||||
| 100 | 5 | 3.76 ± 0.23 | 5 | 1.93 ± 0.14 | ||||||||
| Mohamed H. R. 2015 [24] | Egypt | Male Swiss Webster mice (continuous gavage for 5 d) | Anatase/Rutile | 46.23 ± 3.45 | 99.5 | 5 | 5 | 3.01 ± 0.36 | 5 | 1.86 ± 0.26 | medium | B+++ |
| 50 | 5 | 3.43 ± 0.71 | 5 | 1.86 ± 0.26 | ||||||||
| 500 | 5 | 5.78 ± 2.02 | 5 | 1.86 ± 0.26 | ||||||||
| Shi Z. 2015 [25] | China | Female/male wild-type ICR mice, Nrf2(-/-) ICR mice (continuous gavage for 7 d) | Anatase | 10–25 | 99.7 | 500 | 8 | 1.43 ± 0.15 (liver) 2.06 ± 0.28 (kidney) |
8 | 0.84 ± 0.30 (liver) 0.61 ± 0.24 (kidney) |
high | A+++ |
| 1000 | 8 | 3.29 ± 0.21 (liver) 4.33 ± 0.36 (kidney) |
8 | 0.84 ± 0.30 (liver) 0.61 ± 0.24 (kidney) |
||||||||
| 2000 | 8 | 8.59 ± 2.67 (liver) 8.07 ± 2.91 (kidney) |
8 | 0.84 ± 0.30 (liver) 0.61 ± 0.24 (kidney) |
||||||||
| Chakrabarti S. 2019 [20] | India | Female/male Swiss-Albino mice (oral for 90 d) | NA | 58.25 ± 8.11 | NA | 200 | 10 | 0.546 ± 0.041 (liver) 0.554 ± 0.01 (kidney) |
10 | 0.523 ± 0.025 (liver) 0.549 ± 0.007 (kidney) |
high | A+++ |
| 500 | 10 | 0.835 ± 0.074 (liver) 0.758 ± 0.026 (kidney) |
10 | 0.523 ± 0.025 (liver) 0.549 ± 0.007 (kidney) |
||||||||
| Sallam M. F. 2022 [21] | Egypt | Male SD rats (continuous gavage for 21 d) | NA | 50 ± 2.4 | NA | 50 | 10 | 2.74 ± 0.17 | 10 | 1.08 ± 0.04 | medium | B++ |
| Sallam M. F. 2022 [22] | Egypt | Male SD rats (continuous gavage for 21 d) | NA | 28 | NA | 50 | 10 | 3.57 ± 0.14 | 10 | 1.12 ± 0.02 | medium | B++ |
| Outcomes were described as MN frequency (MN/1000 PCEs) | ||||||||||||
| Shukla R. K. 2014 [17] | India | Male Swiss albino mice (continuous gavage for 14 d) | Anatase | 20–50 | 99.7 | 10 | 5 | 1.50 ± 0.51 | 5 | 1.20 ± 0.20 | high | A+++ |
| 50 | 5 | 2.25 ± 0.49 | 5 | 1.20 ± 0.20 | ||||||||
| 100 | 5 | 3.0 ± 0.68 | 5 | 1.20 ± 0.20 | ||||||||
| Chakrabarti S. 2019 [20] | India | Female/male Swiss-Albino mice (oral for 90 d) | NA | 58.25 ± 8.11 | NA | 200 | 10 | 5.83 ± 0.75 | 10 | 0.16 ± 0.40 | high | A+++ |
| 500 | 10 | 7.16 ± 0.75 | 10 | 0.16 ± 0.40 | ||||||||
| Outcomes were described as CA frequency | ||||||||||||
| Ali S. A. 2019 [26] | Egypt | Male Swiss albino mice (continuous oral for 5 d) | NA | 21 | NA | 50 | 15 | 13.30 ± 0.98 | 15 | 4.72 ± 0.24 | medium | A+++ |
| 250 | 15 | 15.80 ± 0.34 | 15 | 4.72 ± 0.24 | ||||||||
| 500 | 15 | 31.70 ± 0.67 | 15 | 4.72 ± 0.24 | ||||||||
| Ali S. A. 2019 [26] | Egypt | Male Swiss albino mice (continuous oral for 5 d) | NA | 80 | NA | 50 | 15 | 12.00 ± 0.66 | 15 | 4.72 ± 0.24 | medium | A+++ |
| 250 | 15 | 15.00 ± 0.69 | 15 | 4.72 ± 0.24 | ||||||||
| 500 | 15 | 24.00 ± 1.67 | 15 | 4.72 ± 0.24 | ||||||||
| Manivannan J. 2019 [27] | India | Male Swiss albino mice (continuous gavage for 28 d) | Rutile | 25.074 ± 3.593 | NA | 0.2 | 5 | 0.05 ± 0.04 | 5 | 0.01 ± 0.01 | high | B+++ |
| 0.4 | 5 | 0.14 ± 0.04 | 5 | 0.01 ± 0.01 | ||||||||
| 0.8 | 5 | 0.19 ± 0.03 | 5 | 0.01 ± 0.01 | ||||||||
| Chakrabarti S. 2019 [20] | India | Female/male Swiss-Albino mice (oral for 90 d) | NA | 58.25 ± 8.11 | NA | 200 | 10 | 0.83 ± 0.23 | 10 | 0.76 ± 0.29 | high | A+++ |
| 500 | 10 | 1.9 ± 0.20 | 10 | 0.76 ± 0.29 | ||||||||
| Salman A. S. 2021 [28] | Germany | Male Balb/c mice (continuous gavage for 21 d) | NA | 28.9 | NA | 25 | 6 | 13.2 ± 0.35 | 6 | 1.6 ± 0.2 | high | A+++ |
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; MN/1000 PCEs: no. of micronucleus/1000 polychromatic erythrocytes; CA frequency: percentage of cells exhibiting chromosomal aberrations.