Table 1 Characteristics of included studies, reporting use of micronucleus or comet assay, ordered by administration and study design
Identifier | Nanoparticles size & source/manufacture | Animal model | Target organ | Admin. | Study design | Dose administered | Time to sacrifice | Method | Genotoxic effect reported | Summary of results | Quality estimate |
|---|---|---|---|---|---|---|---|---|---|---|---|
Al Gurabi 2015 [35] | mean 43.6 nm (reduction with aniline and CTAB) | Swiss albino mice | Peripheral blood | IP | Single dose | 26, 52 & 78 mg/kg | 24 and 72 h | Alkaline comet assay | y | Increased DNA strand breakages with all doses at 72 h post-exposure | 3 (14) no +ve control; choice of frequency & duration of exposure not explained |
Chen 2015 [18] | 8 nm (poly styrene-co-maleic anhydride-coated) | Mice | Peripheral blood | IP | Single dose | 0.25 & 1.0 mg/kg | 48 & 72 h after injection | Micronucleus assay | n | No significant difference | 3 (16) no –ve control, MN not scored in enough cells |
Ghosh 2012 [36] | 90–180 nm (Sigma-Aldrich) | Mice | Bone marrow | IP | Single dose | 10, 20, 40 & 80 mg/kg body weight | 18 h | Alkaline comet assay & microscopic examination of cells in metaphase | y | Significant increases seen in both the comet assay and chromosome aberration test at all doses. No clear dose–response relationship | 2 (19) choice of frequency & duration of exposure not explained |
Ordzhonikidze 2009 [16] | 9 nm | Mice | Spleen | IP | Single dose | 1.5 mg/kg | From 3 to 48 h | Neutral comet assay | n | A non-significant increase in DNA damage seen for both AgNP and the anionic surfactant used as a stabilizer | 3 (13) no +ve control, use of neutral comet assay |
Asare 2016 [37] | 20 nm and 200 nm (PlasmaChem) | Mice | Lung, liver and testes | IV | Single dose | 5 mg/kg | 1 or 7 d post injection | Alkaline comet assay | n | No significant effect in any tissue (20 nm) | 3 (18) no +ve control; time to sacrifice not ideal for comet assay |
Dobrzyńska 2014 [38] | 20 nm or 200 nm (PlasmaChem) | Rats | Bone marrow | IV | Single dose | 5 & 10 mg/kg bw of 20 nm size AgNPs 5 mg/kg bw of 200 nm size AgNPs | 24 h, 1 week and 4 weeks post-exposure | Alkaline comet and micronucleus assays | y | No effect seen in comet assay. Significantly increased frequency of erythrocyte micronuclei after 24 h of exposure for both doses. Enhanced frequency also seen at 1 and 4 weeks | 3 (18) no +ve control |
Gromadzka-Ostrowska 2012 [20] | 20 & 200 nm (PlasmaChem) | male Wistar rats | Testes | IV | Single dose | 5 & 10 mg/kg | 24 h, 7 and 28 d post injection | Allkaline comet assay | y | Significant increased risk of DNA damage in spermatozoa seen 24 h post-exposure for 20 nm AgNP | 3 (18) no +ve control |
Tavares 2012 [17] | 5–45 nm (citrate reduction) | Swiss mice | Peripheral blood | IV | Single dose | 10, 25 & 50 μg/kg bw | 1, 6, 12, and 24 h | Alkaline comet assay | n | Limited effects with only the lowest dose (after 24 h) producing a significant increase in DNA damage compared to the control | 3 (17) no +ve control, no of animals/group not clearly stated |
Kim 2011 [39] | 18 nm ave. (naked) | Sprague-Dswley rats | Bone marrow | Inhalation | Repeated dose | 30, 300 & 1000 mg/kg bw for 90 days | 24 h | Micronucleus assay | n | No statistically significant differences were seen | 3 (19) no +ve control |
Awasthi 2015a [40] | 5 nm | Swiss albino mice | Liver | Oral | Repeated dose | 10 & 20 mg/kg bw once a week for 5 weeks | 3 h after last dose | Alkaline comet assay | y | Significant DNA damage was seen at both doses | 2 (17) |
Awasthi 2015b [19] | 10 nm | Swiss albino mice | Liver | Oral | Repeated dose | 50 & 100 mg/kg bw on alternate days for 28 days | After exposure to the dosing regime | Alkaline comet assay | y | Dose-related increase in DNA damage seen, statistically significant at highest dose | 3 (15) no +ve control |
Kim 2008 [10] | 60 nm (Nanatech Co. Ltd) CMC | Sprague–Dawley Rats | Bone marrow | Oral | Repeated dose | 30, 300, and 1000 mg/kg/day for 28 days | 24 h after last dose | Micronucleus assay | n | Non-significant increase in evidence of DNA damage with increasing dose | 3 (19) no +ve control |
Kovvuru 2015 [28] | 5–150 nm (Sigma-Aldrich – PVP coated) | Mice | Offspring, peripheral blood, bone marrow | Oral | Repeated dose | 500 mg/kg bw daily for 5 days | 20 d for offspring, 24 h after first and last dose for blood and 24 h after last treatment for bone marrow | Micronucleus assay | y | Significant induction of micronuclei seen in blood (at 1 and 5 days) and bone marrow. Maternal ingestion of AgNP during gestation was found to induce large-scale genome rearrangements in developing embryos | 3 (19) no +ve control |
Patlolla 2015 [41] | 10 nm (Ocean Nanotech) | Sprague–Dawley rats | Bone marrow | Oral | Repeated dose | 5, 25, 50, 100, mg/kg bw, daily for five days | 24 h after last dose | Comet and micronucleus assay | y | Significant effects seen in comet and micronucleus assays for doses of 50 mg/kg bw and above | 3 (20) no +ve control |
Awasthi 2015a [40] | 5 nm | Swiss albino mice | Liver | Oral | Single dose | 50 & 100 mg/kg bw | 3 and 24 h after dose | Comet assay | y | Significant difference in all comet assay parameters (3 & 24 h) for highest dose | 2 (17) |