Undetactable levels of genotoxicity of SiO₂ nanoparticles in in vitro and in vivo tests

Figures & data

Table 1 Numbers of revertant colonies induced by SiO₂^EN20(−) and SiO₂^EN100(−) in Salmonella typhimurium (TA98, TA100, TA1535, TA1537) and Escherichia coli (WP2uvrA) with and without metabolic activation (S9)

Colonies per plate (mean ± standard deviation)
Tester strain	Dose (μg per plate)	SiO2^EN20(−)		SiO2^EN100(−)
		Without S9 mix	With S9 mix	Without S9 mix	With S9 mix
TA98	0	17±6	28±4	16±2	19±6
	313	16±4	25±6	14±2	27±3
	625	15±5	22±7	11±2	21±5
	1,250	17±6	22±5	10±4	21±1
	2,500	16±3	28±7	13±5	23±2
	5,000	11±1	18±2	16±5	20±4
	Positive control	434±20*,a	201±26*,b	361±15*,a	199±16*,b
TA100	0	84±7	101±5	75±8	100±12
	313	85±9	117±9	80±7	99±6
	625	99±7	120±7	87±8	100±7
	1,250	100±7	128±9	69±6	104±10
	2,500	92±5	120±11	66±5	103±17
	5,000	100±8	118±12	69±5	95±17
	Positive control	419±46*,a	390±8*,b	361±30*,a	265±21*,b
TA1535	0	12±4	10±1	10±1	9±1
	313	10±2	10±2	13±5	10±5
	625	13±5	12±2	10±2	8±2
	1,250	12±2	12 ±51	9±2	9±3
	2,500	15±1	12±2	8±3	8±3
	5,000	18±5	14±1	9±4	10±3
	Positive control	236±26*,c	216±14*,b	323±7*,c	195±4*,b
TA1537	0	6±2	12±2	7±1	17±3
	313	6±1	13±2	7±3	16±5
	625	4±1	15±1	7±1	14±4
	1,250	7±0	10±1	8±3	13±4
	2,500	6±2	8±2	8±2	15±4
	5,000	6±0	9±1	7±2	13±3
	Positive control	761±30*,d	184±13*,b	753±22*,d	200±13*,b
WP2uvrA	0	32±4	33±4	41±2	39±4
	313	35±6	44±6	39±4	39±7
	625	39±6	46±9	39±5	41±6
	1,250	39±5	43±8	39±6	32±4
	2,500	37±9	46±5	42±4	36±10
	5,000	39±7	46±5	38±2	36±3
	Positive control	424±17*,a	265±8*,b	238±22*,a	242±17*,b

Notes:

* P<0.01.

a 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide;

b 2-aminoanthracene;

c sodium azide;

d 9-aminoacridine.

Abbreviations: SiO₂^EN20(−), SiO₂ colloids 20 nm; SiO₂^EN100(−), SiO₂ colloids 100 nm.

Table 2 Chromosome analysis of SiO₂^EN20(−) and SiO₂^EN100(−) in Chinese hamster lung fibroblast cells with and without metabolic activation (S9)

Observed cell	Concentration (μg/mL)	SiO2^EN20(−)		SiO2^EN100(−)
		% numerical aberration	% structural aberration (exclusive to gap)	% numerical aberration	% structural aberration (exclusive to gap)
(A) 6 hours without S9 (−S9)
200	0	0.0	1.5	0.0	1.5
	175	0.5	1.0	0.0	0.0
	350	0.5	1.0	1.0	1.0
	700	0.0	0.5	0.0	1.0
	1,400	0.0	0.5	0.0	0.5
	Positive controla	0.0	54.0*	0.5	44.5*
(B) 6 hours with S9 (+S9)
200	0	0.0	1.0	0.5	0.5
	175	0.5	0.5	0.5	1.5
	350	0.0	1.5	0.5	1.0
	700	0.0	0.5	0.0	1.0
	1,400	0.0	1.0	1.0	1.5
	Positive controlb	1.5	54.0*	0.5	51.5*

Notes:

a Mitomycin C;

b cyclophosphamide.

* P<0.01.

Abbreviations: SiO₂^EN20(−), SiO₂ colloids 20 nm; SiO₂^EN100(−), SiO₂ colloids 100 nm.

Figure 1 DNA damage determined by in vivo comet assay in liver and stomach tissues from rats treated with (A) SiO₂^EN20(−) and (B) SiO₂^EN100(−).

Note: The yellow and black images indicate comet images in each group.

Abbreviations: NC, negative control; PC, positive control; EMS, ethyl methansulfonate; SiO₂^EN20(−), SiO₂ colloids 20 nm; SiO₂^EN100(−), SiO₂ colloids 100 nm.

Table 3 Frequencies of MNPCE per 2,000 PCE in the bone marrow of ICR mice exposed to SiO₂^EN20(−) and SiO₂^EN100(−)

Dose (mg/kg body weight)	SiO2^EN20(−)		SiO2^EN100(−)
	MNPCE/2,000 PCE (mean ± SD, %)	PCE/(PCE + NCE) (mean ± SD, %)	MNPCE/2,000 PCE (mean ± SD, %)	PCE/(PCE + NCE) (mean ± SD, %)
0	0.10±0.04	53.64±2.27	0.09±0.05	53.93±2.79
500	0.13±0.07	56.11±2.46	0.06±0.02	52.98±2.76
1,000	0.10±0.06	55.11±2.81	0.14±0.09	55.19±1.55
2,000	0.10±0.05	56.02±1.32	0.09±0.04	56.24±0.89
Positive controla	4.33±0.37*	44.57±2.06*	4.82±0.92*	43.20±1.28*

a Notes: Cyclophosphamide.

* P<0.01.

Abbreviations: SD, standard deviation; PCE, polychromatic erythrocytes; NCE, normochromatic erythrocytes; MNPCE, micronucleated polychromatic erythrocytes; SiO₂^EN20(−), SiO₂ colloids 20 nm; SiO₂^EN100(−), SiO₂ colloids 100 nm.