In vivo micronucleus studies with 6 titanium dioxide materials (3 pigment-grade &amp; 3 nanoscale) in orally-exposed rats

Donner, Erica; Myhre, A.; Brown, Scott C.; Boatman, Rodney J.

doi:10.1016/j.yrtph.2015.11.003

Cited by 22 publications

(19 citation statements)

References 21 publications

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“…Donner et al. () evaluated three pigment grades (size range 153–213 nm) and three nanoscale (size range 43–47 nm) TiO 2 particle samples (both anatase and/or rutile) in an in vivo micronucleus test performed in compliance with OECD Guideline No. 474 (2014) and Good laboratory Practice (GLP).…”

Section: Biological and Toxicological Datamentioning

confidence: 99%

“…In another oral in vivo study, the intragastric administration of TiO 2 nanoparticles for 30 days to rats resulted in an increase in H2AX phosphorylated loci in bone marrow (an indication of double‐strand break DNA repair), with no concurrent increase of chromosome breaks (micronuclei) (Chen et al., ). Negative results were also obtained in a micronucleus assay on rat blood cells after administration by gavage of acute doses of both nano‐ and microsized TiO 2 particles (Donner et al., ).…”

Section: Biological and Toxicological Datamentioning

confidence: 99%

“…The Panel also noted that the intraperitoneal route of administration applied in this study is not recommended by OECD guidelines, as nonphysiological, and that study results obtained with this route have no relevance for oral risk assessment. Donner et al (2016) evaluated three pigment grades (size range 153-213 nm) and three nanoscale (size range 43-47 nm) TiO 2 particle samples (both anatase and/or rutile) in an in vivo micronucleus test performed in compliance with OECD Guideline No. 474 (2014) and Good laboratory Practice (GLP).…”

Section: In Vivomentioning

confidence: 99%

“…Negative results were also obtained in a micronucleus assay on rat blood cells after administration by gavage of acute doses of both nano-and microsized TiO 2 particles (Donner et al, 2016).…”

Section: Nanosized Tio 2 Particlesin Vivomentioning

confidence: 99%

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Re-evaluation of titanium dioxide (E 171) as a food additive

2016

EFSA Journal

114

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The present Opinion deals with the re-evaluation of the safety of titanium dioxide (TiO 2 , E 171) when used as a food additive. From the available data on absorption, distribution and excretion, the EFSA Panel on Food Additives and Nutrient Sources added to Food concluded that the absorption of orally administered TiO 2 is extremely low and the low bioavailability of TiO 2 appears to be independent of particle size. The Panel concluded that the use of TiO 2 as a food additive does not raise a genotoxic concern. From a carcinogenicity study with TiO 2 in mice and in rats, the Panel chose the lowest no observed adverse effects levels (NOAEL) which was 2,250 mg TiO 2 /kg body weight (bw) per day for males from the rat study, the highest dose tested in this species and sex. The Panel noted that possible adverse effects in the reproductive system were identified in some studies conducted with material which was either non-food-grade or inadequately characterised nanomaterial (i.e. not E 171). There were no such indications in the available, albeit limited, database on reproductive endpoints for the food additive (E 171). The Panel was unable to reach a definitive conclusion on this endpoint due to the lack of an extended 90-day study or a multigeneration or extended-one generation reproduction toxicity study with the food additive (E 171). Therefore, the Panel did not establish an acceptable daily intake (ADI). The Panel considered that, on the database currently available and the considerations on the absorption of TiO 2 , the margins of safety (MoS) calculated from the NOAEL of 2,250 mg TiO 2 /kg bw per day identified in the toxicological data available and exposure data obtained from the reported use/analytical levels of TiO 2 (E 171) would not be of concern. The Panel concluded that once definitive and reliable data on the reproductive toxicity of E 171 were available, the full dataset would enable the Panel to establish a health-based guidance value (ADI).

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Section: Biological and Toxicological Datamentioning

confidence: 99%

Section: Biological and Toxicological Datamentioning

confidence: 99%

Section: In Vivomentioning

confidence: 99%

Section: Nanosized Tio 2 Particlesin Vivomentioning

confidence: 99%

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Re-evaluation of titanium dioxide (E 171) as a food additive

2016

EFSA Journal

114

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“…Genotoxicity is one of the key factors to assess the carcinogenic risk to humans. Several studies in mice and rats have reported conflicting results of various genotoxic endpoint analyses [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Recently, we reported that TiO 2 NPs have no genotoxic effects in the liver and erythrocytes when intravenously injected into gpt delta mice [17], but there are still reports about their positive effect [18,19].…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice

et al. 2020

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Backgound: A variety of in vivo and in vitro studies to assess the genotoxicity of titanium dioxide nanoparticles (TiO 2 NPs) have been reported, but the results are inconsistent. Recently, we reported that TiO 2 NPs exhibit no genotoxic effects in the liver and erythrocytes during a relatively brief period following intravenous injection into mice. However, there is no information about long-term genotoxicity due to TiO 2 NP accumulation in tissues. In this study, we investigated the long-term mutagenic effects of TiO 2 NPs and the localization of residual TiO 2 NPs in mouse liver after multiple intravenous injections.Results: Male gpt delta C57BL/6 J mice were administered with various doses of TiO 2 NPs weekly for 4 consecutive weeks. The long-term mutagenic effects on the liver were analyzed using gpt and Spi − mutation assays 90 days after the final injection. We also quantified the amount of titanium in the liver using inductively coupled plasma mass spectrometry and observed the localization of TiO 2 NPs in the liver using transmission electron microscopy. Although TiO 2 NPs were found in the liver cells, the gpt and Spi − mutation frequencies in the liver were not significantly increased by the TiO 2 NP administration. Conclusions:These results clearly show that TiO 2 NPs have no mutagenic effects on the liver, even though the particles remain in the liver long-term.

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Hepatotoxicity of titanium dioxide nanoparticles

Khan,

Kim,

Bromhead

et al. 2024

J of Applied Toxicology

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The food additive E171 (titanium dioxide, TiO2), is widely used in foods, pharmaceuticals and cosmetics. It is a fine white powder, with at least one third of its particles sized in the nanoparticulate (˂100 nm range, TiO2 NPs). The use of E171 is controversial as its relevant risk assessment has never been satisfactorily accomplished. In vitro and in vivo studies have shown dose‐dependent toxicity in various organs including the liver. TiO2 NPs have been shown to induce inflammation, cell death and structural and functional changes within the liver. The toxicity of TiO2 NPs in experimental models varies between organs and according to their physiochemical characteristics and parameters such as dosage and route of administration. Among these factors, ingestion is the most significant exposure route, and the liver is a key target organ. The aim of this review is to highlight the reported adverse effects of orally administered TiO2 NPs on the liver and to discuss the controversial state of its toxicity.

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In vivo micronucleus studies with 6 titanium dioxide materials (3 pigment-grade & 3 nanoscale) in orally-exposed rats

Cited by 22 publications

References 21 publications

Re-evaluation of titanium dioxide (E 171) as a food additive

Re-evaluation of titanium dioxide (E 171) as a food additive

Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice

Hepatotoxicity of titanium dioxide nanoparticles

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