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

Suzuki, Tetsuya; Miura, Nobuhiko; Hojo, Rieko; Yanagiba, Yukie; Suda, Megumi; Hasegawa, Tatsuya; Miyagawa, Munéyuki; Wang, Rui-Sheng

doi:10.1186/s41021-020-0146-3

Cited by 13 publications

(8 citation statements)

References 27 publications

(57 reference statements)

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“…TiO 2 NPs (< 30 nm) were administered to male gpt Delta transgenic C57BL/6J mice at doses up to 50 mg/kg bw once a week for 4 weeks, then Pig-a mutation was analysed in erythrocytes and gpt and Spimutation in liver (Suzuki et al, 2016). In another assay performed in the same laboratory the gpt and Spigenes were investigated in liver 90 days after the last injection (Suzuki et al, 2020). Louro et al (2014) treated intravenously C57BL/6 transgenic mice and analysed LacZ mutations in liver and spleen.…”

Section: In Vivo Gene Mutation Studiesmentioning

confidence: 99%

Safety assessment of titanium dioxide (E171) as a food additive

Flavourings¹,

Younes²,

Aquilina³

et al. 2021

EFS2

117

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The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO 2 nanoparticles ( NP s) and data from an extended one‐generation reproductive toxicity ( EOGRT ) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO 2 NP s < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO 2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO 2 NP s (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO 2 NP s, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO 2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico‐chemical properties of TiO 2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO 2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO 2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut‐off value for TiO 2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO 2 NP s. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.

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Section: In Vivo Gene Mutation Studiesmentioning

confidence: 99%

Safety assessment of titanium dioxide (E171) as a food additive

Flavourings¹,

Younes²,

Aquilina³

et al. 2021

EFS2

117

View full text Add to dashboard Cite

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“…Titanium dioxide nanoparticles (TiO2NPs) possess interesting photocatalytic properties, such as the ability to mediate the photolysis of pharmaceuticals, inactivating bacteria, and the effect of photo-oxidative killing on cancer cells, energy storage, in addition to air and water purification, and other uses (2). TiO2NPs are increasingly being manufactured in large quantities for industrial applications such as cosmetics, dyes, foods, and photocatalysts (3). They are used in water, sewage, and gas combustion treatment as an anti-bacterial material for decontamination and a cofactor in organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Histopathological effects of titanium dioxide nanoparticles on the liver of Japanese quail Coturnix coturnix japonica

Ahmed¹,

Taha²

2022

IJVS

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Titanium dioxide nanoparticles have multiple beneficial uses, as they are used in many medical, industrial, economic, and other fields. Despite these many benefits, it is not without harm to humans and animals if used without control. Therefore, the present study aimed to discover the histopathological effects of Titanium dioxide nanoparticles on the liver of Japanese quail, Coturnix coturnix japonica. The study included three groups, the first group, the control group, which were dosed with distilled water for four continuous days, and the second and third experimental groups, which were dosed with Titanium dioxide nanoparticles at a concentration of 20 and 40 mg/kg, respectively. Four, fourteen, thirty and sixty days after the experiment began, the birds were sacrificed. The results showed the emergence of many histological lesions in the liver of birds of the two experimental groups, to varying degrees, in the four periods, among the most prominent tissue lesions that appeared in the second experimental group, the emergence of necrosis, hemorrhage, vacuolation, congestion, ballooning swelling, in addition to infiltration of inflammatory cells. While in the third experimental group, histopathological lesions appeared similar to second group, in addition to sinuses dilatation, Kupffer cells hypertrophy, hepatocyte enlargement, and necrosis of the walls of blood vessels and bile ducts. The study concluded that direct exposure to Titanium dioxide nanoparticles leads to damage to the liver tissue of these birds, which may affect its function and thus endanger its life.

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“…In vivo studies in rodents exposed to TiO 2 reported toxic effects such as inflammation, impairment of biological barrier functions (intestinal, placental, blood-testis), as well as the promotion of cancer development [ 7 , 10 , 11 ]. Overall, repeated exposure to these particles exhibiting cytotoxic, genotoxic and immunotoxic effects is considered to be an important health issue [ 12 – 14 ]. For the general population, there is accumulating evidence that the main uptake route is ingestion, since TiO 2 is produced at high volumes as a food grade pigment (E171 in EU) incorporated in many foodstuffs as well as in toothpaste, medicines and food supplements.…”

Section: Introductionmentioning

confidence: 99%

Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model

et al. 2020

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Background Titanium dioxide (TiO2) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO2 nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO2-NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus. However, no human data are available for pregnant women exposed to food-grade TiO2-NPs and their potential transfer to the foetus. In this study, human placentae collected at term from normal pregnancies and meconium (the first stool of newborns) from unpaired mothers/children were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and scanning transmission electron microscopy (STEM) coupled to energy-dispersive X-ray (EDX) spectroscopy for their titanium (Ti) contents and for analysis of TiO2 particle deposition, respectively. Using an ex vivo placenta perfusion model, we also assessed the transplacental passage of food-grade TiO2 particles. Results By ICP-MS analysis, we evidenced the presence of Ti in all placentae (basal level ranging from 0.01 to 0.48 mg/kg of tissue) and in 50% of the meconium samples (0.02–1.50 mg/kg), suggesting a materno-foetal passage of Ti. STEM-EDX observation of the placental tissues confirmed the presence of TiO2-NPs in addition to iron (Fe), tin (Sn), aluminium (Al) and silicon (Si) as mixed or isolated particle deposits. TiO2 particles, as well as Si, Al, Fe and zinc (Zn) particles were also recovered in the meconium. In placenta perfusion experiments, confocal imaging and SEM-EDX analysis of foetal exudate confirmed a low transfer of food-grade TiO2 particles to the foetal side, which was barely quantifiable by ICP-MS. Diameter measurements showed that 70 to 100% of the TiO2 particles recovered in the foetal exudate were nanosized. Conclusions Altogether, these results show a materno-foetal transfer of TiO2 particles during pregnancy, with food-grade TiO2 as a potential source for foetal exposure to NPs. These data emphasize the need for risk assessment of chronic exposure to TiO2-NPs during pregnancy.

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

Cited by 13 publications

References 27 publications

Safety assessment of titanium dioxide (E171) as a food additive

Safety assessment of titanium dioxide (E171) as a food additive

Histopathological effects of titanium dioxide nanoparticles on the liver of Japanese quail Coturnix coturnix japonica

Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model

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