Biokinetics of engineered nano-TiO<sub>2</sub> in rats administered by different exposure routes: implications for human health

Bello, Dhimiter; Warheit, David B.

doi:10.1080/17435390.2017.1330436

Cited by 23 publications

(22 citation statements)

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“…Recently, very low oral (0.02 and 0.6%) absorption of TiO 2 nanoparticles has been shown in rats, with a retention of these particles in mainly the liver and spleen [ 11 , 12 ]. This calls for (nano)particle biokinetic studies in humans [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Detection of titanium particles in human liver and spleen and possible health implications

et al. 2018

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BackgroundTitanium dioxide (TiO2) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO2 to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO2 particle consumption could not be excluded then.ResultsHere we show the first quantification of both total titanium (Ti) and TiO2 particles in 15 post-mortem human livers and spleens. These low-level analyses were enabled by the use of fully validated (single particle) inductively coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods for total Ti and TiO2 particles. The presence of TiO2 in the particles in tissues was confirmed by Scanning Electron Microscopy with energy dispersive X-ray spectrometry.ConclusionsThese results prove that TiO2 particles are present in human liver and spleen, with ≥24% of nanosize (< 100 nm). The levels are below the doses regarded as safe in animals, but half are above the dose that is deemed safe for liver damage in humans when taking into account several commonly applied uncertainty factors. With these new and unique human data, we remain with the conclusion that health risks due to oral exposure to TiO2 cannot be excluded.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0251-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Detection of titanium particles in human liver and spleen and possible health implications

et al. 2018

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“…A large body of in vivo and in vitro particle toxicology and nanotoxicology studies have shown that nanoparticles induce toxicity via a number of mechanisms, including intracellular reactive oxygen species (ROS) generation and ensuing oxidative stress, Ca 2+ flux, induction of pro-inflammatory mediators through receptor stimulation, hypersensitivity, genotoxicity, and cell necrosis [ 15 , 16 , 17 , 18 ]. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites

et al. 2018

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Researchers in nanocomposite processing may inhale a variety of chemical agents, including nanoparticles. This study investigated airway oxidative stress status in the exhaled breath condensate (EBC). Nineteen employees (42.4 ± 11.4 y/o), working in nanocomposites research for 18.0 ± 10.3 years were examined pre-shift and post-shift on a random workday, together with nineteen controls (45.5 ± 11.7 y/o). Panels of oxidative stress biomarkers derived from lipids, nucleic acids, and proteins were analyzed in the EBC. Aerosol exposures were monitored during three major nanoparticle generation operations: smelting and welding (workshop 1) and nanocomposite machining (workshop 2) using a suite of real-time and integrated instruments. Mass concentrations during these operations were 0.120, 1.840, and 0.804 mg/m3, respectively. Median particle number concentrations were 4.8 × 104, 1.3 × 105, and 5.4 × 105 particles/cm3, respectively. Nanoparticles accounted for 95, 40, and 61%, respectively, with prevailing Fe and Mn. All markers of nucleic acid and protein oxidation, malondialdehyde, and aldehydes C6–C13 were elevated, already in the pre-shift samples relative to controls in both workshops. Significant post-shift elevations were documented in lipid oxidation markers. Significant associations were found between working in nanocomposite synthesis and EBC biomarkers. More research is needed to understand the contribution of nanoparticles from nanocomposite processing in inducing oxidative stress, relative to other co-exposures generated during welding, smelting, and secondary oxidation processes, in these workshops.

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“…TiO 2 particles were detected in human post-mortem liver and spleen, with ≥24% of NPs (Heringa et al, 2018). Consistently, oral absorption of TiO 2 NPs has been shown in rats (Bello & Warheit, 2017;Geraets et al, 2014;Kreyling et al, 2017). Thus, concerns have been raising on the health risks due to oral exposure to TiO 2 NPs .…”

Section: Introductionmentioning

confidence: 67%

Combined effect of titanium dioxide nanoparticles and glucose on the cardiovascular system in young rats after oral administration

Chen

Zhou

Wang

et al. 2018

J of Applied Toxicology

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Titanium dioxide nanoparticles (TiO2 NPs) have already been used as food additive in various products and are usually consumed with a considerable amount of sugar. Oral consumption of TiO2 NPs poses concerning health risks; however, research on the combined effect of ingested TiO2 NPs and glucose is limited. We examined young Sprague‐Dawley rats administrated TiO2 NPs orally at doses of 0, 2, 10 and 50 mg/kg body weight per day with and without 1.8 g/kg body weight glucose for 30 and 90 days. Heart rate, systolic and diastolic blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. The results showed that oral exposure to TiO2 NPs and high doses of glucose both could induce cardiovascular injuries. The toxic effects were dose‐, time‐ and gender‐dependent. The interaction effects between oral‐exposed TiO2 NPs and glucose existed and revealed to be antagonism in most of the biological parameters. However, toxic effects of the high‐dose glucose seemed to be more severe than TiO2 NPs and the interaction of TiO2 NPs with glucose. These results suggest that it may be more important to control the sugar intake than TiO2 NPs for protecting the health of TiO2 NP consumers.

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Biokinetics of engineered nano-TiO₂ in rats administered by different exposure routes: implications for human health

Cited by 23 publications

References 26 publications

Detection of titanium particles in human liver and spleen and possible health implications

Detection of titanium particles in human liver and spleen and possible health implications

Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites

Combined effect of titanium dioxide nanoparticles and glucose on the cardiovascular system in young rats after oral administration

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Biokinetics of engineered nano-TiO2 in rats administered by different exposure routes: implications for human health

Cited by 23 publications

References 26 publications

Detection of titanium particles in human liver and spleen and possible health implications

Detection of titanium particles in human liver and spleen and possible health implications

Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites

Combined effect of titanium dioxide nanoparticles and glucose on the cardiovascular system in young rats after oral administration

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Biokinetics of engineered nano-TiO₂ in rats administered by different exposure routes: implications for human health