Vasomotor dysfunction in human subcutaneous arteries exposed ex vivo to food-grade titanium dioxide

Jensen, Ditte Marie; Skovsted, Gry Freja; Lykkesfeldt, Jens; Dreier, Rasmus; Berg, Jais Oliver; Jeppesen, Jørgen; Sheykhzade, Majid; Loft, Steffen; Möller, Peter

doi:10.1016/j.fct.2018.07.015

Cited by 12 publications

(5 citation statements)

References 28 publications

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“…Examination of cardiotoxic effects of E171 and TiO 2 nanoparticles revealed effects on vasomotor function, including the increase of acetylcholine-induced vasorelaxation, serotonin-induced vasoconstriction, and nitroglycerin levels [111,112].…”

Section: Referencementioning

confidence: 99%

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Bischoff

Kok

Sijm

et al. 2020

IJMS

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Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

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Section: Referencementioning

confidence: 99%

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Bischoff

Kok

Sijm

et al. 2020

IJMS

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“…Aortic Cer and NT accumulation after exposure to ZnO NPs in this work is consistent with previous reports on aortic damage, reduced wall thickness, high NT immunoreactivity, oxidative stress, and impaired vasodilation in acetaminophen-exposed rats [ 56 ]. These mechanisms could explain how NPs cause vascular dysfunction in subcutaneous, coronary arteries and the aorta [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…TiO 2 NPs and ZnO NPs have been detected in blood, tissues, and several organs including the brain, heart, intestine, kidney, liver, lung, and stomach of mice and rats after inhalation, intraperitoneal, or oral exposure [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Exposure to TiO 2 NPs and ZnO NPs can cause vascular dysfunction in subcutaneous arteries, coronary arteries, and the aorta [ 13 , 14 ]; histological and functional changes in organs [ 15 , 16 ]; genotoxicity [ 17 ]; cytotoxicity [ 18 , 19 ]; inflammation [ 20 , 21 ]; and endoplasmic reticulum (ER) stress [ 22 , 23 ]. Depending on dose and physicochemical characteristics (components, charges, solubility, size, shape), TiO 2 NPs and ZnO NPs produce reactive oxygen species (ROS), including radical and non-radical species such as peroxynitrite, activating different signaling pathways, eventually altering multiple cellular processes including mitosis, apoptosis, or autophagy [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide

Bautista-Pérez,

Cano-Martínez,

Herrera-Rodríguez

et al. 2024

IJMS

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Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin–eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.

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“…ANSES () reported additional effects but did not consider them relevant for the safety assessment of the food additive: in vitro studies on the interaction between titanium dioxide and gut microbiota (Dudefoi et al., ; Radziwill‐Bienkowska et al., ; Talbot et al., ); in vivo study in rats and ex vivo in human subcutaneous artery segments suggesting that exposure to titanium dioxide (E 171) at high doses may lead to cardiovascular effects (Jensen et al., ,b), and in vitro studies investigating local inflammation in macrophages (Riedle et al., ).…”

Section: Anses Opinion April 2019mentioning

confidence: 99%

EFSA statement on the review of the risks related to the exposure to the food additive titanium dioxide (E 171) performed by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES)

2019

EFS2

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On 15 April 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on the risks related to the exposure to the food additive titanium dioxide (E 171) taking into account the most recent scientific studies available. Further to this publication, EFSA was requested by the European Commission to provide urgent scientific and technical assistance regarding the opinion issued by ANSES. In the ANSES opinion, 25 new relevant publications published between 2017 and 2019 were reviewed together with previous opinions by EFSA and ANSES and a systematic review on in vitro genotoxicity of nano titanium dioxide. In this statement, EFSA concludes that the ANSES opinion published in April 2019 does not identify any major new findings that would overrule the conclusions made in the previous two scientific opinions on the safety of titanium dioxide (E 171) as a food additive issued by the EFSA ANS Panel in 2016 and 2018. The ANSES opinion reiterates the previously identified uncertainties and data gaps, which are currently being addressed in the context of the follow‐up activities originating from the previous EFSA evaluations and their recommendations. In addition to the aspects for which the follow‐up work is currently ongoing, ANSES recommends further investigation of in vivo genotoxicity. EFSA considers this recommendation should be revisited once the ongoing work on the physico‐chemical characterisation of the food additive titanium dioxide (E 171) is completed.

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Vasomotor dysfunction in human subcutaneous arteries exposed ex vivo to food-grade titanium dioxide

Cited by 12 publications

References 28 publications

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide

EFSA statement on the review of the risks related to the exposure to the food additive titanium dioxide (E 171) performed by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES)

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