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

Guillard, A; Gaultier, Eric; Cartier, Christel; Devoille, Laurent; Noireaux, J; Chevalier, Laetitia; Morin, Mathieu; Grandin, Flore C.; Lacroix, Marlène Z.; Coméra, Christine; Cazanave, A; Place, Alice de; Gayrard, Véronique; Bach, Véronique; Chardon, Karen; Bekhti, Nihel; Adel‐Patient, Karine; Vayssière, Christophe; Fisicaro, Paola; Feltin, Nicolas; Farge, F. De La; Picard‐Hagen, Nicole; Lamas, Bruno; Houdeau, Eric

doi:10.1186/s12989-020-00381-z

Cited by 61 publications

(67 citation statements)

References 68 publications

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“…( 2015 ) E 171, anatase, d50 = 260 nm1Qualitative analysis in blood, methodology highly reliable Guillard et al. ( 2020 ) E 171, anatase, 20–440 nm (mean 104.9 nm (SEM‐EDX), 55% nanoparticles1Quantitative analysis in tissues, methodology reliable with some limitations Disdier et al. ( 2015 ) TiO 2 NPs, P25 (15–24 nm)1Quantitative analysis in blood and tissues, methodology reliable with some limitations Kreyling et al.…”

Section: Appendix G – Description Of Test Materials Scoring For Nanoscale Consideration and Internal Exposure For Toxicokinetic Studiesmentioning

confidence: 99%

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

Flavourings¹,

Younes²,

Aquilina³

et al. 2021

EFS2

120

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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: Appendix G – Description Of Test Materials Scoring For Nanoscale Consideration and Internal Exposure For Toxicokinetic Studiesmentioning

confidence: 99%

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

Flavourings¹,

Younes²,

Aquilina³

et al. 2021

EFS2

120

View full text Add to dashboard Cite

show abstract

“…However, placenta perfusion experiments with E171 suspension confirmed a low transfer of food-grade TiO 2 particles to the fetal side. The diameter of the TiO 2 particles recovered in the fetal exudate showed that 70 to 100% of particles were in the nanosized range [ 77 ]. These findings suggest that the human placenta barrier is not able to completely prevent the passage of TiO 2 nanoparticles to the fetus and emphasized the need to assess the risk of TiO 2 nanoparticles during pregnancy [ 77 ].…”

Section: Toxicokinetics Of Ingested E171mentioning

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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“…The possible reason might be different sizes for adopted TiO 2 NPs. The maternal-fetal transfer and accumulation of food-grade TiO 2 NPs in the human placenta and meconium emphasized the need for the risk assessment of chronic exposure to TiO 2 -NPs during pregnancy [75]. The protocol for black carbon detection in the placenta and evidence of them at the fetal side of human placenta.…”

Section: Introductionmentioning

confidence: 99%

Fetotoxicity of Nanoparticles: Causes and Mechanisms

et al. 2021

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The application of nanoparticles in consumer products and nanomedicines has increased dramatically in the last decade. Concerns for the nano-safety of susceptible populations are growing. Due to the small size, nanoparticles have the potential to cross the placental barrier and cause toxicity in the fetus. This review aims to identify factors associated with nanoparticle-induced fetotoxicity and the mechanisms involved, providing a better understanding of nanotoxicity at the maternal–fetal interface. The contribution of the physicochemical properties of nanoparticles (NPs), maternal physiological, and pathological conditions to the fetotoxicity is highlighted. The underlying molecular mechanisms, including oxidative stress, DNA damage, apoptosis, and autophagy are summarized. Finally, perspectives and challenges related to nanoparticle-induced fetotoxicity are also discussed.

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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

Cited by 61 publications

References 68 publications

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

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

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

Fetotoxicity of Nanoparticles: Causes and Mechanisms

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