Abstract

BackgroundTitanium 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.ResultsBy 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.ConclusionsAltogether, 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.

Highlights

  • Titanium dioxide (TiO2) is one of the most commonly produced nanomaterials used for various industrial applications based on its colouring and opacifying properties as well as its photocatalytic and biocidal activities [1, 2]

  • Physico-chemical characteristics of food-grade TiO2 particles scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) analyses showed that E171 had TiO2 particles with a mean particle size of 104.9 ± 44.9 nm and a particle size distribution ranging from 20 to 440 nm, with 55% of NPs by number (Table 1 and Fig. 1)

  • inductively coupled plasma mass spectrometry (ICP-MS) measurement of total Ti content in the human term placenta and the meconium, and particle analysis by scanning transmission electron microscopy (STEM)-EDX As shown in Table 2, Ti was found in all placental samples (n = 22), with the total Ti content ranging from 0.01 to 0.48 mg/kg of tissue

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Summary

Introduction

Titanium dioxide (TiO2) is one of the most commonly produced nanomaterials used for various industrial applications (cosmetics, water and soil treatment, UV filter, medicine, food sector) based on its colouring and opacifying properties as well as its photocatalytic and biocidal activities [1, 2] Due to these widespread applications, including in food, human exposure to TiO2 nanoparticles (NPs, at least one dimension < 100 nm) occurs by inhalation, dermal exposure and the oral route. Oral kinetic studies in human volunteers showed that a fraction of food-grade TiO2 is absorbed and reaches the bloodstream a few hours after ingestion [5] In this context, maternal exposure during pregnancy has not yet been evaluated for risk assessment in humans. Using an ex vivo placenta perfusion model, we assessed the transplacental passage of food-grade TiO2 particles

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