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.

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.

Magnetic iodixanol - a novel contrast agent and its early characterization.

AIMS: Contrast-induced nephropathy is a commonly encountered problem in clinical practice. The purpose of the study was to design and develop a novel contrast agent, which could be used to prevent contrast-induced nephropathy in the future. METHODS: In total, 20-220nm magnetic nanoparticles were conjugated with iodixanol, and their radio-opacity and magnetic properties were assessed thereafter. Scanning electron microscopy pictures were acquired. Thereafter, the nanoparticles conjugate was tested in cell culture (HUVEC cells), and Quantibody® assay was studied after cell treatment in 1:5 dilutions for 48h, compared with control. RESULTS: The conjugate preparation had an adequate radio-opacity. A 4mm magnetic bubble was attached to a bar magnet and the properties were studied. The magnetic bubble maintained its structural integrity in all angles including antigravity position. Scanning electron microscopy showed magnetic nanoparticles in all pictures and the particles are of 100-400nm agglomerates with primary particle sizes of roughly 20nm. 1:5 diluted particles had no effect on secretion of IL-1a, IL-1b, IL-4, IL-10, IL-13 and TNFa. Particles increased secretion of IL-8 from 24h and 48h. Secretion of IFNg was also increased when particles were added to the cells as early as 1h. Likewise, IL-6 was strongly secreted by HUVEC treated with particles from 24h incubation time. In contrast, the secretion of MCP-1 was slightly reduced on HUVEC treated with particles. CONCLUSION: There is potential for a novel iodixanol-magnetic nanoparticle conjugate to be used in cineradiography. Further investigations need to be performed to study its performance in vitro and in vivo.