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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
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2020-10-07 , DOI: 10.1186/s12989-020-00381-z
A Guillard 1 , E Gaultier 1 , C Cartier 1 , L Devoille 2 , J Noireaux 3 , L Chevalier 4 , M Morin 5 , F Grandin 1 , M Z Lacroix 6 , C Coméra 1 , A Cazanave 1 , A de Place 5 , V Gayrard 1 , V Bach 7 , K Chardon 7 , N Bekhti 8 , K Adel-Patient 8 , C Vayssière 5, 9 , P Fisicaro 3 , N Feltin 2 , F de la Farge 1 , N Picard-Hagen 1 , B Lamas 1 , E Houdeau 1
Affiliation  

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. 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. 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.

中文翻译:

人胎盘和胎粪中的基础钛水平以及离体胎盘灌注模型中食品级TiO 2纳米粒子的物-胎转移的证据

二氧化钛(TiO2)广泛用于普通消费品中,包括作为食品添加剂(欧洲的E171),用于着色和遮光。E171添加剂包含TiO2纳米颗粒(NPs),其中一部分被肠道吸收并积累在几个全身器官中。怀孕期间啮齿动物接触到TiO2-NPs会导致胎盘功能的改变和NPs的物-胎转移,这对胎儿都有毒性作用。但是,尚无人类数据可用于暴露于食品级TiO2-NPs并可能转移至胎儿的孕妇。在这个研究中,使用感应耦合等离子体质谱法(ICP-MS)和扫描电子显微镜(STEM)结合能量色散X-射线(EDX)光谱测定钛(Ti)含量并分析TiO2颗粒沉积。使用离体胎盘灌注模型,我们还评估了食品级TiO2颗粒的经胎盘通过。通过ICP-MS分析,我们证明了所有胎盘中钛的存在(基础水平范围为0.01至0.48 mg / kg组织)和50%的胎粪样品(0.02–1.50 mg / kg)中均存在Ti,表明存在胎粪。钛的胎儿通道。对胎盘组织的STEM-EDX观察证实,除铁(Fe)外,还存在TiO2-NPs,锡(Sn),铝(Al)和硅(Si)作为混合或隔离的颗粒沉积物。TiO2颗粒以及Si,Al,Fe和锌(Zn)颗粒也被回收到了胎粪中。在胎盘灌注实验中,共聚焦成像和胎儿渗出液的SEM-EDX分析证实了食品级TiO2颗粒向胎儿侧的转移少,而ICP-MS几乎无法定量。直径测量表明,在胎儿分泌液中回收的TiO2颗粒中有70%至100%是纳米级的。总而言之,这些结果表明,在怀孕期间TiO2颗粒会向胎儿转移,而食品级TiO2可能是胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。还从胎粪中回收了Si,Al,Fe和锌(Zn)颗粒。在胎盘灌注实验中,胎儿渗出液的共聚焦成像和SEM-EDX分析证实了食品级TiO2颗粒向胎儿侧的转移少,而ICP-MS几乎无法定量。直径测量表明,在胎儿分泌液中回收的TiO2颗粒中有70%至100%是纳米级的。总而言之,这些结果表明,在怀孕期间TiO2颗粒会向胎儿转移,而食品级TiO2可能是胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。还从胎粪中回收了Si,Al,Fe和锌(Zn)颗粒。在胎盘灌注实验中,共聚焦成像和胎儿渗出液的SEM-EDX分析证实了食品级TiO2颗粒向胎儿侧的转移少,而ICP-MS几乎无法定量。直径测量表明,在胎儿分泌液中回收的TiO2颗粒中有70%至100%是纳米级的。总而言之,这些结果表明,在怀孕期间TiO2颗粒会向胎儿转移,而食品级TiO2可能是胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。胎儿渗出液的共聚焦成像和SEM-EDX分析证实,食品级TiO2颗粒向胎儿侧的转移很少,而ICP-MS几乎无法定量。直径测量表明,在胎儿分泌液中回收的TiO2颗粒中有70%至100%是纳米级的。总而言之,这些结果表明,在怀孕期间TiO2颗粒会向胎儿转移,而食品级TiO2可能是胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。胎儿渗出液的共聚焦成像和SEM-EDX分析证实,食品级TiO2颗粒向胎儿侧的转移很少,而ICP-MS几乎无法定量。直径测量表明,在胎儿分泌液中回收的TiO2颗粒中有70%至100%是纳米级的。总而言之,这些结果表明,在怀孕期间TiO2颗粒会向胎儿转移,而食品级TiO2可能是胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。食品级TiO2可作为胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。食品级TiO2可作为胎儿暴露于NP的潜在来源。这些数据强调需要对怀孕期间长期接触TiO2-NP的风险进行评估。
更新日期:2020-10-07
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