Calcium phosphate is applied in many products in biomedicine, but also in toothpastes and cosmetics. In some cases, it is present in nanoparticulate form, either on purpose or after degradation or mechanical abrasion. Possible concerns are related to the biological effect of such nanoparticles. A thorough literature review shows that calcium phosphate nanoparticles as such have no inherent toxicity but can lead to an increase of the intracellular calcium concentration after endosomal uptake and lysosomal degradation. However, cells are able to clear the calcium from the cytoplasm within a few hours, unless very high doses of calcium phosphate are applied. The observed cytotoxicity in some cell culture studies, mainly for unfunctionalized particles, is probably due to particle agglomeration and subsequent sedimentation onto the cell layer, leading to a very high local particle concentration, a high particle uptake, and subsequent cell death. There is no risk from an oral uptake of calcium phosphate nanoparticles due to their rapid dissolution in the stomach. The risk from dermal or mucosal uptake is very low. Calcium phosphate nanoparticles can enter the bloodstream by inhalation, but no adverse effects have been observed, except for a prolonged exposition to high particle doses. Calcium phosphate nanoparticles inside the body (e.g. after implantation or due to abrasion) do not pose a risk as they are typically resorbed and dissolved by osteoclasts and macrophages. There is no indication for a significant influence of the calcium phosphate phase or the particle shape (e.g. spherical or rod-like) on the biological response. In summary, the risk associated with an exposition to nanoparticulate calcium phosphate in doses that are usually applied in biomedicine, health care products, and cosmetics is very low and most likely not present at all.

Statement of significance

Calcium phosphate is a well-established biomaterial. However, there are occasions when it occurs in a nanoparticulate form (e.g. as nanoparticle or as nanoparticulate bone substitution material) or after abrasion from a calcium phosphate-coated metal implant. In the light of the current discussion on the safety of nanoparticles, there have been concerns about potential adverse effects of nano-calcium phosphate, e.g. in a statement of a EU study group from 2016 about possible dangers associated with non-spherical nano-hydroxyapatite in cosmetics. In the US, there was a discussion in 2016 about the dangers of nano-calcium phosphate in babyfood.

In this review, the potential exposition routes for nano-calcium phosphate are reviewed, with special emphasis on its application as biomaterial.

中文翻译：

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审查与纳米磷酸钙相关的潜在健康风险

磷酸钙不仅可用于生物医学的许多产品中，而且还可用于牙膏和化妆品中。在某些情况下，故意或降解或机械磨损后以纳米颗粒形式存在。可能的担忧与此类纳米颗粒的生物学效应有关。详尽的文献综述表明，磷酸钙纳米粒子本身没有内在的毒性，但可导致内体摄取和溶酶体降解后细胞内钙浓度增加。但是，除非施加非常高剂量的磷酸钙，否则细胞能够在数小时内从细胞质中清除钙。在某些细胞培养研究中观察到的细胞毒性（主要是针对未官能化的颗粒）可能是由于颗粒团聚并随后沉淀到细胞层上所致，导致非常高的局部颗粒浓度，很高的颗粒吸收以及随后的细胞死亡。由于磷酸钙纳米粒子在胃中的快速溶解，因此口服吸收没有风险。真皮或粘膜摄取的风险非常低。磷酸钙纳米颗粒可以通过吸入进入血液，但是除了长时间暴露于高剂量的颗粒外，没有观察到任何不利影响。体内的磷酸钙纳米粒子（例如植入后或由于磨损）不会造成危险，因为它们通常会被破骨细胞和巨噬细胞吸收和溶解。没有迹象表明磷酸钙相或颗粒形状（例如球形或棒状）对生物学反应有重大影响。总之，

重要声明

磷酸钙是一种公认​​的生物材料。但是，有时会以纳米颗粒的形式（例如，作为纳米颗粒或作为纳米颗粒的骨替代材料）或在被磷酸钙涂层的金属植入物磨蚀后发生。根据当前有关纳米粒子安全性的讨论，人们一直担心纳米磷酸钙的潜在不利影响，例如，欧盟研究小组在2016年发表的一份声明中谈到，纳米粒子中非球形纳米羟基磷灰石可能存在的危险。化妆品。在美国，2016年对婴儿食品中纳米磷酸钙的危害进行了讨论。

在这篇综述中，综述了纳米磷酸钙的潜在暴露途径，特别强调了其作为生物材料的应用。