Review of potential health risks associated with nanoscopic calcium phosphate

Epple, Matthias

doi:10.1016/j.actbio.2018.07.036

Cited by 140 publications

(125 citation statements)

References 178 publications

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“…Additionally, it should be highlighted that once the HAP-NP 3.1% suspension (an opaque suspension) is added to the SGF, the dissolution is almost instantaneous leading to a clear solution without any observation of the opacity caused by the HAP-NP particles suspension. This reinforces the conclusion about the safety of the HAP-NP in the case of ingestion, since it will dissolve instantaneously in its Ca 2+ and PO 4 2− ions, in agreement with the Epple's statement that rules out any adverse health effect by an oral exposition to calcium phosphate [25]. Therefore, the possibility of HAP-NP absorption by intestinal cells after accidental ingestion was also discarded.…”

Section: Discussionsupporting

confidence: 85%

“…A safety assessment using mucosa-like human corneal epithelial (HCE) tissue model-using human corneal keratinocytes-has also demonstrated similar results, with a lack of cytotoxicity and no changes in IL-1 alpha release [22]. Usually, safety studies are performed using 2D cell culture models, such as human buccal epithelial cells [23], 3T3 fibroblasts [22] on osteoblast-like cells [24] using different crystallographic nature of the HAP-NP, which can induce different cell responses, as reviewed by Epple [25].…”

Section: Discussionmentioning

confidence: 94%

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Safety Assessment of Nano-Hydroxyapatite as an Oral Care Ingredient according to the EU Cosmetics Regulation

et al. 2018

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Hydroxyapatite nanoparticles (HAP-NP) are incorporated in oral care products such as toothpastes and mouthwashes to treat dental sensitivity or to promote enamel remineralisation. Despite the good performance of HAP-NP in this application, it is important to ensure its safety for consumers. For that reason, the Scientific Committee on Consumer Safety (SCCS) evaluated the safety of HAP-NP as an oral care ingredient, but the issued opinion was not completely conclusive and the SCCS recommended that additional tests should be performed. Here, we used a commercially available human gingival epithelium (HGE) as a non-animal alternative and MTT cell viability, LDH activity, and IL-1alpha production were evaluated after 3.1% HAP-NP treatment for 10 min, 1 h, and 3 h. Moreover, the absorption of HAP-NP in the gingival tissue was assessed by transmission electron microscopy (TEM) analysis. Finally, the dissolution behaviour of HAP-NP in simulated gastric fluid was also investigated. No deleterious effect was observed for HGE tissues incubated with HAP-NP for all time-points and parameters evaluated. Moreover, a complete dissolution of 3.1% HAP-NP in simulated gastric fluid was observed after 7.5 min at 37 °C. In conclusion, our results evidence the safety of HAP-NP for oral care products with the use of an in vitro replacement alternative for human gingival epithelium and a simulated gastric fluid assay.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 94%

Safety Assessment of Nano-Hydroxyapatite as an Oral Care Ingredient according to the EU Cosmetics Regulation

et al. 2018

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“…11 Biomimetic ingredients based on HAP used in oral care show a high compatibility, since the mineral phase of the teeth and bones mainly consists of calcium and phosphate. 32,33…”

Section: Discussionmentioning

confidence: 99%

In Vitro Whitening Effect of a Hydroxyapatite-Based Oral Care Gel

et al. 2020

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Objective Oral care formulations aim to prevent oral diseases such as dental caries and gingivitis. Additionally, desire for white teeth still exists across all age groups. It is known that most whitening toothpastes are highly abrasive and can be harmful to teeth and gingiva. Therefore, a gel formulation with biomimetic hydroxyapatite (HAP; Ca5[PO4]3[OH]) as active ingredient was developed. This formulation was tested with respect to its tooth whitening properties in an in vitro study. Materials and Methods Enamel samples were allocated to either group (a) HAP gel, (b) whitening mouth rinse phosphates, or (c) negative control (distilled water). Test products were applied by finger (a) or were rinsed (b, c) for 1, 3, and 9 (b and c only) cycles, respectively. Results Color changes (ΔE) were measured spectrophotometrically. Group (a) showed a significant increase in color changes with respect to whitening after one cycle (mean ΔE = 5.4 [±2.66], p ≤ 0.006) and three cycles (mean ΔE = 11.2 [±3.11], p < 0.0001) compared to groups (b) and (c). For group (b), a significant increase in color change was measured after three (mean ΔE = 2.77 [±1.01], p = 0.02) and nine cycles (mean ΔE = 3.27 [±1.61], p = 0.006) compared to (c). Group (c) showed only minor and statistically insignificant color changes. Conclusion This in vitro study demonstrated a significantly higher ad hoc whitening effect of the HAP gel compared to the mouth rinse and water after short-time application.

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“…12 Its application, in any reasonable dose, does not pose any risks for a patient's health. 13 HAP particles interact with enamel surfaces as shown in vitro, 14 in situ, 15 and in vivo. 16,17 Clinical studies have shown effects of HAP-based toothpastes, for example, in prevention of enamel caries 17 and reducing dentin hypersensitivity, 18 as well as in improving periodontal health.…”

Section: Introductionmentioning

confidence: 88%

In Vivo Effects of a Hydroxyapatite-Based Oral Care Gel on the Calcium and Phosphorus Levels of Dental Plaque

Sudradjat¹,

Meyer

Loza

et al. 2020

Eur J Dent

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Objectives Particulate hydroxyapatite (HAP; Ca5(PO4)3(OH)) is a biomimetic oral care ingredient. One mode of action in caries-susceptible individuals may be the adhesion/incorporation of HAP into dental plaque. Therefore, the aim of this in vivo study was to analyze the 3-day effects of a newly developed hydroxyapatite-based oral care gel on the calcium and phosphorus levels within the dental plaque of children. Materials and Methods This study was conducted in Kebon Padangan at Bali in Indonesia. Thirty-four children (mean age, 8.9 years; mean DMF-T [decayed, missing, and filled teeth; permanent teeth], 0.6; mean dmft-t [primary teeth] 4.5) were included in the study. The gel was applied thrice for 3 days by an experienced dentist. Dental plaque was collected at baseline and after the study. Levels of calcium and phosphorus of plaque samples were analyzed by energy-dispersive X-ray spectroscopy. Statistical Analysis Medians for both calcium and phosphorus levels were calculated (baseline and 3-day application of HAP-gel). Results The calcium level increased after 3 days of application of the HAP-gel from 0.25 wt% (median) to 0.40 wt% (median), while the phosphorus level increased from 1.17 wt% (median) to 1.41 wt% (median). However, variations in both calcium and phosphorus levels measured in the pooled dental plaque samples were high. Conclusion Within the limitations of the study, the 3-day application of the oral HAP-gel in children increased the median of both calcium and phosphorus levels in plaque. Consequently, a positive influence on the remineralization/demineralization process is very likely.

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Review of potential health risks associated with nanoscopic calcium phosphate

Cited by 140 publications

References 178 publications

Safety Assessment of Nano-Hydroxyapatite as an Oral Care Ingredient according to the EU Cosmetics Regulation

Safety Assessment of Nano-Hydroxyapatite as an Oral Care Ingredient according to the EU Cosmetics Regulation

In Vitro Whitening Effect of a Hydroxyapatite-Based Oral Care Gel

In Vivo Effects of a Hydroxyapatite-Based Oral Care Gel on the Calcium and Phosphorus Levels of Dental Plaque

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