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

Abstract

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.

Nanoparticles as Anti-Microbial, Anti-Inflammatory, and Remineralizing Agents in Oral Care Cosmetics: A Review of the Current Situation

“…Moreover, after 7.5 min at 37 • C, the complete dissolution of 3.1% HA NPs in simulated gastric fluid was observed. These results confirmed the safety of HA NPs for oral care products [241].…”

“…The Scientific Committee on Consumer Safety analyzed the safety of HA NPs as an oral care ingredient, but the results were not informative enough. Ramis and colleagues proved from in vitro experiments that no deleterious effects were noticed for human gingival epithelium tissues incubated with HA NPs at all evaluated time-points and parameters [241]. Moreover, after 7.5 min at 37 • C, the complete dissolution of 3.1% HA NPs in simulated gastric fluid was observed.…”

“…HA NPs have been integrated into products for oral care such as dentifrices and mouthwash to reduce or delete dental sensitivity by obstructing open dentinal tubules on the surface of the dentin and connected to the pulp, or for the purpose of promoting the remineralization of enamel by replacing calcium and phosphate ions in the areas from which minerals dissolved, restoring its integrity and shine [238][239][240][241]. In 2006, in Europe, HA NP dentifrice was instituted to facilitate remineralization and restoration of enamel [179].…”

“…In 2006, in Europe, HA NP dentifrice was instituted to facilitate remineralization and restoration of enamel [179]. In accordance with the producer, the maximal incorporation of this 15.5% HA NP aqueous suspension oral care ingredient is 20% in a dentifrice and 10% in a mouthwash [241].…”

<p>Development of an Experimental Dentifrice with Hydroxyapatite Nanoparticles and High Fluoride Concentration to Manage Root Dentin Demineralization</p>

“…The formulations were produced with the constituents commonly present in dentifrices and the absence of significant difference after nano-HA addition is justified by the biocompatibility of this substance, which corroborates the safety of hydroxyapatite nanoparticles for oral care products. 40 A pH cycling model was used to simulate the mineral loss and gain that occur in the oral cavity. This model is able to mimic the dynamic conditions of the oral cavity and, therefore, provides important data on in vitro models.…”