Scientific Committee On Consumer Safety Research Articles

Investigation on the skin penetration of synthetic amorphous silica (SAS) used in cosmetic products

Synthetic amorphous silica (SAS) is used as additive in a variety of industrial applications for many decades and has been approved to be used in food, food contact materials, pharmaceuticals, and cosmetics. Due its internal structure, SAS is considered as a nanomaterial, thus it is affected by a general safety discussion. Based on the production process, SAS for cosmetic application is a nanomaterial by the EU Recommendation, although it was not considered as such, because the solely size-dependent definitions of the term “nanomaterial” emerged in recent times first in Recommendation 2011/696/EU. Therefore, former physicochemical and toxicological evaluations of SAS were already performed on nanomaterials, however, without being addressed as such. Safety concerns can only emerge if two criteria, (toxicological) hazard and exposure towards the substance is fulfilled at the same time. In case of SAS, the Scientific Committee on Consumer Safety (SCCS) challenged provided data to be insufficient to draw a conclusion regarding the safety of SAS and thus, requested further investigations, in particular by exploring skin penetration of particulate SAS.Investigation of specific particulate substances in skin penetration tests is an analytical challenge. The number of available analytical techniques that are capable to detect nanomaterials in complex matrices, like receptor fluids from skin penetration testing, are limited and still emerging. In the new studies, a comprehensive set of analytical techniques were used to investigate the skin penetration potential of SAS. Particle-sensitive, element and particle-specific combinations of techniques and different sample preparation procedures, that respected the particulate nature of SAS, were used to detect SAS in receptor fluids directly. In addition, electron microscopic techniques were used to examine different layers of skin to detect adsorbed SAS.The combination of Asymmetric Flow Field-Flow Fractionation (AF4) in combination with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for examination of receptor fluids and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (SEM/EDX) for examination of skin itself, were identified as suitable techniques for the detection of SAS in skin penetration tests. Data from literature was used to compare the results of the studies with the outcome of other test systems (other particles, other techniques). Both, the test results, and literature evaluation led to the conclusion, that SAS does not penetrate skin. Based on this outcome and local and systemic dermal toxicity review of SAS, it can be concluded that dermal application of SAS in cosmetic formulations is negligible.

The Skin Sensitisation of Cosmetic Ingredients: Review of Actual Regulatory Status.

All cosmetics products must be safe under foreseeable conditions of use. Allergenic responses are one of the most frequent adverse reactions noted for cosmetics. Thus, the EU cosmetics legislation requires skin sensitisation assessment for all cosmetics ingredients, including the regulated ones (for which the full toxicological dossier needs to be analysed by the Scientific Committee on Consumer Safety (SCCS)) and those (perceived as less toxic) which are assessed by industrial safety assessors. Regardless of who performs the risk assessment, it should be carried out using scientifically and regulatory body-accepted methods. In the EU, reference methods for chemical toxicity testing are defined in the relevant Annexes (VII-X) of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation. Recommendations for Skin Sensitization (Skin Sens) testing are provided in Annex VII, and this particular endpoint information is required for all EU-registered chemicals. Historically, in vivo animal and human methods have been used. Both raise ethical doubts, and some of them cause practical problems in the objective analysis of skin sensitising potency. Previous decades of huge effort have resulted in the regulatory acceptance of the alternative Skin Sens IATA (Integrated Approaches to Testing and Assessment) and NGRA (Next Generation Risk Assessment). Regardless of the testing issues, a serious sociological problem are observed within the market: the consumer assumes the presence of strong sensitisers in cosmetics formulations and insufficient risk management tools used by the industry. The present review aims to provide an overview of methods for assessing skin sensitisation. Additionally, it aims to answer the following question: what are the most potent skin sensitisers used in cosmetics? The answer considers the mechanistic background along with the actual regulatory status of ingredients and practical examples of responsible industry solutions in the area of risk management.

List of opinions of the Scientific Committee on Consumer Safety (SCCS) adopted and published January to December 2022.

List of opinions of the Scientific Committee on Consumer Safety (SCCS) adopted and published January to December 2022.

A multi-functional anti-aging moisturizer maintains a diverse and balanced facial skin microbiome

To assess the effect of a 28-day skincare regimen in healthy female subjects on the facial skin microbiome composition and to determine whether the skincare regimen including a gentle cleansing lotion, a multi-functional anti-aging moisturizer formulated with prebiotics and postbiotics at skin neutral pH, and bland sunscreen pushed the microbiome to a healthier state and improved skin aging measured by self-assessment and clinical photography. The study protocol was in accordance with the EU Scientific Committee on Consumer Safety (SCCS) guidance and met all international standards. In all, 25 female subjects between 35 and 65 years old with Fitzpatrick skin types I-VI, moderate crow's feet wrinkles and global face photodamage were enrolled. After 28 days, the skincare regimen improved microbial facial diversity and shifted the microbiota composition when compared to baseline. After 28 days, the skincare regimen treatment shifted the distribution of the facial skin microbiome, positively influencing the skin microbiome diversity and balance, to promote long-term skin health and protect from further skin aging. These results suggest that incorporating prebiotics and postbiotics into a skincare regimen may have a positive impact on the facial skin microbiome in healthy women.

Innovative In Vitro Strategy for Assessing Aluminum Bioavailability in Oral Care Cosmetics.

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste containing a greater amount of aluminum hydroxide than advised by the Scientific Committee on Consumer Safety (SCCS). To simulate in vitro toothpaste accidental ingestion, the INFOGEST model was employed, and the amount of aluminum was measured through the ICP-AES analysis. Tissue barrier integrity was analyzed by measuring transepithelial electric resistance, and the tissue architecture was checked through light microscopy. The margin of safety was also calculated. Overall, our results indicate that the acute exposure to aluminum accidentally ingested from toothpastes is safe for the final user, even in amounts higher than SCCS indications.

Occupational Exposure of Hairdressers to Airborne Hazardous Chemicals: A Scoping Review.

Introduction: Exposure to hazardous chemicals released during hairdressing activities from hair care products puts hairdressers at risk of adverse health effects. Safety assessments of hair products are mainly focused on consumers, but exposure for professional hairdressers might be substantially higher. Objective: To identify and assess available research data on inhalation exposures of professional hairdressers. Methods: A systematic search of studies between 1 January 2000 and 30 April 2021 was performed in Medline, Embase, Web of Science and in Cochrane registry, toxicological dossiers of the Scientific Committee on Consumer Safety (SCCS) of the European Commission as well as the German MAK Commission. Studies reporting quantitative data on airborne concentrations of chemicals in the hairdresser’s workplace were considered. The outcome was an airborne concentration of chemicals in the working environment, which was compared, when possible, with current occupational exposure limits (OEL) or guidance levels. Results: In total, 23 studies performed in 14 countries were included. The average number of hairdressing salons per study was 22 (range 1–62). Chemicals most frequently measured were formaldehyde (n = 8), ammonia (n = 5), total volatile organic compounds (TVOC) (n = 5), and toluene (n = 4). More than fifty other chemicals were measured in one to three studies, including various aromatic and aliphatic organic solvents, hydrogen peroxide, persulfate, and particulate matter. Most studies reported environmental air concentrations, while personal exposure was measured only in seven studies. The measured air concentrations of formaldehyde, ammonia, and TVOC exceeded OEL or guidance values in some studies. There was large variability in measuring conditions and reported air concentrations differed strongly within and between studies. Conclusion: Hairdressers are exposed to a wide spectrum of hazardous chemicals, often simultaneously. Airborne concentrations of pollutants depend on salon characteristics such as ventilation and the number of customers but also on used products that are often country- or client-specific. For exposure to formaldehyde, ammonia, and TVOC exceeding OELs or guidance values for indoor air was observed. Therefore, occupational exposure should be taken into account by safety regulations for hair care products.

List of opinions of the Scientific Committee on Consumer Safety (SCCS) adopted and published January to December 2021

List of opinions of the Scientific Committee on Consumer Safety (SCCS) adopted and published January to December 2021

Using Human Biomonitoring Data to Support Risk Assessment of Cosmetic Ingredients-A Case Study of Benzophenone-3.

Safety assessment of UV filters for human health by the Scientific Committee on Consumer Safety (SCCS) is based on the estimation of internal dose following external (skin) application of cosmetic products, and comparison with a toxicological reference value after conversion to internal dose. Data from human biomonitoring (HBM) could be very useful in this regard, because it is based on the measurement of real-life internal exposure of the human population to a chemical. UV filters were included in the priority list of compounds to be addressed under the European Human Biomonitoring Initiative (HBM4EU), and risk assessment of benzophenone-3 (BP-3) was carried out based on HBM data. Using BP-3 as an example, this study investigated the benefits and limitations of the use of external versus internal exposure data to explore the usefulness of HBM to support the risk assessment of cosmetic ingredients. The results show that both approaches did indicate a risk to human health under certain levels of exposure. They also highlight the need for more robust exposure data on BP-3 and other cosmetic ingredients, and a standardized framework for incorporating HBM data in the risk assessment of cosmetic products.

A Review of the EU’s Regulatory Framework for the Production of Nano-Enhanced Cosmetics

Literature has suggested metallic nanomaterials (NMs) for a multitude of applications in cosmetic products, either as active ingredients or excipients. Alike most high-paced industrial sectors, cosmetology continues to capitalize on its unique properties/functions (e.g., as UV-filters, colorants, etc.), adding value to a wide range of products. However, as a result of their nano-scale, NMs do not always conform with the handling guidelines of their bulk counterparts, nor do conventional analytical methods account for their complex physicochemical and biological interactions. Among others, metallic nanoparticles have attracted the interest of many over the years due to their unique features, but possible precautions should be considered because of their bio-persistent nature. As a result, it is prevalent to consider a nano-specific framework, to regulate the use of NMs and the production of nano-enhanced cosmetics. To address this, we provide insight into the NMs that are currently used in the EU market, with a focus on metallic NMs, while analyzing the underlying legislation and relevant Opinions of the Scientific Committee on Consumer Safety (SCCS), from a scientific and commercial perspective. Even though the current Cosmetics Regulation (EU Regulation No 1223/2009) already entails specific provisions on NMs, cosmetic products incorporating unauthorized NMs have been repeatedly commercialized in the European Union. Considering the potential risks of NMs if they are mishandled, we provide an analysis of the risk assessment, as stated in Article 16 of the Cosmetics Regulation, to serve as a guideline for the future growth of nano-enhanced products. Based on the limited integration of metallic NMs along with multiple non-metallic NPs into cosmetic products, the attention of the community is directed towards coordinating efforts on the integration of metallic NMs into cosmetics.

Ethylzingerone, a Novel Compound with Antifungal Activity.

Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of ethylzingerone (hydroxyethoxyphenyl butanone [HEPB]), an SCCS-approved new preservative for use in rinse-off, oral care, and leave-on cosmetic products. We show that HEPB significantly inhibits growth of Candida albicans, Candida glabrata, and Saccharomyces cerevisiae, acting fungicidally against C. albicans Using transcript profiling experiments, we found that the C. albicans transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that C. albicans phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded S. cerevisiae nonessential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The trp1Δ mutants in S. cerevisiae and C. albicans were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode of action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in the cosmetic industry, and exemplifies the powerful use of functional genomics to illuminate the mode of action of antimicrobial agents.

How high‐resolution mass spectrometry can help for the accurate quantification of difficult fragrance allergens

AbstractTwo high‐resolution mass spectrometers (HRMS) with different analyzer technology, Orbitrap and hybrid quadrupole time‐of‐flight (QTOF), were compared with a low‐resolution mass spectrometer, quadrupole, to analyse a set of 35 difficult allergens. These difficult allergens are commonly coeluted fragrance allergens with matrix compounds, using standard gas chromatography‐mass spectrometer conditions, from the extended list of the Scientific Committee on Consumer Safety (SCCS). Although the fundamental role of chromatographic separation has been demonstrated many times, the aim of this work is to demonstrate the benefits of high‐resolution. The added value of high‐resolution was illustrated in both a qualitative and a quantitative way. For qualitative aspect, the high resolution extracted ion signals of these two detectors were compared with the low‐resolution extracted ion signals. About 50% of the coeluted cases observed with the low‐resolution detector are easily resolved by the two high‐resolution detectors. For the quantitative aspect, an accuracy profile methodology and a performance metric were used to propose an overall evaluation. The Orbitrap mass spectrometer demonstrated a better overall performance, while the QTOF presented similar or even lower quantification performances than the quadrupole on the set of analysed fragrances.

Renewable sources: applications in personal care formulations.

A global tendency for products considered environmentally sustainable, and ecologically obtained led the industry related to personal care formulations to fund the research and the development of personal care/cosmetics containing ingredients from natural resources. Furthermore, consumers are aware of environmental and sustainability issueans, thus not harming the environment represents a key consideration when developing a new cosmetic ingredient. In this study we review some examples of active ingredients or raw materials used in cosmetics/personal care/biomedical products that are coming from either through biotechnological systems, or as byproducts of several industries. A skin formulation containing biosynthetic actives, prepared by us and the study regarding its dermocosmetic properties are also described. The need for the standardization processes, the safety assessment tools, the improvement of the exploitation methods of these renewable sources in order the production to be ecologically and economically better are also discussed.

Safety of titanium dioxide nanoparticles in cosmetics.

Titanium dioxide (TiO2 ) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano-TiO2 ) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano-TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano-TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano-TiO2 as a non-sensitizer and as mild- or non-irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano-TiO2 . According to the SCCS, nano-TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano-TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano-TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano-TiO2 absorption and toxicity are limited. The incidental oral exposure to nano-TiO2 contained in lip balms is thus not expected to induce adverse health effects.

Opinion of the Scientific Committee on Consumer safety (SCCS) – Opinion on the safety of cosmetic ingredient salicylic acid (CAS 69-72-7)

Opinion of the Scientific Committee on Consumer safety (SCCS) – Opinion on the safety of cosmetic ingredient salicylic acid (CAS 69-72-7)

Nano-hydroxyapatite in oral care cosmetics: characterization and cytotoxicity assessment

Nano-hydroxyapatite has been used as an oral care ingredient, being incorporated in several products for the treatment of dental hypersensitivity and enamel remineralisation. Despite its promising results, regulatory and safety concerns have been discussed and questioned by the European Scientific Committee on Consumer Safety (SCCS) regarding the usage of hydroxyapatite nanoparticles in oral care products. In this work, a commercially available nano-hydroxyapatite was characterized and its cytocompatibility towards human gingival fibroblasts was evaluated, as well as its irritation potential using the in vitro HET-CAM assay. All the conditions chosen in this study tried to simulate the tooth brushing procedure and the hydroxyapatite nanoparticles levels normally incorporated in oral care products. The commercial hydroxyapatite nanoparticles used in this study exhibited a rod-like morphology and the expected chemical and phase composition. The set of in vitro cytotoxicity parameters accessed showed that these nanoparticles are highly cytocompatible towards human gingival fibroblasts. Additionally, these nanoparticles did not possess any irritation potential on HET-CAM assay. This study clarifies the issues raised by SCCS and it concludes that this specific nano-hydroxyapatite is cytocompatible, as these nanoparticles did not alter the normal behaviour of the cells. Therefore, they are safe to be used in oral care products.

Opinion of the Scientific Committee on consumer safety (SCCS) – Final opinion on the safety of fragrance ingredient Acetylated Vetiver Oil (AVO) - (Vetiveria zizanioides root extract acetylated) - Submission III

On the basis of the safety assessment carried out using a conservative approach, the SCCS considers the use of Acetylated Vetiver Oil (AVO) with 1% alpha-tocopherol as a fragrance ingredient in cosmetic leave-on and rinse-off type products safe at the concentrations proposed by IFRA.Acetylated Vetiver Oil (AVO) contains some constituents that belong to the chemical group of aldehydes and ketones that are known to be reactive towards biological entities, such as DNA and proteins. However, the overall health risk of such components is likely to be negligible at the concentrations intended to be used in cosmetics products.The SCCS has noted that Acetylated Vetiver Oil (AVO) is a moderate skin sensitiser in test animals. Considering the results of the HRIPT study and the fact that AVO has been used for years in cosmetics without evidence of sensitising potential, it is unlikely that AVO would be causing contact allergy in humans.Inhalation toxicity of Acetylated Vetiver Oil (AVO) was not assessed in this Opinion because no data were provided. Assessment of the inhalation risk would be needed if Acetylated Vetiver Oil (AVO) was intended to be used in sprayable products.

Consumer protection and risk assessment: sensitising substances in consumer products

The human immune system is confronted daily with a large, chemically-varied range of potentially sensitising substances. Skin sensitising substances are found, above all, in a plethora of consumer products, e. g. cosmetics, jewellery, earrings, toys, textiles, leather, other everyday commodities and, in some cases, also tattoos. These products may contain sensitisers such as fragrances, preservatives, dyes, or other additives. To provide a greater degree of consumer protection, there is a need for specific legal regulation and risk assessment, which covers each possible human exposure to a sensitising substance or mixture. This review article describes the background and pathway towards the development and implementation of an international legal framework for the classification and labelling of chemicals that contain potentially skin sensitising substances. This includes the implementation of the globally harmonized system of classification and labelling of chemicals (GHS), the classification, labelling and packaging (CLP) regulation, registration, evaluation, authorisation and restriction of chemicals (REACH), and the regulation of cosmetics, among other national laws and regulations. Assessment criteria for classification is derived from a suite of in vitro and in vivo assays, in addition to in silico approaches—validated by the organisation for economic cooperation and development (OECD)—as well as data derived from human studies. New legislation for chemical and product safety is reflected in the classification and labelling of skin sensitising substances under Category 1, Subcategory 1A or 1B, within which the threshold concentrations of several materials are regulated, e. g. p‑phenylenediamine in hair dyes, nickel in piercings, chromium VI in leather and methylisothizolinone in cosmetics. In order to minimise the risk of human contact allergy from consumer products, the scientific committee on consumer safety (SCCS) and the German federal institute for risk assessment (BfR) investigate pathways of exposure and perform risk assessments using new in vitro approaches and new (immuno-) toxicological concepts (i. e. adverse outcome pathways [AOPs], key events as well as an integrated approach to testing and assessment [IATA]). In comparison to cosmetics, substances in textiles and other consumer products are less regulated. Major efforts in research and development are necessary to decode complex substance-specific molecular mechanisms in allergic responses and to define new substance-specific thresholds. Such efforts have been continuously proposed by the BfR with regard to fragrances for over 10 years. Today, skin sensitising substances can be legally regulated and labelled and, depending on the exposure, their content in consumer products can be reduced or eliminated. Furthermore, the risk assessment of potentially sensitising substances makes consumer products safer. Further improvements in research approaches are required in the area of health and consumer protection with regard to allergy.

Opinion of the Scientific Committee on Consumer safety (SCCS) – Final opinion on water-soluble zinc salts used in oral hygiene products

The SCCS has estimated that exposure to water-soluble zinc salts via toothpaste and mouthwash at the concentrations of 1 and 0.1%, respectively, may lead to a daily intake level of 3.54 mg for adults and children aged 6–17 years. This exposure constitutes between 14 and 35% of the Upper Limit (UL) for these age groups. Therefore, the SCCS considers that the use of zinc in toothpaste and mouthwash per se is safe for adults and children aged 6–17 years.The SCCS has estimated that exposure to water-soluble zinc salts via toothpaste at the concentrations of 1% may lead to a daily intake level of 1.0–2.00 mg for children aged 0.5–5 years. This exposure constitutes between 10 and 29% of the UL for this age group. Therefore, the SCCS considers that the use of zinc in toothpaste per se is safe for children aged 0.5–5 years.Exposure to zinc may also occur from sources other than oral hygiene products. An important source of zinc in the population is the diet. This assessment has not taken into account the daily dietary intake of zinc.The dietary zinc intake (estimated by EFSA in 2014) ranges from 6.8 to 14.5 mg/day in adolescents aged 10 to < 18 years, from 5.5 to 9.3 mg/day in children aged 3 to < 10 years and from 4.6 to 6.2 mg/day in children aged 1 to <3 years. Therefore, exposure to zinc via the diet may already exceed or be close to exceeding the upper limits of 18, 13, 10 and 7 mg/day for the age groups 11–14, 7–10, 3–7 and 1–3 years, respectively. Any additional source of exposure, including cosmetics, may lead to exceeding the upper limits for children.The SCCS cannot advise which portion of the upper limit should be allocated to exposure from cosmetic products. When assessing exposure to chemicals, allocation factors that reflect a reasonable level of exposure while still being protective may be applied. For exposure via toys or drinking water, for example, allocation factors of 10% or 20% of the reference value may be considered as safe. In the case of zinc, the use of 1% in toothpaste and 0.1% in mouthwash constitutes between 10 and 35% of the upper limit depending on the age group. The SCCS is aware that upper limits may be exceeded in some cases because the default values used in this Opinion are based on conservative estimates.

Opinion of the scientific committee on consumer safety (SCCS) – Opinion on the safety of cosmetic ingredient phenylene bis-diphenyltriazine (CAS No 55514-22-2) - S86

Based on the data provided in the dossier, the SCCS considers Phenylene Bis-Diphenyltriazine, S86, safe for use as a UV-filter in sunscreen products at a concentration up to 5%. Because of the insoluble nature of S86 and as no data were provided on safety via inhalation exposure, the SCCS considers its use safe only in dermally applied products and not in products that would lead to inhalation exposure.

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

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.