SummaryExposure to titanium (Ti) from implants and from personal care products as nanoparticles (NPs) is common. This article reviews exposure sources, ion release, skin penetration, allergenic effects, and diagnostic possibilities. We conclude that human exposure to Ti mainly derives from dental and medical implants, personal care products, and foods. Despite being considered to be highly biocompatible relative to other metals, Ti is released in the presence of biological fluids and tissue, especially under certain circumstances, which seem to be more likely with regard to dental implants. Although most of the studies reviewed have important limitations, Ti seems not to penetrate a competent skin barrier, either as pure Ti, alloy, or as Ti oxide NPs. However, there are some indications of Ti penetration through the oral mucosa. We conclude that patch testing with the available Ti preparations for detection of type IV hypersensitivity is currently inadequate for Ti. Although several other methods for contact allergy detection have been suggested, including lymphocyte stimulation tests, none has yet been generally accepted, and the diagnosis of Ti allergy is therefore still based primarily on clinical evaluation. Reports on clinical allergy and adverse events have rarely been published. Whether this is because of unawareness of possible adverse reactions to this specific metal, difficulties in detection methods, or the metal actually being relatively safe to use, is still unresolved.Key words: contact allergy; corrosion; dermatitis; hypersensitivity; lymphocyte transformation test; patch test; penetration; release; titanium; toxicity. Titanium (Ti) is a non-essential metallic element with the atomic number 22 and a silvery colour. It is the ninth most abundant element in the earth's crust and the seventh most abundant metal overall (1). Major deposits of Ti minerals are found in Australia, Canada, India, Norway, South Africa, Ukraine, and the United States. The +4 oxidation state dominates Ti chemistry, but compounds in the +3 oxidation state are also common. TheCorrespondence: Jacob P. Thyssen, National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital HerlevGentofte, University of Copenhagen, Kildegaardsvej, DK-2900 Hellerup, Denmark. Tel: +45 3977 7307; Fax: +45 3977 7118. E-mail: jacob.p. thyssen@regionh.dk Accepted for publication 8 February 2016most important oxide is Ti dioxide (TiO 2 ), which exists in three different crystalline forms -anatase, brookite, and rutile -in addition to an amorphous phase (2, 3). Both the anatase, rutile and brookite mineral forms of TiO 2 occur naturally.TiO 2 is widely applied as microparticles and nanoparticles (NPs) in consumer goods, including cosmetics and foods, to obtain a white colour and ultraviolet light protection (4). Moreover, Ti is combined with a variety of other elements to produce strong lightweight alloys that provide resistance against corrosion and show a very high strength/density ratio (5). Because of this and the...

Given the adjuvant role of costimulatory danger signals, the development of contact allergies to the stimulatory metals may be facilitated by signals from direct TLR4 ligation, whereas other metal sensitizers, such as chromium, may rather depend on microbial or tissue-derived cofactors to induce clinical sensitization.

Background Since periodontitis is bi-directionally associated with several systemic diseases, such as diabetes mellitus and cardiovascular diseases, it is important for medical professionals in a non-dental setting to be able examine their patients for symptoms of periodontitis, and urge them to visit a dentist if necessary. However, they often lack the time, knowledge and resources to do so. We aim to develop and assess “quick and easy” screening tools for periodontitis, based on self-reported oral health (SROH), demographics and/or salivary biomarkers, intended for use by medical professionals in a non-dental setting. Methods Consecutive, new patients from our outpatient clinic were recruited. A SROH questionnaire (8 questions) was conducted, followed by a 30 s oral rinse sampling protocol. A complete clinical periodontal examination provided the golden standard periodontitis classification: no/mild, moderate or severe periodontitis. Total periodontitis was defined as having either moderate or severe. Albumin and matrix metalloproteinase-8 concentrations, and chitinase and protease activities were measured in the oral rinses. Binary logistic regression analyses with backward elimination were used to create prediction models for both total and severe periodontitis. Model 1 included SROH, demographics and biomarkers. The biomarkers were omitted in the analysis for model 2, while model 3 only included the SROH questionnaire. The area under the receiver operating characteristic curves (AUROCC) provided the accuracy of each model. The regression equations were used to create scoring algorithms, composed of the remaining predictors, each with its own weight. Results Of the 156 patients participating in this study, 67% were classified with total periodontitis and 33% had severe periodontitis. The models for total periodontitis achieved an AUROCC of 0.91 for model 1, 0.88 for model 2 and 0.81 for model 3. For severe periodontitis, this was 0.89 for model 1, 0.82 for model 2 and 0.78 for model 3. The algorithm for total periodontitis (model 2), which we consider valid for the Dutch population, was applied to create a freely accessible, web-based screening tool. Conclusions The prediction models for total and severe periodontitis proved to be feasible and accurate, resulting in easily applicable screening tools, intended for a non-dental setting. Electronic supplementary material The online version of this article (10.1186/s12903-019-0784-7) contains supplementary material, which is available to authorized users.

Clinically, it is important for palladium-sensitized patients to undergo an oral examination, with particular attention to the presence of/exposure to dental crowns. In the case of metal contact allergy, exposure to dental crowns could play a role.

Three per cent Na2 PdCl4 pet. is the most suitable patch test concentration. Sensitization to palladium is almost as prevalent as sensitization to nickel. The sex distribution is different between nickel-sensitized and palladium-sensitized patients, suggesting different sources of exposure.

The sensitivity of patch testing with Na(2)[PdCl(4)] is increased compared with the PdCl(2) salt. Therefore, it can be concluded that Na(2)[PdCl(4)] is to be a better test salt for diagnosing palladium allergy with patch testing.

The cytotoxicity of a dental alloy depends on, but is not limited to, the extent of its corrosion behavior. Individual ions may have effects on cell viability that are different from metals interacting within the alloy structure. We aimed to investigate the cytotoxicity of individual metal ions in concentrations similar to those reported to be released from Pd-based dental alloys on mouse fibroblast cells. Metal salts were used to prepare seven solutions (concentration range 100 ppm-1 ppb) of the transition metals, such as Ni(II), Pd(II), Cu(II), and Ag(I), and the metals, such as Ga(III), In(III), and Sn(II). Cytotoxicity on mouse fibroblasts L929 was evaluated using the MTT assay. Ni, Cu, and Ag are cytotoxic at 10 ppm, Pd and Ga at 100 ppm. Sn and In were not able to induce cytotoxicity at the tested concentrations. Transition metals were able to induce cytotoxic effects in concentrations similar to those reported to be released from Pd-based dental alloys. Ni, Cu, and Ag were the most cytotoxic followed by Pd and Ga; Sn and In were not cytotoxic. Cytotoxic reactions might be considered in the etiopathogenesis of clinically observed local adverse reactions.

Recently, a crucial role of Th2 responses in nickel allergic contact dermatitis (ACD) was demonstrated. As palladium allergy is an issue of growing interest, the diagnostic potential of Th2 parameters for palladium sensitization was investigated. Palladium (Na(2) [PdCl(4)])-induced lymphocyte proliferation (LPT), Th1 and Th2 cytokine production were correlated with skin test (ST) reactivity in 16 positive and 21 negative controls. Furthermore, the diagnostic potential of these assays was evaluated using receiver operating characteristics (ROC) analysis. For comparison, same experiments were carried out for nickel (NiSO(4)). Correlation coefficients between palladium ST reactivity and IFN-γ, LPT, IL-5, and IL-13 were 0.34, 0.51, 0.69, and 0.78, and overall test accuracies were 68%, 81%, 89%, and 95%, respectively. Both palladium- and nickel-mediated Th2 responses tightly correlate with ST reactivity, supporting recent findings on the crucial role of Th2 involvement in ACD. Therefore, these assays may have great potential as diagnostic tools for future in vitro sensitization testing.