Distribution and Excretion of BisGMA in Guinea Pigs

Bisphenol-A-glycidyldimethacrylate (BisGMA) is used in many resin-based dental materials. It was shown in vitro that BisGMA was released into the adjacent biophase from such materials during the first days after placement. In this study, the uptake, distribution, and excretion of [14C]BisGMA applied via gastric and intravenous administration (at dose levels well above those encountered in dental care) were examined in vivo in guinea pigs to test the hypothesis that BisGMA reaches cytotoxic levels in mammalian tissues. [14C]BisGMA was taken up rapidly from the stomach and intestine after gastric administration and was widely distributed in the body following administration by each route. Most [14C] was excreted within one day as 14CO2. The peak equivalent BisGMA levels in guinea pig tissues examined were at least 1000-fold less than known toxic levels. The peak urine level in guinea pigs that received well in excess of the body-weightadjusted dose expected in humans was also below known toxic levels. The study therefore did not support the hypothesis

Distribution and Excretion of TEGDMA in Guinea Pigs and Mice

The monomer triethyleneglycoldimethacrylate (TEGDMA) is used as a diluent in many resin-based dental materials. It was previously shown in vitro that TEGDMA was released into the adjacent biophase from such materials during the first days after placement. In this study, the uptake, distribution, and excretion of 14C-TEGDMA applied via gastric, intradermal, and intravenous administration at dose levels well above those encountered in dental care were examined in vivo in guinea pigs and mice as a test of the hypothesis that TEGDMA reaches cytotoxic levels in mammalian tissues. 14C-TEGDMA was taken up rapidly from the stomach and small intestine after gastric administration in both species and was widely distributed in the body following administration by each route. Most 14C was excreted within one day as 14 CO2. The peak equivalent TEGDMA levels in all mouse and guinea pig tissues examined were at least 1000-fold less than known toxic levels. The study therefore did not support the hypothesis

Expression of CYP450-2E1 and formation of 2,3-epoxymethacrylic acid (2,3-EMA) in human oral cells exposed to dental materials.

Objectives. Methacrylate-based (co)monomers released from dental composites can be, metabolized in vivo to methacrylic acid (MA). MA can be further oxidized to the toxic 2,3-epoxymethacrylic acid (2,3-EMA) by cytochrome P450 (CYP450) enzymes. The subform CYP450-2E1, can metabolize xenobiotics with low-molecular weight to epoxides. Oral cells are highly exposed to (co) monomers released from composites. Therefore in this study the, expression of CYP450-2E1 in human oral (and other) cells was investigated as well as the formation of 2,3-EMA in cells exposed to MA. Methods. Following human oral cells were used: human gingiva fibroblasts (HGF), human pulp fibroblasts (HPF), and human tumor buccal keratinocytes (SqCC/Y1). As negative control V79 cells without CYP450-2E1 expression were used. As positive controls V79 cells with CYP450-2E1 expression (V79-CYP450-2E1) and pooled human liver microsomes were used. The expression of CYP450-2E1 in cells was analyzed with the real-time polymerase chain reaction (RT-PCR). 2,3-EMA was quantified by the use of the method of gas chromatography/mass spectrometry (GC/MS). Results. The highest expression of CYP450-2E1 was found in human liver microsomes, followed by SqCC/Y1 cells, V79-CYP450-2E1 cells, HGF, and HPF. The highest amount of 2,3-EMA (mu mol/L; mean +/- SEM, n = 3) was found in human liver microsomes (5.0 +/- 1.0), followed by SqCC/Y1 cells (2.5 +/- 0.8), V79-CYP450-2E1 cells (1.5 +/- 0.6), HPF (0.3 +/- 0.3), and HGF (0.2 +/- 0.2). Significance. It is concluded that the formation of the toxic epoxide 2,3-EMA, as intermediate in the metabolism of dental materials, can occur also in human oral cells which can express the CYP450-2E1 enzyme system

Analysis of titanium and other metals in human jawbones with dental implants - a case series study.

OBJECTIVE: The aim of this study was to measure titanium (Ti) content in human jawbones and to show that Ti was released from dental implants inserted into these jawbones. METHODS: Seven samples from four human subjects with dental implants were analysed as test group and six bone samples of similar topographical regions from six human subjects without implants served as control. The contents of various elements in human jawbones were detected by inductively coupled plasma optical emission spectrometry. The distributions of various isotopes in human mandibular bone were measured with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Histological analyses of undecalcified, Giemsa-Eosin stained mandible sections were performed by light microscopy and particles were identified in human bone marrow by scanning electron microscope-energy dispersive X-ray analysis. RESULTS: In test group only Ti content was significantly higher compared to control group. The mean contents of Ti were 1940μg/kg in test group and 634μg/kg in control group. The highest Ti content detected in human mandibular bone was 37,700μg/kg-bone weight. In samples 4-7 (human subjects II-IV), increased Ti intensity was also detected by LA-ICP-MS in human mandibular tissues at a distance of 556-1587μm from implants, and the intensity increased with decreasing distance from implants. Particles with sizes of 0.5-40μm were found in human jawbone marrow tissues at distances of 60-700μm from implants in samples 4-7. SIGNIFICANCE: Ti released from dental implants can be detected in human mandibular bone and bone marrow tissues, and the distribution of Ti in human bone was related to the distance to the implant

Intracellular uptake and toxicity of three different Titanium particles.

Introduction: Titanium (Ti) and its alloys are used for implants and other dental materials. In this study, cytotoxicity, DNA damage, cellular uptake and size of three kinds of Ti particles were measured. Methods: Cytotoxicity for Ti microparticles (Ti-MPs, <44. μm), NiTi microparticles (NiTi-MPs, <44. μm), and Ti nanoparticles (Ti-NPs, <100. nm) in periodontal ligament (PDL)-hTERT cells was measured with XTT test. DNA damage was determined with comet assay. Particle size was measured with scanning electron microscope, intracellular uptake was determined with laser scanning confocal microscopy and transmission electron microscopy. Results: The EC50 values of investigated particles were: 2.8mg/ml (Ti-NPs), 41.8mg/ml (NiTi-MPs) and >999mg/ml (Ti-MPs). The Olive Tail Moment (OTM) values at 1/10 EC50 were: 3.2 (Ti-NPs) and 2.2 (NiTi-MPs). An OTM of 2.2 for Ti-MPs was detected at the concentration of 6666μg/ml. Determined sizes of investigated particles were 20-250nm (Ti-NPs), 0.7-90μm (NiTi-MPs) and 0.3-43μm (Ti-MPs). The highest cellular uptake efficiency was observed with Ti-NPs, followed by Ti-MPs and NiTi-MPs. Only Ti-NPs were found in the nucleus. Conclusion: Compared to Ti-MPs and NiTi-MPs, Ti-NPs induced higher cellular uptake efficiency and higher toxic potential in PDL-hTERT cells. Ni in the alloy NiTi induced an increase in the toxic potential compared to Ti-MPs

Titanium and zirconium release from titanium- and zirconia implants in mini pig maxillae and their toxicity in vitro.

OBJECTIVE: Titanium (Ti)- and Zirconia (ZrO2)-implants in mini pig maxillae were compared with respect to Ti/zirconium (Zr) release into the surrounding bone tissues, the resulting short term tissue responses and the potential toxicity. METHODS: Ti/Zr release from Ti- and ZrO2-implants in mini pig maxillae was determined with inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). The spatial distribution of Ti and Zr in maxilla tissues near the implant surface was assessed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). A histological analysis was performed to investigate the tissue responses after 12 weeks of implantation. The cytotoxicity and DNA damage of Ti particles and ZrO2 particles were studied with XTT and Comet assay. RESULTS: The mean Ti content in the bone adjacent to Ti-implants was 1.67 mg/kg-bone weight. The highest Ti content detected was 2.17 mg/kg-bone weight. The mean Zr content in the bone adjected to ZrO2-implants was 0.59 mg/kg-bone weight. The highest Zr content was 0.75 mg/kg-bone weight. The spatial distribution of the Ti and Zr in bone showed mainly a higher intensity of Ti and Zr close to the screw thread outer tip rather. Histological analysis indicated that near both implant-types signs of bone marrow fibrosis were present. EC50 of commercially available ZrO2-nanoparticles (NPs, <100 nm) and ZrO2-microparticles (MPs, <5 μm) was 13.96 mg/ml and 80.99 mg/ml, respectively. ZrO2-NPs and ZrO2-MPs can induce DNA damage at 70 μg/ml and 810 μg/ml, respectively. SIGNIFICANCE: After 12-weeks of implantation, increased concentrations of Ti and Zr can be detected in bone/tissues near Ti- and ZrO2-implants in mini pig maxillae. Ti content released from Ti-implants is two times higher than the Zr content released from ZrO2-implants. ZrO2-NPs showed lower cytotoxicity and DNA damage compared to results reported for Ti-NPs in human cells