Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories: The Aragon Workers Health Study.

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

Quantification of titanium dioxide nanoparticles in human urine by single-particle ICP-MS.

The increasing use of titanium dioxide nanoparticles in daily use consumer products such as cosmetics, personal care products, food additives, and even medicine has led to growing concerns regarding human safety. It would be ideal to track exposure to this emerging nanopollutant, for example through bioassays, however, so far nanoparticle assessment in biological matrices such as urine remains challenging. The lack of data is mainly due to the limitations of the current metrology, but also to the low expected concentration in human samples. In this study, a quantification method for titanium dioxide nanoparticles in urine has been developed and validated following the ISO/CEI 17025:2017 guidelines. The detection limit for titanium dioxide nanoparticle mass concentration by single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) was 0.05 ng mL-1. The particle size limit was determined using three different approaches, with the highest calculated limit value approaching 50 nm. Repeatability and reproducibility of 14% and 18% respectively were achieved for particle mass concentration, and 6% for both parameters for particle size determination. Method trueness and recovery were 98% and 84%, respectively.

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant.

Titanium dioxide is produced or imported into the EU for over one million tons/year. The International Agency for Research on Cancer (IARC) classification is 2B, a possible inhalation carcinogen for humans. This study evaluates urinary biomarkers of oxidative stress in workers of a plant producing TiO2 pigment powder, having 0.25 µm average particle size and an ultrafine fraction, compared to unexposed subjects. Urine samples were collected from forty workers before and after the shift, from six employees of the same company and eighteen volunteers from the same geographical area. Titanium and other metals concentrations were measured by ICP-MS, while DNA, RNA, and protein oxidation products by HPLC/MS-MS. A statistically significant increase was found for the urinary concentration of Al, Cd, Cr, Cu, Fe, Mn, Pb, Ti, and Zr, and for all biomarkers of oxidative stress in post-shift workers' urine samples. Urinary concentrations after the working shift were higher than for employees and volunteers pooled together for Cd, Mn, and Zr, and for the oxidative stress biomarkers 8-oxoGuo, 8-oxodGuo, and 3NO2Tyr. Biomonitoring studies on dose and effect biomarkers for TiO2 occupational exposure provide information useful for protecting workers' health even in conditions that comply with health and safety standards, highlighting reversible effects of chronic exposure at very low doses.

Evaluation of the release of nickel and titanium under orthodontic treatment.

The metal alloys used in dentistry are made mainly of nickel (Ni), titanium (Ti), and other elements such as molybdenum (Mo), zirconium (Zr), iron (Fe), tin (Sn), chrome (Cr), carbon (C), copper (Cu) and niobium (Nb) which can release metal ions in unstable environments. The aim of this work was determine the salivary pH before and during orthodontic treatment; evaluate the release of metal ions, mainly Ni and Ti, in urine and saliva using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES); and evaluate the corrosion using Scanning Electronic Microscopy (SEM). In this study, we selected 35 individuals under orthodontic treatment, from whom saliva and urine samples were collected in 3 stages: (a) basal, (b) at 3 and (c) 6 months after the placement of the fixed appliances. SEM analyzed the Ni-Ti (0.016″) and stainless steel (SS) (0.016 × 0.022″) archs after 1 month of being in contact with the oral cavity. Statistical analysis was performed with Stata using the ANOVA model of repeated measures with a p < 0.05. A statistically significant difference in the concentration of Ni in saliva were found between 3 and 6 months of intervention and Ti in urine was found 3 and 6 months.

Possibilities of single particle-ICP-MS for determining/characterizing titanium dioxide and silver nanoparticles in human urine.

OBJECTIVE: The current use of nanoparticles in personal care and cosmetics, food safety, agriculture, medicine and pharmacy has led to a growing concern on the toxicity of these emerging materials to humans and also to the environment. Nanoparticles assessment (determination and size distribution) is a challenge mainly due to limitations of the current analytical instrumentation, but also because nanoparticles in foodstuff and environmental samples are usually found at low concentrations. The scenario is even more critical when dealing with clinical samples, mainly when trying to assess nanoparticles at basal levels in complex samples such as blood and urine. The aim of this paper is to find data regarding the presence of nanoparticles at basal levels in urine human samples. METHODS: The use of single particle - inductively couple plasma - mass spectrometry (sp-ICP-MS) has been explored to determine and characterize silver and titanium dioxide nanoparticles in human urine. Urine samples were directly diluted (1:5 to 1:10) with 1%(v/v) glycerol before sp-ICP-MS measurements, and efforts were made for validating the over-all procedure. RESULTS: The limit of detection and quantification for Ag NPs were 5.72 × 103 and 1.91 × 104 Ag NPs mL-1, respectively; whereas, values for TiO2 NP concentrations were 4.31 × 103 and 1.44 × 104 TiO2 NPs mL-1. The limit of detection in size after applying several methods (3σ/5σ criteria) was found to be within the 8-9 nm for Ag NPs, and from 15 to 18 nm for TiO2 NPs. Within-batch precision for Ag NP concentration was 15% (11% for mean size of nanoparticle distributions). Repeatability for TiO2 NPs was 25% (TiO2 NP concentration) and 9% (TiO2 NP mean size). Good analytical recovery rates were found for spiked experiments with Ag NP standards of 40 and 60 nm (values within the 104-106% range), and also for TiO2 NPs of 50 and 100 nm (96-98%). Finally, basal levels of Ag NPs and TiO2 NPs, as well as total Ag and Ti concentrations, in human urine were assessed. Low Ag and Ag NP concentrations were found. Ag NPs exhibited mean sizes of approximately 16-17 nm. Total Ti levels, however, were higher than total Ag concentration, and TiO2 NP concentrations within the 1.56 × 104-2.80 × 104 NPs mL-1 range were measured (TiO2 NP mean sizes were from 76 to 98 nm).

Absorption, Distribution and Excretion of Four Forms of Titanium Dioxide Pigment in the Rat.

Titanium dioxide (TiO2 ) is a white color additive that has a long history of global approval and use in food. There is, however, considerable confusion regarding the applicability of the biological effects of novel, engineered, nano-sized forms of TiO2 developed for nonpigmentary applications to the safety of oral exposure to food grade TiO2 pigment. The objective of this study was to assess the absorption, distribution, and routes of excretion in rats after oral exposure to food grade TiO2 . Four different grades of TiO2 (200 ppm) or control (0 ppm) diets were fed to rats for 7 consecutive days, followed by control diet only for 1, 24, or 72 h. Concentrations of titanium in liver, kidney and muscle were mainly below the limit of detection (<0.1 to < 0.2 mg/kg wet weight); tissue concentrations of titanium above the LOD were in the range of 0.1 to 0.3 mg/kg wet weight for all groups. Whole blood concentrations of titanium were <0.04 mg/L for all groups. Urinary excretion of titanium was equivalent to <2% daily dose/L of urine for all groups and was generally below the limit of quantification (<0.04 mg/L). Feces represented the predominant route of excretion. These results demonstrate that there is no accumulation of titanium in tissues following consumption of diets containing 200 ppm food grade TiO2 . No differences in systemic absorption of the 4 forms of TiO2 were observed indicating that the bioavailability of TiO2 is consistently low for the range of particle sizes and morphologies examined in this study.

Quantitative biokinetics of titanium dioxide nanoparticles after intravenous injection in rats: Part 1.

Submicrometer TiO2 particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also drug delivery applications are envisaged. Beyond exposure of occupational groups, this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs are poorly understood and in many investigations excessive doses are applied. The present study investigates the biokinetics and clearance of a low single dose (typically 40-400 µg/kg BW) of 48V-radiolabeled, pure TiO2 anatase nanoparticles ([48V]TiO2NP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous (IV) injection into female Wistar rats. Biokinetics and clearance were followed from one-hour to 4-weeks. The use of radiolabeled nanoparticles allowed a quantitative [48V]TiO2NP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chemical background levels possibly caused by dietary or environmental titanium exposure. Highest [48V]TiO2NP accumulations were found in liver (95.5%ID after one day), followed by spleen (2.5%), carcass (1%), skeleton (0.7%) and blood (0.4%). Detectable nanoparticle levels were found in all other organs. The [48V]TiO2NP content in blood decreased rapidly after 24 h while the distribution in other organs and tissues remained rather constant until day-28. The present biokinetics study is part 1 of a series of studies comparing biokinetics after three classical routes of intake (IV injection (part 1), ingestion (part 2), intratracheal instillation (part 3)) under identical laboratory conditions, in order to test the common hypothesis that IV-injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes. This hypothesis is disproved by this series of studies.

Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2.

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48V-radiolabeled [48V]TiO2 nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [48V]TiO2-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [48V]TiO2-nanoparticle doses in the range of 30-80 µg•kg-1 bodyweight, making use of the high sensitivity of the radiotracer technique. The [48V]TiO2-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for 48V-ions not bound to TiO2-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiable [48V]TiO2-nanoparticle organ concentrations present in liver (0.09 ng•g-1), lungs (0.10 ng•g-1), kidneys (0.29 ng•g-1), brain (0.36 ng•g-1), spleen (0.45 ng•g-1), uterus (0.55 ng•g-1) and skeleton (0.98 ng•g-1). Since chronic, oral uptake of TiO2 particles (including a nano-fraction) by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large. After normalizing the fractions of retained [48V]TiO2-nanoparticles to the fraction that passed the gastro-intestinal-barrier and reached systemic circulation, the biokinetics was compared to the biokinetics determined after IV-injection (Part 1). Since the biokinetics patterns differ largely, IV-injection is not an adequate surrogate for assessing the biokinetics after oral exposure to TiO2 nanoparticles.

Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3.

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48V-radiolabeled [48V]TiO2 nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1 h, 4 h, 24 h, 7 d and 28 d after intratracheal instillation of a single dose of an aqueous [48V]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [48V]TiO2-nanoparticle doses in the range of 40-240 µg·kg-1 bodyweight and making use of the high sensitivity of the radiotracer technique. The [48V]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for 48V-ions not bound to TiO2-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1 h and were retained mainly in the carcass (4%); 0.3% after 28 d. Highest organ fractions of [48V]TiO2-nanoparticles present in liver and kidneys remained constant (0.03%). [48V]TiO2-nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5 to 20% of all translocated/absorbed [48V]TiO2-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [48V]TiO2-nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part 1) and gavage (GAV) (Part 2). The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications. Considering that chronic occupational inhalation of relatively biopersistent TiO2-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.

[Evaluation of health effect among occupational population exposed to nano-titanium dioxide: a cross-sectional study].

Objective: To characterize the health effects of nano-titanium dioxide exposure in an occupational cohort. Methods: Eighty-five male employees of a nano-titanium dioxide manufacturing enterprise in Shandong Province were evaluated in September 2014. Forty-four were exposed to nano-titanium dioxide (exposure group), and 41 were not exposed to nano-titanium dioxide (control group). We collected employees' basic information, smoking and drinking history, previous medical history, family history, and occupational history. Differences in blood pressure, hematological parameters, and blood biochemistry between the two groups were analyzed and compared. Multiple linear regression analysis was used to investigate the effect of nano-titanium dioxide exposure on blood pressure, hematological parameters, and blood biochemistry indices after controlling for age, smoking, drinking, and body mass index (BMI). Twenty-five employees from the exposure group and 25 employees from the control group were selected at random for measurement of genetic damage by cytokinesis-block micronucleus assay. Poisson regression analysis was used to investigate the effect of nano-titanium dioxide exposure on micronucleus frequency or micronucleus cell frequency after controlling for age, smoking, drinking, and BMI. Results: The median (P25-P75) surface area concentration of particles deposited in the tracheobronchial region, the surface area concentration of particles deposited in the alveolar region, and particle number concentration in the exposure group were 35.35(24.31-57.42) µ m2/cm3, 173.09(116.27-270.72) µ m2/cm3, and 40 244.00 (17 803.50-78 679.00) /cm3, respectively. These values were significantly higher than those in the control group 33.90 (27.44-43.29) µm2/cm3, 150.50(125.82-192.87)µm2/cm3, and 18 721.00 (12 721.00-51 898.50)/cm3, respectively. Z values were 15.47, 15.96, and 14.54, respectively (P<0.001 for all three values). Multiple linear regression analysis showed that exposure to nano-titanium dioxide contributed most to the alteration of mean corpuscular hemoglobin concentration, creatinine, and LDL-C, with standardized regression coefficients of 0.23, -0.51, and 0.30, respectively (P<0.05 for all three values), after adjusting for age, smoking, drinking, and BMI. There were no significant differences in micronucleus frequency and micronucleus cell frequency between the exposure group (3.00‰ (1.50‰-5.00‰) and 3.00‰ (2.00‰-4.00‰), respectively) and control group (2.00‰ (1.00‰-4.50‰) and 2.00‰ (1.00‰-4.00‰), respectively); P>0.05 for all comparisons. Poisson regression analysis showed that after adjusting for age, smoking, drinking, and BMI, there was still no statistically significant correlation between nano-titanium dioxide exposure and micronucleus frequency (OR=1.11, 95% CI: 0.81-1.54) or micronucleus cell frequency (OR=1.07, 95% CI: 0.75-1.51); P>0.05 for all comparisons. Conclusion: Nano-titanium dioxide particles exerted some health effects on the occupationally-exposed cohort, whose hematological parameters and blood biochemistry were influenced to some degree. However, a potential link between occupational exposure to nano-titanium dioxide and blood pressure or induction of genetic damage or was not found.

Raman microspectroscopy of exhaled breath condensate and urine in workers exposed to fine and nano TiO2 particles: a cross-sectional study.

The health effects of engineered nanoparticles in humans are not well-understood; however experimental data support the theory of oxidative stress promoting fibrogenesis and carcinogenicity. The aim of this study was to detect TiO2 particles in exhaled breath condensate (EBC) and urine samples to ascertain their presence and potential persistence and excretion in urine.EBC and urine samples were collected from 20 workers exposed to TiO2 aerosol; among them, 16 had a higher risk level of exposure (production workers) and four had medium risk level (research workers); in addition to 20 controls. Titanium levels in EBC and urine were analysed using the inductively coupled plasma mass spectrometry (ICP-MS) method. A Raman microspectroscopic analysis was performed in EBC and urine to identify the phase composition of TiO2 particles observed. Aerosol exposure in the workplaces was measured using SMPS and APS spectrometers and P-TRAK and DustTRAK DRX monitors.The median concentration of TiO2 aerosol was 1.98 × 10(4) particles cm(-3), the interquartile range (IQR) was 1.50 × 10(4) - 3.01 × 10(4) particles cm(-3) and the median mass concentration was 0.65 mg m(-3) (IQR 0.46-.0.83 mg m(-3)); 70-82% of the particles were smaller than 100 nm in diameter. In any part of the plant, the median TiO2 air concentration did not exceed the national airborne exposure limit of 10 mg m(-3) for inert dust. Particles of rutile and/or anatase were found in the EBC of exposed workers in 8/20 (40%) of the pre-shift and 14/20 (70%) of the post-shift samples. In the urine of workers, TiO2 particles were detected in 2/20 post-shift urine samples only. The mean concentration of titanium in the EBC in production workers was 24.1 ± 1.8 µg/l. In the research workers the values were below the limit of quantitation; LOQ = 4.0 ± 0.2 µg/l), as well as in the controls. In the urine samples of all of the subjects, titanium was under the limit of detection (LOD = 1.2 µg/l). Raman microanalysis of EBC in the workers confirmed the presence of TiO2 anatase and/or rutile crystal phases in the pre-shift samples and their persistence from previous shifts in the workers.

Metal release and metal allergy after total hip replacement with resurfacing versus conventional hybrid prosthesis.

BACKGROUND: Metal-on-metal (MOM) total hip arthroplasties were reintroduced because of the problems with osteolysis and aseptic loosening related to polyethylene wear of early metal-on-polyethylene (MOP) arthroplasties. The volumetric wear rate has been greatly reduced with MOM arthroplasties; however, because of nano-size wear particles, the absolute number has been greatly increased. Thus, a source of metal ion exposure with the potential to sensitize patients is present. We hypothesized that higher amounts of wear particles result in increased release of metal ions and ultimately lead to an increased incidence of metal allergy. METHODS: 52 hips in 52 patients (median age 60 (51-64) years, 30 women) were randomized to either a MOM hip resurfacing system (ReCap) or a standard MOP total hip arthoplasty (Mallory Head/Exeter). Spot urine samples were collected preoperatively, postoperatively, after 3 months, and after 1, 2, and 5 years and tested with inductively coupled plasma-sector field mass spectrometry. After 5 years, hypersensitivity to metals was evaluated by patch testing and lymphocyte transformation assay. In addition, the patients answered a questionnaire about hypersensitivity. RESULTS: A statistically significant 10- to 20-fold increase in urinary levels of cobalt and chromium was observed throughout the entire follow-up in the MOM group. The prevalence of metal allergy was similar between groups. INTERPRETATION: While we observed significantly increased levels of metal ions in the urine during the entire follow-up period, no difference in prevalence of metal allergy was observed in the MOM group. However, the effect of long-term metal exposure remains uncertain.

Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration.

BACKGROUND: The in vivo kinetics of nanoparticles is an essential to understand the hazard of nanoparticles. Here, the absorption, distribution, and excretion patterns of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles following oral administration were evaluated. METHODS: Nanoparticles were orally administered to rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti or Zn in each sample was measured using inductively coupled plasma-mass spectrometry. RESULTS: TiO2 nanoparticles had extremely low absorption, while ZnO nanoparticles had higher absorption and a clear dose-response curve. Tissue distribution data showed that TiO2 nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the liver and kidney were significantly increased compared with the vehicle control. ZnO nanoparticles in the spleen and brain were minimally increased. Ti concentrations were not significantly increased in the urine, while Zn levels were significantly increased in the urine, again with a clear dose-response curve. Very high concentrations of Ti were detected in the feces, while much less Zn was detected in the feces. CONCLUSIONS: Compared with TiO2 nanoparticles, ZnO nanoparticles demonstrated higher absorption and more extensive organ distribution when administered orally. The higher absorption of ZnO than TiO2 nanoparticles might be due to the higher dissolution rate in acidic gastric fluid, although more thorough studies are needed.

Urinary titanium and vanadium and breast cancer: a case-control study.

Titanium and vanadium are essential trace elements. This study examined the associations of urinary titanium and vanadium with breast cancer risk in a hospital-based case-control study comprising 240 women with incident breast cancer, and 246 cancer-free and age-matched controls who attended health screening assessments in 2 affiliated hospitals of Sun Yat-sen University in Guangzhou between October 2009 and July 2010. Survey data and urine specimens were collected before treatment for the patients and after interview for the controls. The urinary concentrations of titanium and vanadium were measured by inductively coupled plasma mass spectrometry. Women in the second and the highest tertile of vanadium showed 64% and 40% decreased risk of breast cancer, respectively, when compared with those in the lowest tertile after adjustment for established risk factors of breast cancer (ORs [95%CI]: 0.36 [0.21-0.60] and 0.60 [0.37-0.97], respectively). In contrast, urinary titanium was not significantly related to a decreased risk of breast cancer. These results have potentially significant implications on nutritional chemoprevention of breast cancer and the development of new anticancer drugs. Further replications of the study are recommended, and the biological mechanisms warrant clarification.

[The effect of inhalable titanium dioxide on the oxidative stress among occupational population].

OBJECTIVE: To investigate the inhalable titanium dioxide exposure level and make an assessment of its oxidative effect on occupational exposed population. METHODS: A total of 7 workers occupationally exposing to inhalable titanium dioxide were recruited into the study. The basic information and occupational history were collected by interview, while their blood sample (10 ml for each subject) were collected before and after the investigation, respectively. Pre- and post-work shift urine samples (60 ml for each subject) were collected for 29 days consecutively. The daily personal titanium dioxide exposure level, temperature and relative humidity were detected too. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP) were detected by ELISA and latex immunoturbidimetric assay, respectively. RESULTS: The mean concentration of air inhalable titanium dioxide was (1.194 ± 1.015) mg/m(3). Serum hs-CRP level before and after the investigation was (1.13 ± 1.08), (1.33 ± 1.01) mg/L, respectively. No statistical significance was observed between hs-CRP level before and after the investigation (t = -0.848, P = 0.425). Pre- and post-work shift urinary 8-OHdG was (3.51 ± 1.39), (3.65 ± 1.06) µmol/mol Cr, respectively. A positive correlation was found between the concentration of inhalable titanium dioxide and the changes of 8-OHdG level (r = 0.192, t = 2.09, P = 0.039). Linear mixed-effect models, adjusted by work shift, years of employment, age, body mass index, smoking status, temperature and relative humidity, showed no significant exposure-respond trend between the inhalable titanium dioxide concentration and 8-OHdG level (ß = 0.288, t = 1.940, P = 0.055). CONCLUSION: Our findings do not support the potential link between occupationally exposure to inhalable titanium dioxide and high induction of DNA oxidative stress.

2008 John Charnley award: metal ion levels after metal-on-metal total hip arthroplasty: a randomized trial.

UNLABELLED: Metal-on-metal bearing total hip arthroplasty is performed more commonly than in the past. There may be manufacturing differences such as clearance, roughness, metallurgy, and head size that affect performance. In a prospective, randomized trial, we compared 2-year postoperative ion levels for a 28-mm metal-on-polyethylene bearing with 28-mm and 36-mm metal-on-metal bearings. We measured serum, erythrocyte, and urine ion levels. We observed no difference in the ion levels for the 28-mm and 36-mm metal-on-metal bearings. The ion levels in these patients were lower than reported for most other metal-on-metal bearings. Although both erythrocyte and serum cobalt increased, erythrocyte chromium and erythrocyte titanium did not increase despite a four- to sixfold serum chromium and a three- to fourfold serum titanium increase. This may represent a threshold level for serum chromium and serum titanium below which erythrocytes are not affected. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

High-resolution ICP-MS determination of Ti, V, Cr, Co, Ni, and Mo in human blood and urine of patients implanted with a hip or knee prosthesis.

The main components (Ti, V, Cr, Co, Ni, and Mo) of metallic alloys currently used in hip and knee articular prostheses have been simultaneously determined in human whole blood and urine of implanted people by a (HR)-ICP-MS method previously developed in our laboratory. The determination of those elements has been carried out in patients with knee and hip prosthesis and in a group of pre-operation patients without any metallic device in their bodies, used as controls, demonstrating the usefulness of this technique to perform multielement analysis at ppt levels in complex matrices. The concentrations of V, Cr, Co, Ni, and Mo in urine and blood of implanted people turned out to be very similar to those obtained in control patients. However, raised Ti levels could be found both in urine and blood of patients with articular prostheses made or coated with a titanium alloy (Ti(6)Al(4)V).

Urinary and serum titanium: assessment as an indicator of exposure to ammonium citratoperoxotitanate (IV) and its influence on renal function.

Ammonium citratoperoxotitanate IV (TAS-FINE) is a water-soluble titanium complex used to synthesize a photocatalytic titanium(IV) oxide film. This study was aimed to investigate the LD50, dose-response, time-course response, and renal toxicity of TAS-FINE using an animal model. Serum titanium (S-Ti) and its 24-h urinary excretion (U-Ti) were determined by inductively coupled plasma-argon emission spectrometry (ICPAES) after a single oral TAS-FINE administration to male Wistar rats. The LD50 of TAS-FINE was 7.97 g/kg body weight in 24 h, and its half-life was 3.78+/-1.28 d for S-Ti and 2.19+/-0.09 d for U-Ti. Although TAS-FINE was not easily absorbed in the gastrointestinal tract, it was distributed into the bloodstream in a dose-dependent manner. Within 24 h, 0.189% of administrated Ti was excreted via urine. It was speculated that TAS-FINE formed conjugates with serum constituents that resulted in nephrotoxicity resulting from an allergic reaction. The observed indices in this study were revealed to be good indicators for TAS-FINE exposure. The analytical method and animal model described in this study will help to further elucidate details about human exposure to TAS-FINE, which in recent times has become an occupational and environmental toxicant of concern.

[Determination of the contents of fourteen elements in urine of Xinjiang kuitun fluorine poisoning and arsenic-fluoride poisoning patients by ICP-AES].

A method of determining the contents of K, Na, Ca, Mg, P, Zn, Al, Ba, Co, Cu, Ni, Sr, Cr and Ti, fourteen elements, in urine of Xinjiang Kuitun fluorine poisoning and arsenic-fluoride poisoning patients was developed. The operation conditions of ICP-AES, and the lowest test concentration, precision and linear ranges were studied. The relative standard deviation of the method was 0.24%-2.47% (n=10), the average recoveries were 90.4%-00.5%. The contents of K and Na in urine of fluorine poisoning and arsenic-fluoride poisoning patients were higher than those of healthy contrast group. The contents of Ba, Co, Cu, Ni and Cr in the urine of arsenic-fluoride poisoning patients were higher than those of fluorine poisoning patients and healthy contrast group (P < 0.05). The contents of P, Ca, Mg, Zn, Al, Sr and Ti do not have statistic significance (P > 0.05). The method was sensitive, simple and accurate. The experiment data was reliable.

Metal ion levels after metal-on-metal proximal femoral replacements: a 30-year follow-up.

Metal-on-metal hip bearings are being implanted into younger patients. The consequence of elevated levels of potentially carcinogenic metal ions is therefore a cause for concern. We have determined the levels of cobalt (Co), chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of patients who had had metal-on-metal and metal-on-polyethylene articulations in situ for more than 30 years. We compared these with each other and with the levels for a control group of subjects. We found significantly elevated levels of whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and urine levels of Co were grossly elevated, by a factor of 50 and 300 times respectively in patients with loose metal-on-metal articulations when compared with the control group. Stable metal-on-metal articulations showed much lower levels. Elevated levels of whole blood or urinary Co may be useful in identifying metal-on-metal articulations which are loose.