Metal concentrations in the blood and tissues after implantation of titanium growth guidance sliding instrumentation.

BACKGROUND: Growth guidance sliding treatment devices, such as Shilla (Medtronic, Minneapolis, MN USA) or LSZ-4D (CONMET, Moscow, Russia), used for the treatment of scoliosis in children who have high growth potential have unlocked fixtures that allow rods to slide during growth of the spine, which avoids periodical extensions. However, the probability of clinical complications associated with metallosis after implantation of such devices is poorly understood. The content of metal ions in the blood and tissues of pediatric patients treated for scoliosis using fusionless growth guidance sliding instrumentation has not yet been investigated. PURPOSE: The aim of the present study was to measure the content of metal ions in the blood and tissues surrounding the implanted growth guidance sliding LSZ-4D devices made of titanium alloy (Ti6Al4V), and to identify the incidence of metallosis-associated clinical complications in some patients with these devices. STUDY DESIGN: This is a one-center, case-control retrospective study. PATIENTS SAMPLE: The study group included 25 patients with high growth potential (22 females, 3 males; average age at primary surgery for scoliosis treatment is 11.4±1.2 years old) who had sliding growth guidance instrumentation LSZ-4D (CONMET) implanted on 13 (range: 10-16) spine levels for 6±2 years. The LSZ-4D device was made from titanium alloy Ti6Al4V and consisted of two rectangular section rods and fixture elements. Locked fixtures were used on one spinal level, whereas the others were unlocked (sliding). The control group consisted of 13 patients (12 females and 1 male; 11±1.2 years old) without any implanted devices. OUTCOME MEASURES: The content of Ti, Al, and V metal ions in the whole blood and tissues around the implanted device was measured. The incidences of metallosis-associated complications in the study group were recorded. METHODS: Metal ion content was measured by the inductively coupled mass spectrometry method on quadrupolar NexION 300D (PerkinElmer Inc, Shelton, CT, USA). RESULTS: Five of 25 patients in the study group developed metallosis-associated complications (two sinuses and three seroma in the lumbar part of the spine). Revisions were carried out in two of these patients. Ninety percent of the patients in the study group had increased content of Ti and V ions in the blood (2.8 and 4 times, respectively). Median content of Ti ions in soft tissues adjacentto implanted sliding device was more than 1,500-fold higher than that of the control group. These levels are much higher than previously reported for spinal instrumentation. CONCLUSIONS: Increased content of Ti and V ions in the blood and especially in tissues around the titanium growth guidance sliding device LSZ-4D accompanied by clinical manifestations (seroma and sinuses) indicates the importance of improving wear resistance of such instrumentation with the coatings and the necessity to exchange sliding instrumentation once the child is fully grown.

Acute inhalation exposure to titanium ethanolate as a possible cause of metal fume fever.

Occupational inhalation exposure to noxious agents is not uncommon. Herein, we present a 26-year-old male student who had accidental acute inhalation exposure to a large quantity of titanium ethanolate and hydrogen chloride in chemistry lab. He was referred to the emergency department of our hospital with low-grade fever, dyspnea, headache, fatigue and myalgia. After 24 hrs of symptomatic treatment (oxygen therapy and acetaminophen), the fever was subsided and the patient discharged home in a good clinical condition. The presented symptoms could be interpreted as a form of metal fume fever. It can therefore be concluded that organo-metallic compound of titanium metal may have the potential to produce metal fume fever in human.

How to measure hazards/risks following exposures to nanoscale or pigment-grade titanium dioxide particles.

Due to its multifunctional applications, titanium dioxide particles have widespread use in commerce. The particle-types function as sources of pigment color, in food products, anti-bacterial components, ultraviolet radiation scavengers, catalysts, as well as in cosmetics. Because of its inherent properties in a diverse number of products, exposures may occur via any of the major point-of-entry routes, i.e., inhalation, oral or dermal. Although the majority of TiO2 applications are known to exist in the pigment-grade form, nanoscale forms of TiO2 are also common components in several products. This brief review is designed to identify relevant toxicology and risk-related issues which inform health effects assessments on the various forms of titanium dioxide particles. While there has been an abundance of hazard data generated on titanium dioxide particulates, many of the published reports have limited informational value for assessing health effects due, in large part, to shortcomings in experimental design issues, such as: (1) inadequate material characterization of test samples; (2) questionable relevance of experimental systems employed to simulate human exposures; (3) applications of generally high doses, exclusive focus on acute toxicity endpoints, and a lack of reference benchmark control materials, to afford interpretation of measured results; and/or (4) failure to recognize fundamental differences between hazard and risk concepts. Accordingly, a number of important toxicology issues are identified and integrated herein to provide a more comprehensive assessment of the health risks of different forms of pigment-grade and nanoscale titanium dioxide particles. It is important to note that particle-types of different TiO2 compositions may have variable toxicity potencies, depending upon crystal structure, particle size, particle surface characteristics and surface coatings. In order to develop a more robust health risk evaluation of TiO2 particle exposures, this review focuses on the following issues: (1) Introduction to TiO2 particle chemistry/functionality and importance of robust material characterization of test samples; (2) Implementation of meaningful hazard studies for gauging EHS safety issues ­ pulmonary bioassay data and development of the Nano Risk Framework for developmental nano TiO2 compounds; (3) Epidemiological study findings on titanium dioxide workers ­ the most heavily-exposed populations; (4) Methodologies for setting occupational exposure limits including benchmarking or bridging comparisons; and (5) The importance of particle overload data in the lungs of rats as it relates to gauging the relevance of health effects for humans. A comprehensive evaluation of the existing animal and human health data is a necessary prerequisite for facilitating accurate assessments of human health risks to TiO2 exposures.

Acute group poisoning by titanium dioxide: inhalation exposure may cause metal fume fever.

A large quantity of white gas containing titanium dioxide and hydrogen chloride was generated unexpectedly during an experiment in a chemical laboratory. Fourteen students and staff complained of nausea, dyspnea, or respiratory irritation immediately after inhaling the gas. On arrival at Saint Luke's International Hospital, more than half of the patients presented with low-grade fever. Symptoms spontaneously resolved soon after admission, although the low-grade fever persisted until the following morning. Low-grade fever after inhalation exposure is not explicable by hydrogen chloride inhalation and therefore appeared to be caused by titanium dioxide inhalation, manifesting as metal fume fever. Titanium dioxide is thought to have no remarkable human toxicity and is considered to be safe clinically. To our knowledge, this is the first report of titanium dioxide inhalation as the potential cause of metal fume fever in humans. Correlations between the degree of fever and quantity and concentration of inhaled titanium dioxide remain to be determined.

Photooxidation of a mustard gas simulant over TiO2-SiO2 mixed-oxide photocatalyst: site poisoning by oxidation products and reactivation.

The photooxidation of 2-chloroethyl ethyl sulfide (2-CEES), a simulant for mustard gas, was studied using transmission IR spectroscopy on a mixed-oxide TiO2-SiO2 photocatalyst. Ultraviolet irradiation in the photon energy range from 2.1 to 5 eV was employed at a catalyst temperature of 200 K. Rapid photooxidation was observed by the loss of infrared intensity in the v(CHx) stretching region, and concomitant infrared features of adsorbed oxidation products were observed to develop. The oxidation products, captured on the photocatalyst at 200 K, were found to block 2-CEES readsorption. Upon heating the poisoned photocatalyst to about 300 K, infrared measurements indicate that the adsorbed CO2 oxidation product was desorbed. The capability for full readsorption of 2-CEES was achieved upon heating the poisoned photocatalyst to 397 K, and continued rapid photooxidation of the 2-CEES was then possible at about 1/3 the rate found for the fresh catalyst. Thus thermal treatment at 397 K of oxidation-product-poisoned TiO2-SiO2 material is able to partially restore the TiO2-SiO2 photooxidation activity.

Titanium particles identified by energy-dispersive X-ray microanalysis within the lungs of a painter at autopsy.

A 72-year-old male painter, who complained of his "lungs burning" for 2 weeks, died suddenly. Autopsy examination revealed severe coronary atherosclerosis with plaque rupture as the cause of death. Examination of the lungs revealed emphysema, interstitial fibrosis, and multinucleated giant cells with intra- and extracellular brown-black, crystalline, polarizable foreign material. Energy-dispersive X-ray microanalysis showed the material to contain titanium, aluminum, silicon, and iron. An increased incidence of respiratory disease has been reported in professional painters. Titanium is widely used as a pigment in the manufacturing of commercial paints. Cases of pneumoconiosis and alveolar proteinosis have been described in painters in which analysis of lung tissue revealed increased levels of titanium. This case is presented as an example of a rarely reported phenomenon, which may have clinical implications for evaluation and management of lung disease in painters.

[Systemic granulomatous disease, of the sarcoid type, caused by inhalation of titanium dioxide. Anatomo-clinical and experimental study]. / Doença granulomatosa sistémica, de tipo sarcoide, causada pela inalação de dióxido de titânio. Estudo anátomo-clínico e experimental.

Epithelioid granulomas, sarcoid type, are reported in four workers exposed to the inhalation of titanium dioxide dust. The granulomas were observed in the lungs, associated with respiratory insufficiency leading to death, in the hilum lymph nodes and liver. Diagnosis was done after a search of the occupational background of the patients followed by chemical and histochemical identification of the inhaled dusts within the lesions (morin and chromotropic acid methods and atomic absortion spectrophotometry) and experimental production of the disease in guinea-pigs. The harmful effects of titanium are not restricted to its dioxide, or to the inhalatory route. Different types of ceramic used in human implants and prostheses and the textile and aerospace industries use titanium.

Respiratory and nonrespiratory morbidity in a titanium oxide paint factory in Nigeria.

A study of 67 subjects in a small titanium oxide paint factory in Nigeria showed 50-54% frequency for airway symptoms, 20-40% for neurological symptoms, and 10-27% for other symptoms. The symptoms were well correlated with exposure (p less than .05) and pulmonary function tests (PFTs). The directly exposed subjects had likelihood odds ratios of 5 to 17 of presenting symptoms compared to controls. The PFT deficit, relative to the expected value, was significantly higher for those with airway symptoms than for those of other symptom categories (p less than .005). There were 28 (42%) cases of restrictive lung impairment. Exposure to cotton dust had confounding influence on the PFT of subjects previously exposed. Smoking rate was very low. These findings indicate the need for worker protection in a manufacturing plant in Nigeria.

Enzymes in lung lavage fluid after inhalation exposure to silica dust.

Lactate dehydrogenase (LDH) and lysosomal enzyme activity were measured in lung lavage fluid of guinea pigs exposed for 3 weeks to different concentrations of silica dust. Eight weeks and later after cessation of exposure, the amounts of N-acetyl-beta-D-glucosaminidase, cathepsin D, acid phosphatase, and LDH were increased. It is suggested that this increase indicates cell damage to alveolar macrophages, and that the enzyme changes are of relevance to determine the risk for pulmonary fibrosis caused by airborne substances.