Carcinogenic hazard assessment of cobalt-containing alloys in medical devices: Review of in vivo studies.

Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices. The purpose of this review is to present a comprehensive assessment of the available in vivo preclinical data on the carcinogenic hazard potential of exposure to Co-containing alloys (CoCA) in medical devices by relevant routes. In vivo data were reviewed from 33 preclinical studies that examined the impact of Co exposure on local and systemic tumor incidence in rats, mice, guinea pigs, and hamsters. Across these studies, there was no significant increase of local or systemic tumors in studies relevant for medical devices. Taken together, the relevant in vivo data led to the conclusion that CoCA in medical devices are not a carcinogenic hazard in available in vivo models. While specific patient and implant factors cannot be fully replicated using in vivo models, the available in vivo preclinical data support that CoCA in medical devices are unlikely a carcinogenic hazard to patients.

Mortality Among Hardmetal Production Workers: Swedish Measurement Data and Exposure Assessment.

BACKGROUND: Mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry. Exposure assessment for cobalt is presented. METHODS: A historical database (1970 to 2012) of personal and area measurements of cobalt, tungsten, and nickel in the Swedish hardmetal industry was created. Log linear and exponential modeling of cobalt concentrations based on time period, job, and site was performed, and cumulative and mean exposures were calculated. RESULTS: Some 37% of the personal cobalt measurements exceeded 0.02 mg/m, mostly for powder production, pressing, and shaping. The log linear regression showed statistical differences (P < 0.05) between sites, time periods, and jobs. Some 1.6% of the cobalt cumulative exposures for blue-collar workers exceeded 0.4 mg/m years. CONCLUSION: Low levels of cumulative and mean exposures were determined.

Metal release from stainless steel powders and massive sheets--comparison and implication for risk assessment of alloys.

Industries that place metal and alloy products on the market are required to demonstrate that they are safe for all intended uses, and that any risks to humans, animals or the environment are adequately controlled. This requires reliable and robust in vitro test procedures. The aim of this study is to compare the release of alloy constituents from stainless steel powders of different grades (focus on AISI 316L) and production routes into synthetic body fluids with the release of the same metals from massive sheets in relation to material and surface characteristics. The comparison is justified by the fact that the difference between massive surfaces and powders from a metal release/dissolution and surface perspective is not clearly elucidated within current legislations. Powders and abraded and aged (24 h) massive sheets were exposed to synthetic solutions of relevance for biological settings and human exposure routes, for periods of up to one week. Concentrations of released iron, chromium, nickel, and manganese in solution were measured, and the effect of solution pH, acidity, complexation capacity, and proteins elucidated in relation to surface oxide composition and its properties. Implications for risk assessments based on in vitro metal release data from alloys are elucidated.

Characterization and assessment of dermal and inhalable nickel exposures in nickel production and primary user industries.

The aim of this study was to measure the levels of nickel in the skin contaminant layer of workers involved in specific processes and tasks within the primary nickel production and primary nickel user industries. Dermal exposure samples were collected using moist wipes to recover surface contamination from defined areas of skin. These were analysed for soluble and insoluble nickel species. Personal samples of inhalable dust were also collected to determine the corresponding inhalable nickel exposures. The air samples were analysed for total inhalable dust and then for soluble, sulfidic, metallic, and oxidic nickel species. The workplace surveys were carried out in five different workplaces, including three nickel refineries, a stainless steel plant, and a powder metallurgy plant, all of which were located in Europe. Nickel refinery workers involved with electrolytic nickel recovery processes had soluble dermal nickel exposure of 0.34 microg cm(-2) [geometric mean (GM)] to the hands and forearms. The GM of soluble dermal nickel exposure for workers involved in packing nickel salts (nickel chloride hexahydrate, nickel sulphate hexahydrate, and nickel hydroxycarbonate) was 0.61 microg cm(-2). Refinery workers involved in packing nickel metal powders and end-user powder operatives in magnet production had the highest dermal exposure (GM = 2.59 microg cm(-2) soluble nickel). The hands, forearms, face, and neck of these workers all received greater dermal nickel exposure compared with the other jobs included in this study. The soluble nickel dermal exposures for stainless steel production workers were at or slightly above the limit of detection (0.02 microg cm(-2) soluble nickel). The highest inhalable nickel concentrations were observed for the workers involved in nickel powder packing (GM = 0.77 mg m(-3)), although the soluble component comprised only 2% of the total nickel content. The highest airborne soluble nickel exposures were associated with refineries using electrolytic processes for nickel recovery (GM = 0.04 mg m(-3) total nickel, containing 82% soluble nickel) and those jobs involving contact with soluble nickel compounds (GM = 0.02 mg m(-3) total nickel content, containing 76% soluble nickel). The stainless steel workers were exposed to low concentrations of relatively insoluble airborne nickel species (GM = 0.03 mg m(-3) total nickel, containing 1% soluble nickel). A statistically significant correlation was observed between dermal exposures for all anatomical areas across all tasks. In addition, the dermal and inhalable (total) nickel exposures were similarly associated. Overall, dermal exposures to nickel, nickel compounds, and nickel alloys were relatively low. However, exposures were highly variable, which can be explained by the inconsistent use of personal protective equipment, varying working practices, and different standards of automation and engineering controls within each exposure category.

Predicting graded young modulus values of Ti alloys modified by ion implantation.

There has been, and is still, concern about the high elastic modulus of Ti alloys compared to bone. Any reduction in the Young's modulus value of the implant is expected to enhance stress redistribution to the adjacent bone tissues, minimize stress shielding and eventually prolong device lifetime. Dynamic Monte Carlo simulation is used to predict the gradual reduction in Young's modulus values between the bulk of Ti alloys and the modified surface layers due to Ca ion implantation. The simulation can be used as a screening step when applying new alloys and/or coatings.

Surface area of respirable beryllium metal, oxide, and copper alloy aerosols and implications for assessment of exposure risk of chronic beryllium disease.

The continued occurrence of chronic beryllium disease (CBD) suggests the current occupational exposure limit of 2 microg beryllium per cubic meter of air does not adequately protect workers. This study examined the morphology and measured the particle surface area of aerodynamically size-separated powders and process-sampled particles of beryllium metal, beryllium oxide, and copper-beryllium alloy. The beryllium metal powder consisted of compact particles, whereas the beryllium oxide powder and particles were clusters of smaller primary particles. Specific surface area (SSA) results for all samples (N=30) varied by a factor of 37, from 0.56 +/- 0.07 m(2)/g (for the 0.4-0.7 microm size fraction of the process-sampled reduction furnace particles) to 20.8 +/- 0.4 m(2)/g (for the 6 microm) to 20.8 +/- 0.44 m(2)/g (for the particle size fraction

Crystallographic orientation assessment by electron backscattered diffraction.

With an angular orientation accuracy of at least 1 , the ability of electron backscattered diffraction (EBSD) to determine and emphasise crystallographic orientation is illustrated. Using the abilities of specially developed software for computing Euler angles derived from the scanned specimen, misorientations are pointed out with acceptable flexibility and graphic output through crystallographic orientation maps or pole figures. This ability is displayed in the particular case of laser cladding of nickel-based superalloy, a process that combines the advantages of a near net-shape manufacturing and a close control of the solidification microstructure (E-LMF: epitaxial laser metal forming).