Particulate Cobalt Research Articles

Spatial and seasonal distribution of dissolved and particulate bioactive metals in Antarctic sea ice

Iron (Fe) has been shown to limit growth of marine phytoplankton in the Southern Ocean, regulating phytoplankton productivity and species composition, yet does not seem to limit primary productivity in Antarctic sea ice. Little is known, however, about the potential impact of other metals in controlling sea-ice algae growth. Here, we report on the distribution of dissolved and particulate cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and zinc (Zn) concentrations in sea-ice cores collected during 3 Antarctic expeditions off East Antarctica spanning the winter, spring, and summer seasons. Bulk sea ice was generally enriched in particulate metals but dissolved concentrations were similar to the underlying seawater. These results point toward an environment controlled by a subtle balance between thermodynamic and biological processes, where metal availability does not appear to limit sea-ice algal growth. Yet the high concentrations of dissolved Cu and Zn found in our sea-ice samples raise concern about their potential toxicity if unchelated by organic ligands. Finally, the particulate metal-to-phosphorus (P) ratios of Cu, Mn, Ni, and Zn calculated from our pack ice samples are higher than values previously reported for pelagic marine particles. However, these values were all consistently lower than the sea-ice Fe:P ratios calculated from the available literature, indicating a large accumulation of Fe relative to other metals in sea ice. We report for the first time a P-normalized sea-ice particulate metal abundance ranking of Fe >> Zn ≈ Ni ≈ Cu ≈ Mn > Co ≈ Cd. We encourage future sea-ice work to assess cellular metal quotas through existing and new approaches. Such work, together with a better understanding of the nature of ligand complexation to different metals in the sea-ice environment, would improve the evaluation of metal bioavailability, limitation, and potential toxicity to sea-ice algae.

Metal-Specific Biomaterial Accumulation in Human Peri-Implant Bone and Bone Marrow.

Metallic implants are frequently used in medicine to support and replace degenerated tissues. Implant loosening due to particle exposure remains a major cause for revision arthroplasty. The exact role of metal debris in sterile peri‐implant inflammation is controversial, as it remains unclear whether and how metals chemically alter and potentially accumulate behind an insulating peri‐implant membrane, in the adjacent bone and bone marrow (BM). An intensively focused and bright synchrotron X‐ray beam allows for spatially resolving the multi‐elemental composition of peri‐implant tissues from patients undergoing revision surgery. In peri‐implant BM, particulate cobalt (Co) is exclusively co‐localized with chromium (Cr), non‐particulate Cr accumulates in the BM matrix. Particles consisting of Co and Cr contain less Co than bulk alloy, which indicates a pronounced dissolution capacity. Particulate titanium (Ti) is abundant in the BM and analyzed Ti nanoparticles predominantly consist of titanium dioxide in the anatase crystal phase. Co and Cr but not Ti integrate into peri‐implant bone trabeculae. The characteristic of Cr to accumulate in the intertrabecular matrix and trabecular bone is reproducible in a human 3D in vitro model. This study illustrates the importance of updating the view on long‐term consequences of biomaterial usage and reveals toxicokinetics within highly sensitive organs.

The Role of External Inputs and Internal Cycling in Shaping the Global Ocean Cobalt Distribution: Insights From the First Cobalt Biogeochemical Model.

Cobalt is an important micronutrient for ocean microbes as it is present in vitamin B12 and is a co‐factor in various metalloenzymes that catalyze cellular processes. Moreover, when seawater availability of cobalt is compared to biological demands, cobalt emerges as being depleted in seawater, pointing to a potentially important limiting role. To properly account for the potential biological role for cobalt, there is therefore a need to understand the processes driving the biogeochemical cycling of cobalt and, in particular, the balance between external inputs and internal cycling. To do so, we developed the first cobalt model within a state‐of‐the‐art three‐dimensional global ocean biogeochemical model. Overall, our model does a good job in reproducing measurements with a correlation coefficient of >0.7 in the surface and >0.5 at depth. We find that continental margins are the dominant source of cobalt, with a crucial role played by supply under low bottom‐water oxygen conditions. The basin‐scale distribution of cobalt supplied from margins is facilitated by the activity of manganese‐oxidizing bacteria being suppressed under low oxygen and low temperatures, which extends the residence time of cobalt. Overall, we find a residence time of 7 and 250 years in the upper 250 m and global ocean, respectively. Importantly, we find that the dominant internal resupply process switches from regeneration and recycling of particulate cobalt to dissolution of scavenged cobalt between the upper ocean and the ocean interior. Our model highlights key regions of the ocean where biological activity may be most sensitive to cobalt availability.

The acceleration of dissolved cobalt's ecological stoichiometry due to biological uptake, remineralization, and scavenging in the Atlantic Ocean

Abstract. The stoichiometry of biological components and their influence on dissolved distributions have long been of interest in the study of the oceans. Cobalt has the smallest oceanic inventory of inorganic micronutrients and hence is particularly vulnerable to influence by internal oceanic processes including euphotic zone uptake, remineralization, and scavenging. Here we observe not only large variations in dCo : P stoichiometry but also the acceleration of those dCo : P ratios in the upper water column in response to several environmental processes. The ecological stoichiometry of total dissolved cobalt (dCo) was examined using data from a US North Atlantic GEOTRACES transect and from a zonal South Atlantic GEOTRACES-compliant transect (GA03/3_e and GAc01) by Redfieldian analysis of its statistical relationships with the macronutrient phosphate. Trends in the dissolved cobalt to phosphate (dCo : P) stoichiometric relationships were evident in the basin-scale vertical structure of cobalt, with positive dCo : P slopes in the euphotic zone and negative slopes found in the ocean interior and in coastal environments. The euphotic positive slopes were often found to accelerate towards the surface and this was interpreted as being due to the combined influence of depleted phosphate, phosphorus-sparing (conserving) mechanisms, increased alkaline phosphatase metalloenzyme production (a zinc or perhaps cobalt enzyme), and biochemical substitution of Co for depleted Zn. Consistent with this, dissolved Zn (dZn) was found to be drawn down to only 2-fold more than dCo, despite being more than 18-fold more abundant in the ocean interior. Particulate cobalt concentrations increased in abundance from the base of the euphotic zone to become ∼ 10 % of the overall cobalt inventory in the upper euphotic zone with high stoichiometric values of ∼ 400 µmol Co mol−1 P. Metaproteomic results from the Bermuda Atlantic Time-series Study (BATS) station found cyanobacterial isoforms of the alkaline phosphatase enzyme to be prevalent in the upper water column, as well as a sulfolipid biosynthesis protein indicative of P sparing. The negative dCo : P relationships in the ocean interior became increasingly vertical with depth, and were consistent with the sum of scavenging and remineralization processes (as shown by their dCo : P vector sums). Attenuation of the remineralization with depth resulted in the increasingly vertical dCo : P relationships. Analysis of particulate Co with particulate Mn and particulate phosphate also showed positive linear relationships below the euphotic zone, consistent with the presence and increased relative influence of Mn oxide particles involved in scavenging. Visualization of dCo : P slopes across an ocean section revealed hotspots of scavenging and remineralization, such as at the hydrothermal vents and below the oxygen minimum zone (OMZ) region, respectively, while that of an estimate of Co* illustrated stoichiometrically depleted values in the mesopelagic and deep ocean due to scavenging. This study provides insights into the coupling between the dissolved and particulate phase that ultimately creates Redfield stoichiometric ratios, demonstrating that the coupling is not an instantaneous process and is influenced by the element inventory and rate of exchange between phases. Cobalt's small water column inventory and the influence of external factors on its biotic stoichiometry can erode its limited inertia and result in an acceleration of the dissolved stoichiometry towards that of the particulate phase in the upper euphotic zone. As human use of cobalt grows exponentially with widespread adoption of lithium ion batteries, there is a potential to affect the limited biogeochemical inertia of cobalt and its resultant ecology in the oceanic euphotic zone.

The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells

Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder. As patients with failed hip implants show increased urinary and blood cobalt levels, no studies have considered the effects of cobalt on human urothelial cells. Accordingly, we investigated the cytotoxic and genotoxic effects of particulate and soluble cobalt in urothelial cells. Exposure to both particulate and soluble cobalt resulted in a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ions. Based on intracellular cobalt ion levels, we found, when compared to particulate cobalt, soluble cobalt was more cytotoxic, but induced similar levels of genotoxicity. Interestingly, at similar intracellular cobalt ion concentrations, soluble cobalt induced cell cycle arrest indicated by a lack of metaphases not observed after particulate cobalt treatment. These data indicate that cobalt compounds are cytotoxic and genotoxic to human urothelial cells and solubility may play a key role in cobalt-induced toxicity.

The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung epithelial cells.

Cobalt is a toxic metal used in various industrial applications leading to adverse lung effects by inhalation. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells, especially normal lung epithelial cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in normal primary human lung epithelial cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble and particulate cobalt induced similar cytotoxicity while soluble cobalt was more genotoxic than particulate cobalt. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung epithelial cells.

Contrasting biogeochemical cycles of cobalt in the surface western Atlantic Ocean

AbstractDissolved cobalt (DCo; <0.2 µm; 14 to 93 pM) and the apparent particulate cobalt (PCo; >0.2 µm; <1 to 15 pM) were determined in the upper water column (<1000 m) of the western Atlantic Ocean along the GEOTRACES‐A02 section (64°N to 50°S). The lowest DCo concentrations, typical of a nutrient‐type distribution were observed in surface waters of the subtropical domains. Strong linear relationships between DCo and phosphate (P) as well as meridional gradients of decreasing DCo from high latitudes were characterized and both linked to the Co biological requirement. External sources such as the Amazon and the atmospheric deposition were found to contribute significantly (>10%) to the DCo stock of the mixed layer in the equatorial and north subtropical domains. Biotic and abiotic processes as well as the physical terms involved in the biogeochemical cycle of Co were defined and estimated. This allowed establishing the first global budget of DCo for the upper 100 m in the western Atlantic. The biological DCo uptake flux was the dominant sink along the section, as reflected by the overall nutrient‐type behavior of DCo. The regeneration varied widely within the different biogeochemical domains, accounting for 10% of the DCo‐uptake rate in the subarctic gyre and for up to 85% in southern subtropical domain. These findings demonstrated that the regeneration is likely the prevailing source of DCo in the surface waters of the western Atlantic, except in the subpolar domains where physically driven sources can sustain the DCo biological requirement.

The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity.

Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells

BackgroundThe mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co3O4).MethodsThis study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry.ResultsOur study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity.ConclusionsCobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity.

Total-body Exposure to Metal Sensitizers: Inhalation, Ingestion, and Skin Contact

O-30A6-4 Background/Aims: Exposures to sensitizing metals are a significant public and occupational health problem. Once sensitized, a person must avoid repeated exposures to specific metal(s) to prevent elicitation of adverse responses. Exposures may occur via inhalation, ingestion, and skin contact, with each pathway contributing to the total-body insult. The purpose of this study was to evaluate the solubility and absorption potential of 2 model metal allergens, cobalt, and beryllium, in the lung, gastrointestinal, and skin compartments. Methods: Solubility of cobalt and beryllium metal particles was evaluated using 1 or more biologically relevant artificial solvents: lung airway lining fluid, lung alveolar macrophage phagolysosomal fluid, gastrointestinal fluid, and skin sweat. Solubility tests provided estimates of bioaccessibility (amount available for absorption). Absorption across biological barriers was estimated using published human and animal toxicology literature. Results: Dissolution rates for cobalt metal particles, in units of g/(cm2 × day), were fastest in gastrointestinal fluid (3.7 ± 1.6 × 10 − 4) and slower in skin sweat (4.4 ± 0.4 × 10 − 5), lung alveolar macrophage phagolysosomal fluid (2.8 ± 0.8 × 10 − 5), and airway lining fluid (1.0 ± 0.3 × 10 − 5). For beryllium metal particles, dissolution rates were fastest in gastrointestinal fluid (4.1 ± 0.2 × 10 − 7) and slower in phagolysosomal fluid (1.1 ± 1.4 × 10 − 7), skin sweat (1.7 ± 0.6 × 10 − 8), and airway lining fluid (1.5 ± 0.8 × 10 − 9). Literature indicates the absorption of particulate cobalt compounds is 30% via inhalation, 3% to 50% via ingestion, and 0.024% and 3.6% via intact and abraded skin, respectively. Absorption of particulate beryllium compounds is <1% via ingestion. In the absence of inhalation and skin absorption values for particulate beryllium, levels were assumed to be similar to divalent cations such as cobalt. Conclusion: Cobalt and beryllium metal particles are soluble in biological fluids and may be absorbed via multiple exposure pathways. Based on the range of absorption values among biological compartments, systemic dose may be limited by dissolution rates.

Particulate cobalt and soluble cobalt: Same metal but different toxicities as assessed by cellular biology and innovative proteomic approaches

Particulate cobalt and soluble cobalt: Same metal but different toxicities as assessed by cellular biology and innovative proteomic approaches

Inhibition of proteasome activity is involved in cobalt-induced apoptosis of human alveolar macrophages.

Inhalation of particulate cobalt has been known to induce interstitial lung disease. There is growing evidence that apoptosis plays a crucial role in physiological and pathological settings and that the ubiquitin-proteasome system is involved in the regulation of apoptosis. Cadmium, the same transitional heavy metal as cobalt, has been reported to accumulate ubiquitinated proteins in neuronal cells. On the basis of these findings, we hypothesized that cobalt would induce apoptosis in the lung by disturbance of the ubiquitin-proteasome pathway. To evaluate this, we exposed U-937 cells and human alveolar macrophages (AMs) to cobalt chloride (CoCl(2)) and examined their apoptosis by DNA fragmentation assay, 4',6-diamidino-2'-phenylindol dihydrochloride staining, and Western blot analysis. CoCl(2) induced apoptosis and accumulated ubiquitinated proteins. Exposure to CoCl(2) inhibited proteasome activity in U-937 cells. Cobalt-induced apoptosis was mediated via mitochondrial pathway because CoCl(2) released cytochrome c from mitochondria. These results suggest that cobalt-induced apoptosis of AMs may be one of the mechanisms for cobalt-induced lung injury and that the accumulation of ubiquitinated proteins might be involved in this apoptotic process.

Temporal and spatial variability of cobalt in the Atlantic Ocean

The spatial and temporal variability of cobalt in the Atlantic Ocean was investigated by means of adsorptive cathodic stripping voltammetry. A vertical profile of total dissolved cobalt at the Bermuda Atlantic Time Series station ranged from 17 to 73 pM and displayed surface depletion indicative of biological utilization. This profile when compared with a cobalt profile from the northeast Pacific shows no increase in deep-water concentrations with thermohaline circulation through the deep ocean basins. Moreover, the middepth maximum observed in northeast Pacific profiles is not present in the Sargasso Sea, perhaps because of the lack of cobalt scavenging by particulate manganese oxides in surface waters and to the absence of a suboxic oxygen minimum zone, which, if present, could dissolve the manganese oxides.Total dissolved cobalt measurements were also made on a surface transect from the Sargasso Sea to coastal Massachusetts, USA, and on time-series samples from the Moored In Situ Trace Element Serial Sampler. Dissolved cobalt on this transect correlated strongly with salinity (r2 = 0.93) and ranged from 19 to 133 pM, indicating mixing of cobalt from shelf waters into the Sargasso Sea. Time-series samples near Bermuda did not show an obvious response to the summer maximum in aeolian dust deposition, with an annual average of 20 ± 10 pM at 40- to 47-m depths. By use of this annual value and particulate cobalt data from the literature, 100-m surface-water residence times were calculated to be as low as 0.32 yr for cobalt. Several sharp decreases in cobalt were observed in the time series that occurred simultaneously with a shallowing of the thermocline depth. These decreases could be caused by nutrient drawdown associated with higher productivity mesoscale eddy events.A west-east surface transect across the South Atlantic showed high cobalt concentrations at the boundaries of the transect and low concentrations in the center despite the high precipitation rates in the intertropical convergence zone. Phosphate measurements showed the similar trends as the total cobalt transect. A regression of cobalt vs. phosphate reveals a slope that is an order of magnitude higher than that of the northeast Pacific and that is similar to the slopes observed for zinc vs. phosphate in the Pacific.

Rapid thermal processing of magnetic materials using broad-band and laser radiation

Comparison is made between results achieved using two very different heating sources in in-vacuum rapid thermal processing systems. One system uses multiple quartz halogen bulbs (4 kW) whilst the second employs a rastered 60 W CO 2 laser. Sputtered thin films of the Heusler alloy PtMnSb and cobalt nitride precursor films subsequently processed to produce a particulate cobalt recording media provide examples.

Effect of particulate cobalt, chromium and cobalt-chromium alloy on human osteoblast-like cells in vitro

Effect of particulate cobalt, chromium and cobalt-chromium alloy on human osteoblast-like cells in vitro

THE EFFECTS OF PARTICULATE COBALT, CHROMIUM AND COBALT-CHROMIUM ALLOY ON HUMAN OSTEOBLAST-LIKE CELLS IN VITRO

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo.

Acute inflammatory lung injury retards pulmonary particle clearance

The deposition, retention, and clearance of inhaled cobalt oxide particles from the lungs of calves with acute inflammatory lung injury induced by parainfluenza-3 virus (PI-3) were examined. Acute pulmonary inflammation was induced by nebulization with 10(9) TCID50 of PI-3 virus on two successive days, and animals were subsequently exposed to an aerosol of particulate cobalt oxide (geometric mean diameter 0.54-0.65 microns) seven days post-virus infection (dpi). Pulmonary lesions at 7 dpi were typical of PI-3 pneumonitis and were characterized by patchy aveolitis and bronchiolitis with accumulations of neutrophils, macrophages, fibrin, and inflammatory debris. Calves were killed at 0, 7, and 21 days post-aerosol exposure (dpe) to evaluate particle clearance and retention by assay for cobalt in lung tissues, bronchoalveolar washings, and tracheobronchial lymph nodes. Control animals had a typically biphasic clearance pattern with rapid initial clearance of 50% of the initial lung burden (ILB) by 7 dpe followed by slower prolonged clearance. Clearance was significantly retarded (P less than 0.05) in calves with viral-induced acute inflammatory lung injury; 90% of the ILB was retained at 7 dpe. Essentially all particles recoverable by bronchoalveolar lavage were intracellular within pulmonary alveolar macrophages (PAM) in both experimental and control groups, but interstitial sequestration of particles within PAM was commonly observed only in the lungs of calves with viral pneumonitis. Pneumonic calves also exhibited retarded translocation of particles to regional lymph nodes. The results document impaired particulate clearance from acutely inflamed lungs, and implicate decreased mucociliary clearance and interstitial sequestration within PAM as the major contributing factors. These functional alterations would be expected to enhance the progression of virus-induced acute pulmonary inflammatory injury.

In Reply: Exposure to Hard Metal

In my recent editorial, I offered the scientifically conservative view that the cause of the parenchymal lung disorders which have been associated with exposure to hard metal (tungsten carbide with binders including cobalt) remains uncertain. Dr. Abraham, citing some of his own work and the classic inhalation studies at Saranac Lake, 1 Schepers GWH The biologic action of particulate cobalt metal. AMA Arch Indust Health. 1955; 12: 127-133 PubMed Google Scholar argues that the pathogenic role of cobalt has been established. His basis for this is the similarity between histologically distinct giant cell reactions seen in some reported cases of hard metal disease and the pathologic response to cobalt metal dust reported by Schepers. 1 Schepers GWH The biologic action of particulate cobalt metal. AMA Arch Indust Health. 1955; 12: 127-133 PubMed Google Scholar Exposure to Hard MetalCHESTVol. 87Issue 4PreviewTo the Editor: Full-Text PDF

The toxicity of metals used in orthopaedic prostheses. An experimental study using cultured human synovial fibroblasts

Some of the component metals of the alloys used for total joint prostheses are toxic and dissolve in the body fluids. It is important to establish how toxic these metals are and to assess the risk of localised tissue necrosis around the prostheses. This has been investigated by incubating primary monolayer cultures of human synovial fibroblasts with various preparations of metals for periods up to 18 days. Morphological changes were evident after exposure to cobalt chloride at a concentration of 50 nanomoles per millilitre and to nickel chloride at 200 nanomoles per millilitre. Chromic chloride, ammonium molybdate and ferric chloride produced no changes up to 500 nanomoles per millilitre. Cultures exposed to particulate pure metals were poisoned by cobalt and vanadium but were not affected under the same conditions by nickel, chromium, molybdenum, titanium or aluminium. Particulate cobalt and vanadium were probably toxic due to their relatively high solubility (four and one micromoles per millilitre respectively after seven days incubation). Particulate nickel also dissolved (three nanomoles per millilitre after seven days) but not in sufficient quantities to be toxic. It appears, therefore, that potentially the most harmful components are cobalt from cobalt-chromium alloy, nickel from stainless steel, and vanadium from titanium alloy. As far as can be estimated, the only combination of materials which is likely to give rise to toxic levels of metal under clinical conditions, is cobalt-chromium alloy articulating against itself to produce relatively high levels of cobalt.

A STUDY ON THE EFFECTS OF PARTICULATE METALS OF ORTHOPAEDIC INTEREST ON MURINE MACROPHAGES IN VITRO

This is part of a larger study designed to investigate the action of particulate metals of orthopaedic interest on tissues. Damaging effects were determined by cytological examination and the assay of two enzymes. Lactic dehydrogenase (LDH) if released into the supernatant indicates a damaged cell membrane; decreased intracellular levels of glucose-6-phosphate dehydrogenase (G6PD) indicates a lowered phagocytic capacity of the cells. Soluble and wear products around implanted prostheses could facilitate late infections by impairing local reactions to bacteria. Particulate cobalt, nickel and cobalt-chromium alloy were found to damage the cells and to cause LDH release. G6PD was found to have a lower activity in the cells exposed to these materials. In contrast, titanium, chromium and molybdenum were well tolerated by macrophages and had no effect on the distribution and activity of either enzyme. The solubility of these metals in the culture medium was also measured.